Request History

• Restore to current request
• applications/index/page:5/sort:protocol_no/direction:asc/trial_therapeutic_confirmatory:1
• applications/index/page:5/sort:study_title/direction:asc/trial_therapeutic_confirmatory:1
• applications/view/612
• applications/view/206

Session

• Config(array)
  • userAgent9c3d2c89526db53b7b69e8c9faa06145
  • time1763659669
  • countdown10

Request

Cake Params

• plugin(null)
• controllerapplications
• actionindex
• named(array)
  • page24
  • sortstudy_title
  • directionasc
  • trial_therapeutic_confirmatory1
• pass(empty)
• isAjax(false)
• paging(array)
  • Application(array)
    • page24
    • current5
    • count205
    • prevPage(true)
    • nextPage(true)
    • pageCount41
    • order(array)
      • Application.study_titleasc
    • limit5
    • options(array)
      • page24
      • order(array)
        • Application.study_titleasc
      • sortstudy_title
      • directionasc
    • paramTypenamed

Post data

• Application(array)
  • trial_therapeutic_confirmatory1

Query string

No querystring data.

Cookie

To view Cookies, add CookieComponent to Controller

Current Route

• keys(array)
  • 0controller
  • 1action
• options(empty)
• defaults(array)
  • plugin(null)
• template/:controller/:action/*

Sql Logs

Logs

View Variables

• trial_statuses(array)
  • 1Recruiting
  • 2Not yet recruiting
  • 3Suspended
  • 4Stopped
  • 5Completed
  • 6In follow-up
  • 7Analysing
  • 8Writing-up
  • 9Application withdrawn
• applications(array)
  • 0(array)
    • Application(array)
      • id1256
      • user_id263
      • trial_status_id5
      • abstract_of_study<p>\n COVID-19 pandemic has caused global suffering, mortality, and severe economic pressures. New variants of SARS-CoV-2 have been identified some of which increase the load of virus shed from an infected person, resulting in an increase in viral transmission and potentially severity of illness. There is no proven COVID-19 treatment for people who are not sick enough to be hospitalized. There is an urgent need to rapidly assess treatments in an outpatient setting, to prevent disease progression, and reduce serious complications or death. This trial will be a Phase-3, multi-center, randomized, double-blind, to evaluate safety and efficacy of S-217622 versus placebo among a global sample of approximately 1490 (745 on S-217622 and 745 on placebo) will be randomized into the study. Outpatient adults ( ≥ 18 years) with: a) documented positive SARS-CoV-2 nucleic acid or antigen test from a sample collected ≤120 hours (5 days) prior to randomization, b) onset of symptoms of COVID-19 ≤ 5 days prior to randomization, c) presence of 1 or more select COVID-19 symptoms within 24 hours prior to randomization. Participants will be eligible regardless of vaccination status and will be classified as either high risk or low risk. High-risk participants: defined as aged ≥65 years or those with presence of highrisk conditions. Low-risk participants: defined as those not meeting the high-risk definition. We target to initially enrol about 100 participants, but this will depend on how quickly the enrolment target is reached across all sites. Participants will be randomized into the study using an IRT, and stratified by geographic region, regardless of COVID-19 vaccination status. Participants’ demographics will be collected, medical history and physical examination done, vital signs and lab tests conducted as well as adverse events reported. The main intent of the ACTIV-2d/A5407 study is to evaluate the efficacy of S-217622 vs. placebo. The study will be conducted in the setting of locally available standard of care COVID-19 treatment. High-risk and low-risk participants will be analyzed together for the primary analysis and separately for secondary analyses. There will be safety analyses, which will be analyzed in the Safety population, and pharmacokinetic (PK) analyses, which will be analyzed in the PK population. The study duration will be from days 1 through 29 intensive study, followed by limited study through 24 weeks.</p>\n
      • study_title<p>\n A Phase 3, multicenter, randomized, double-blind, 24-week study of the clinical and antiviral effect of S-217622 compared with placebo in non-hospitalized participants with COVID-19</p>\n
      • laymans_summary<p>\n The COVID-19 outbreak in the human population was first reported in Wuhan City, Hubei Province, China in December 2019. The rapid increase in the number of cases led to a declaration by the World Health Organization (WHO) on 11 March 2020 that the disease had spread to the whole world. As of May 2, 2021, the virus had been detected in more than 200 countries and infected more than 151 million people, causing more than 3.1 million deaths worldwide. In Kenya, as of May 10, 2021, more than 163 thousand cases and over 2,900 deaths had been reported. The signs and symptoms of COVID-19 presents differently in people. In the majority of people who are infected, it is mild, or the person may not have any symptoms of sickness. However, among patients with symptoms, typical presentations include fever, cough, muscle aches and shortness of breath. More severe cases have difficulty in breathing requiring admission in a hospital and this results in death in some patients. For majority of people, it does not require treatment but symptoms such as tiredness and shortness of breath appear to persist up to 2 months even after the virus has cleared. Several vaccines against COVID-19 have become available for use, and vaccinations have been initiated in many countries for the older people and the ones at high risk like doctors and nurses. These vaccines appear to be effective in preventing COVID-19 but we currently don’t know if the vaccines will work well long-term. In many middle- or low-income countries like Kenya, there is a shortage in the supply of these vaccines and this is expected to remain the case well beyond 2021. Some treatment options like steroids for patients with severe disease requiring admission in hospital have become available. Still, new treatments that can be given early after infection to prevent disease progression and long-term complications are urgently needed. Recent studies show that the treatments are beneficial in patients treated within the first 7 days after symptoms starts, reducing the need for subsequent hospital and doct</p>\n
      • short_titleACTIV-2d/A5407
      • protocol_noECCT/23/04/03
      • version_noACTIV-2d/A5407 Version 3.0 23 Jun 2022
      • date_of_protocol30-06-2022
      • study_drugS-217622
      • disease_condition(SARS-CoV-2) Infection
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameS-217622
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantElizabeth Chirchir
      • declaration_date114-04-2023
      • declaration_principal_investigatorProf Abraham Siika
      • declaration_date214-04-2023
      • placebo_presentYes
      • study_objectives<p>\n <strong>1. STUDY OBJECTIVES</strong></p>\n<p>\n The main intent of the study is to evaluate the efficacy of S-217622 vs. placebo. The study will be conducted in the setting of locally available standard of care COVID-19 treatment. High-risk and low-risk participants will be analyzed together for the primary analysis and separately for secondary analyses. The following primary, secondary, and exploratory objectives will be addressed in the modified intent-to-treat (mITT) population, except for the safety analyses, which will be analyzed in the Safety population, and pharmacokinetic (PK) analyses, which will be analyzed in the PK population</p>\n<p>\n <strong>1.1. Primary Objective</strong></p>\n<p>\n To determine if S-217622 will reduce the time to sustained symptom resolution through Day 29. Time to sustained symptom resolution is defined as the time from start of study intervention to the first day of 4 consecutive days with complete resolution of 13 COVID-19 symptoms on participant self-assessment AND alive and without hospitalization for any reason by Day 29. Hospitalization is defined as ≥24 hours of acute care, in a hospital or similar acute care facility, including emergency rooms, urgent care clinics, or facilities instituted to address medical needs of those with COVID-19.</p>\n<p>\n <strong>1.2. Secondary Objectives</strong></p>\n<p>\n 1.2.1. Key secondary objective: To determine the effect of S-217622 compared with placebo on the change from baseline in quantitative log10 SARS-CoV-2 RNA levels by PCR on NP swab at Day 4. 1.2.2. Key secondary objective: To determine whether S-217622 reduces COVID-19- related hospitalization (adjudicated) and all deaths regardless of occurrence outside of hospital or during hospitalization (not adjudicated) through Day 29. 1.2.3. To determine if S-217622 will decrease the proportion of participants with detectable SARS-CoV-2 viral culture on NP swab at Day 4. 1.2.4. To explore differences between S-217622 and placebo in time to sustained symptom resolution through Day 29 among subgroups, including by high risk vs. low risk at enrollment, by COVID-19 vaccination status, by receipt of COVID-19 treatments, and by time from symptom onset at enrollment. 1.2.5. To explore differences between S-217622 and placebo in the proportion of participants with detectable SARS-CoV-2 by viral culture from NP swab at Day 4 among subgroups, including by high risk vs. low risk at enrollment, by COVID-19 vaccination status, by receipt of COVID-19 treatments, and by time from symptom onset at enrollment. 1.2.6. To determine whether S-217622 reduces all-cause hospitalization and all deaths regardless of occurring prior to hospitalization (not adjudicated) through Day 29. 1.2.7. To determine if S-217622 will decrease the proportion of participants with detectable SARS-CoV-2 by viral culture from NP swab at Day 8. 1.2.8. To determine the efficacy of S-217622 to increase the proportion of participants with NP SARS-CoV-2 RNA levels by quantitative polymerase chain reaction (PCR) below the lower limit of quantification (LLoQ) on Days 4 and 8. 1.2.9. To determine whether S-217622 reduces levels of SARS-CoV-2 RNA by quantitative PCR in NP swabs from participants on Days 4 and 8. 1.2.10. To determine whether S-217622 results in a shorter time to return to pre-COVID-19 health compared with placebo throughDay 29. 1.2.11. To evaluate the efficacy of S-217622 compared with placebo based on the assessment of symptoms using the World Health Organization (WHO) ordinal scale (1-8) (see Section 6.3.16). 1.2.12. To determine the efficacy of S-217622 to maintain pulse oximetry measurement of ≥96% through Day 29. 1.2.13. To evaluate the safety of S-217622. 1.2.14. To explore measures of psychological health, functional health, and health-related quality of life in participants through end of study follow-up (Week 24). 1.2.15. To determine whether S-217622 reduces death due to any cause through end of study follow-up (Week 24). 1.2.16. To determine the PK of S-217622. </p>\n<p>\n <strong>1.3. Exploratory Objectives</strong></p>\n<p>\n 1.3.1. To evaluate whether S-217622 reduces a COVID-19 Severity Ranking Scale score based on COVID-19-associated symptom burden (severity and duration), hospitalization, and death through Day 29. 1.3.2. To explore the impact of S-217622 on participant-reported rates of new SARS-CoV-2 positivity of household contacts through Day 29. 1.3.3. To explore whether baseline and follow-up laboratory markers are associated with clinical and virologic outcomes in relation to S-217622 use. 1.3.4. To explore baseline and emergent viral resistance to S-217622 through Day 16. 1.3.5. To explore differences between S-217622 and placebo in NP SARS-CoV-2 RNA levels among subgroups, including by high risk vs. low risk at enrollment, by COVID-19 vaccination status, by receipt of COVID-19 treatments, and by time from symptom onset at enrollment 1.3.6. To explore possible predictors of outcomes, including death and hospitalization, across the study population, including by time from symptom onset, symptoms at baseline, sex assigned at birth, demographic characteristics, geographic region, and vaccination status. 1.3.7. To explore and develop a model for the interrelationships between virologic outcomes and clinical outcomes in each study group. 1.3.8. To explore the association between viral genotypes and phenotypic susceptibility to S-217622 and clinical outcomes and virologic response to S-217622. 1.3.9. To explore the prevalence, severity, and types of persistent symptoms and clinical sequelae in participants through end-of-study follow-up (Week 24). 1.3.10. To explore relationships between exposure of S-217622 with laboratory markers and clinical outcomes. 1.3.11. To evaluate the safety of S-217622 in the high-risk and low-risk subpopulations. 1.3.12. To explore differences between S-217622 and placebo in death due to any cause through end of study follow-up (Week 24) in the high-risk and lowrisk subpopulations. 1.3.13. To explore the frequency of symptomatic viral rebound, defined as an increase in quantitative NP SARS-CoV-2 viral culture or NP SARS-CoV-2 RNA levels by quantitative PCR after Day 4 in the setting of new or worsening clinical symptoms, in both study groups. 1.3.14. To explore the frequency of viral rebound in both treatment arms, defined as an increase in quantitative NP SARSCoV-2 viral culture or NP SARS-CoV-2 RNA levels by quantitative PCR after Day 4. 1.3.15. To explore differences between S-217622 and placebo to reduce levels of SARS-CoV-2 RNA by quantitative PCR in NP swabs from participants on Days 4 and 8 among participants who have a positive culture at baselin</p>\n
      • principal_inclusion_criteria<p>\n <strong>Inclusion Criteria</strong></p>\n<p>\n For all participants</p>\n<p>\n 4.1.1.1. Ability and willingness of participant to provide informed consent prior to initiation of any study procedures. 4.1.1.2. Age ≥18 years. 4.1.1.3. Documentation of laboratory-confirmed active SARS-CoV-2 infection, as determined by a nucleic acid (e.g., reverse-transcriptase PCR) or antigen test from any respiratory tract specimen (e.g., oropharyngeal, NP or nasal swab, or saliva) collected ≤120 hours (5 days) prior to randomization. 4.1.1.4. Participants are expected to begin study intervention ≤5 days from self-reported date of onset of any of the COVID-19-related symptoms from the following list: ï‚· Cough ï‚· Shortness of breath or difficulty breathing ï‚· Feeling feverish ï‚· Chills ï‚· Fatigue ï‚· Body pain or muscle pain or aches ï‚· Diarrhea ï‚· Nausea ï‚· Vomiting ï‚· Headache ï‚· Sore throat ï‚· Nasal obstruction or congestion ï‚· Nasal discharge ï‚· Loss of taste or smell 4.1.1.5. One or more of the following signs/symptoms present within 24 hours prior to randomization (all criteria in Section 4.1.1.4 except loss of taste or smell): ï‚· Cough ï‚· Shortness of breath or difficulty breathing ï‚· Feeling feverish</p>\n<p>\n ï‚· Chills ï‚· Fatigue ï‚· Body pain or muscle pain or aches ï‚· Diarrhea ï‚· Nausea ï‚· Vomiting ï‚· Headache ï‚· Sore throat ï‚· Nasal obstruction or congestion ï‚· Nasal discharge 4.1.1.6. Oxygenation saturation of ≥92% on room air adjusted for altitude and obtained at rest by study staff within 24 hours prior to randomization. (See Manual of Procedures [MOP] for details of adjustments for altitude.) NOTE: For a potential participant who regularly receives chronic supplementary oxygen for an underlying lung condition, oxygen saturation measured while on their standard home oxygen supplementation level must be ≥92%. 4.1.1.7. Agrees to not participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 during the study period unless meeting hospitalization criteria or reaching Day 29, whichever is earliest. 4.1.1.8. For participants who are of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to randomization. Reproductive potential is defined as: ï‚· Participants who have reached menarche ï‚· Participants who have not been postmenopausal for at least 12 consecutive months with follicle-stimulating hormone (FSH) ≥40 IU/mL or 24 consecutive months if an FSH level is not available ï‚· Participants who have not undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or bilateral salpingectomy) Note: For individuals with permanent infertility due to an alternate medical cause (e.g., Mullerian agenesis, androgen insensitivity), investigator discretion should be applied to determining study entry and need for pregnancy testing. 4.1.1.9. Participants who are of reproductive potential who engage in sexual activity that may lead to pregnancy must agree to use effective contraception from study entry through 14 days after the last dose of study intervention. Effective methods of contraception includeï‚· Sexual abstinence ï‚· Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (e.g., oral, intravaginal, transdermal, injectable) PLUS an additional barrier method ï‚· Progestogen-only hormone contraceptive associated with inhibition of ovulation: oral, injectable PLUS an additional barrier method ï‚· Implanted progestogen-only contraceptives associated with inhibition of ovulation PLUS an additional barrier method ï‚· Intrauterine devices (with or without release of hormones) ï‚· Bilateral tubal occlusion (e.g., bilateral tubal ligation) ï‚· Vasectomized partner ï‚· Barrier methods that include male or female condom (cervical cap, diaphragm or sponge with spermicide) The investigator, in consultation with the participant, will confirm that the participant has selected an appropriate method of contraception. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a participant with an early undetected pregnancy. NOTE: Participants not of reproductive potential are eligible without requiring the use of a contraceptive method. Participant-reported history is acceptable documentation of surgical sterilization and menopause, including vasectomy in a sole partner. 4.1.1.10. Participants assigned female sex at birth who are of reproductive potential must agree not to donate eggs (ova, oocytes) for the purpose of reproduction from study entry through 14 days after the last dose of S-217622 or placebo. 4.1.1.11. Participants with pregnant partners must agree to use condoms during vaginal intercourse from study entry through 14 days after the last dose of S-217622 or placebo administration. NOTE: Participants are also strongly advised to inform their non-pregnant sexual partners of reproductive potential to use effective contraceptives (as described in Section 4.1.1.9) from study entry through 14 days after the last dose of study intervention is administered. 4.1.1.12. Participants assigned male sex at birth must agree to refrain from sperm donation from study entry through 14 days after the last dose of S-217622/placebo administration. 4.1.1.13. Participant is willing and able to comply with the study requirements and procedures as judged by the investigator</p>\n<p>\n  </p>\n<p>\n <strong>For high-risk participants (limited to 50% of enrollment</strong></p>\n<p>\n 15. Participants at high risk are defined as having 1 or more factors that lead to a higher risk of progression to severe COVID-19:</p>\n<p>\n  Participants at high risk are defined as having 1 or more factors that lead to a higher risk of progression to severe COVID-19: ï‚· Age ≥65 years ï‚· Age ≥18 with 1 of the following: o Obesity (body mass index [BMI] ≥30 kg/m2 ). Note: BMI is rounded to the nearest whole number, for example 29.5 kg/m2 is rounded to 30 kg/m2 . o Diabetes mellitus o Hypertension o Cardiovascular disease (including congenital heart disease) o Chronic lung disease (e.g., chronic obstructive pulmonary disease [COPD], moderate to severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension) o Chronic kidney disease, as long as the participant does not have known creatinine clearance (CrCl) <30 mL/min by Cockcroft-Gault or require dialysis (see Exclusion Criterion 4.1.2.9) o Down syndrome o Sickle cell disease o One of the following immunocompromising conditions or immunosuppressive treatments:  Receiving chemotherapy or other therapies for cancer  Hematologic malignancy (active or in remission)  History of a hematopoietic stem cell or a solid organ transplant  HIV infection: not on antiretroviral therapy or with CD4+ cell count <200 cells/mm3  Combined primary immunodeficiency disorder  Taking immunosuppressive medications (e.g., drugs to suppress rejection of transplanted organs or to treat rheumatologic and gastrointestinal conditions, such as anti-TNF agents, mycophenolate, and rituximab) Note: Current use of some corticosteroids is exclusionary, due to concern for possible DDI with S-217622. See Section 5.4.2 for prohibited medications.</p>\n<p>\n <strong>For low-risk participants (limited to 50% of enrollment)</strong></p>\n<p>\n Participants at low risk for progression to severe COVID-19 are defined as <65 years of age and with none of the risk factors in Inclusion Criterion4.1.1.14</p>\n
      • principal_exclusion_criteria<p>\n <strong>Exclusion Criteria</strong></p>\n<p>\n 1. History of hospitalization for the current SARS-CoV-2 infection (i.e., prior hospitalization for a prior episode of SARSCoV-2 infection is allowable). 2. For the current SARS-CoV-2 infection, any positive SARS-CoV-2 molecular (nucleic acid) or antigen test from any respiratory tract specimen (e.g., oropharyngeal, NP or nasal swab, or saliva) collected ˃120 hours (5 days) prior to randomization. Participants with reinfection, defined as prior SARS-CoV-2 infection that began >90 days prior to the current onset of symptoms with interval resolution of symptoms are eligible as long as the current infection has not been present for more than 5 days prior to randomization. 3. Current need for hospitalization or immediate medical attention in the opinion of the investigator. 4. Current use of any medications prohibited with the study intervention, as described in Section 5.4.2. Use of Paxlovid at any time and the use of any oral, inhaled, or injectable medication intended to treat symptomatic SARS-CoV-2 infection before enrollment are excluded. After enrollment, locally available SARS-CoV-2 treatment (including but not limited to molnupiravir, mAbs, outpatient IV remdesivir, convalescent plasma, inhaled budesonide, favipiravir, and fluvoxamine) will be permitted, as long as there are no concerns for DDIs as outlined in Section 5. Receipt of any investigational treatments for the current episode of SARS-CoV-2 at any time prior to randomization is exclusionary. NOTE: This does not include drugs approved for other uses and taken for those indications or COVID-19 vaccines. NOTE: Use of locally authorized or approved therapies to prevent COVID-19, such as mAbs given solely to prevent COVID-19, are not exclusionary. 6. Any comorbidity requiring surgery within 7 days prior to randomization or that is considered life threatening in the opinion of the investigator within 28 days prior to randomization. 7. Currently pregnant or breastfeeding. 8. Known allergy/sensitivity or any hypersensitivity to components of S-217622 or placebo for S-217622. 9. Known current renal impairment defined as CrCl <30 mL/min by Cockcroft-Gault or requiring dialysis. 10. Known history of cirrhosis or liver decompensation (including ascites, variceal bleeding, or hepatic encephalopathy)</p>\n
      • primary_end_points<p>\n The primary outcome measure is: Time in days from the start of S-217622 to sustained symptom resolution; the definition of sustained symptom resolution is the first of 4 consecutive days without symptoms (all targeted symptoms recorded as absent) and being alive and without hospitalization for any reason by Day 29.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong>SITE -714_ MOI UNIVERSITY CLINICAL RESEARCH CENTRE_Prof Abraham Siika </strong>I</p>\n<p>\n <strong>Study area</strong></p>\n<p>\n In 2004, the Moi University Clinical Research Centre (MUCRC) was founded as an international site of the Indiana University AIDS Clinical Trials Unit (ACTU), an affiliate of the AIDS Clinical Trials Group (ACTG) Network. Following two years of site preparation, trial A5208/OCTANE (Optimal Combination Therapy after Nevirapine Exposure) was initiated at the MUCRC in July 2006.In December 2006, Indiana University was defunded from the ACTG Network and the MUCRC reverted to the Division of AIDS (DAIDS) of the National Institutes of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), as a protocol-limited site. In December 2008, MUCRC became a site for the United States Military HIV Research Program (USMHRP) and continues to perform clinical trials for the ACTG Network. While MUCRC is a clinical trials site for the USMHRP, it operates under the auspices of the USAID – Academic Model Providing Access to Healthcare Research Network (AMPATH ResNet). AMPATH, founded in November 2001, is a collaboration between the Moi University School of Medicine (MUSoM), Moi Teaching and Referral Hospital (MTRH) and a network of North American Medical Schools (the AMPATH Consortium) led by Indiana University School of Medicine (IUSoM).</p>\n<p>\n <strong>Location</strong></p>\n<p>\n The MUCRC is located on the second floor of the Chandaria Cancer and Chronic Diseases Centre, Eldoret, Kenya. The CRS has the following areas/rooms: a waiting bay for patients; a nursing station (for consenting, vital signs measurements); a phlebotomy room; four clinical examination rooms; a pharmacy (including a separate cyctoxics preparation room) one data room; one office for the site coordinator, study coordinators and regulatory affairs officer. one office for quality Name of Site Physical address Contact details (tel.no, p.o box..) Contact person County Name of Site Physical address Contact details (tel.no, p.o box..) Contact person County Name of Site Physical address Contact details (tel.no, p.o box..) Contact person County Kenyatta National Hospital Kenyatta National Hospital P.O. Box 20723-00202 Dr John Kinuthia Nairobi City 5 Ahero Clinical Trials Unit, Ahero County Hospital, P.O. Box 54-40100 Dr Bernhards Ogutu Kisumu 6 KEMRI CCR – BUTERE SITE BUTERE COUNTY HOSPITAL P.O. Box 40-50101 Dr Janet Oyieko Kakamega assurance/control officer, the pharmacist room, recruiters room, a staff recreational room; and separate toilets for staff and patients.</p>\n<p>\n <strong>Staffing</strong></p>\n<p>\n MUCRC has a total of 9 Investigators-Prof Abraham Mosigisi Siika, MBChB, MMed, Dr Charles Kwoba, MBChB, MMed, MSc,one Pharmacist-,Natalie Sang, Bpharm one backup associate pharmacist, three backup Pharmacy technologist; one Site Manager; two Study Coordinators;- Viola Cherotich Kirui, BSc,Susan Wanjiru nyambura and Arthur Ogendo ,one Regulatory Affairs Officer;Florence Kiwunja Njulu BSc (EVH)- two QA/QC officer;- two Medical Officers;-Terry Jamatia Tarus, MBChB andHilda Chevera Kaziga, MBChB,six Clinical-Officers -Jairus Kipyego, MPH, BSc, Dip Clinical Medicine & Surgery,Vincent Kipchirchir, Dip Clinical Medicine & Surgery,Viola Samoei, Dip Clinical Medicine & Surgery,Tom Oyoo Osoro, Dip Clinical Medicine & Surgery,Clinton Otieno Achida, Dip Clinical Medicine & Surgery, Getruth Jerop Kiptoo, Dip Clinical Medicine & Surgery,one Data Manager;-Martha Bisieri Mokaya, BSc, MSc,three Assistant Data Managers;-Wilson Lokitala Ekiru, BSc,Ruth Bosire,Cornelius Chege one Phlebotomist; one Laboratory Manager;-Ronald Kibet Tonui, MBChB, MSc. five study nurses-Chris Sande Mboya, Joan Kotut ,Kevin Kipchumba Sang,Eunice Jepkemboi,Philemon Kipchirchir Mutai and eight Recruiters-Cecilia Chebet Mengich,Julie Chepchumba Choge,Amina Msuo Shali,Dorcas Akinyi Opot,Solomon Kimurgor Ngetich,Evans Ochieng Ouno,Shauri Gona and Richard Kipsang Kirui</p>\n
      • other_details_explanation
      • other_details_regulatory_notapproved<p>\n Medicines Control Authority of Zimbabwe-20 Jan 2023</p>\n<p>\n National Drug Authority-Uganda_29 Oct 2022</p>\n<p>\n Medical Research commitee Department of health-United Arab Emirates-24 Nov 2022</p>\n<p>\n MACZ Medicine Control Authority Of Zimbabwe-20th Feb 2023</p>\n<p>\n Tanzania Medicine Device Authority-17 Mar 2023</p>\n
      • other_details_regulatory_approved<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:120px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:120px;\">\n <p>\n Date of approval</p>\n </td>\n <td style=\"width:120px;\">\n <p>\n Number of sites</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:120px;\">\n <p>\n India</p>\n </td>\n <td style=\"width:120px;\">\n <p>\n 27Dec22</p>\n </td>\n <td style=\"width:120px;\">\n <p>\n 34</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:120px;\">\n <p>\n Japan</p>\n </td>\n <td style=\"width:120px;\">\n <p>\n 15Sept22</p>\n </td>\n <td style=\"width:120px;\">\n <p>\n 6</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:120px;\">\n <p>\n Philippines</p>\n </td>\n <td style=\"width:120px;\">\n <p>\n 03Nov22</p>\n </td>\n <td style=\"width:120px;\">\n <p>\n 6</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:120px;\">\n <p>\n Poland</p>\n </td>\n <td style=\"width:120px;\">\n <p>\n 15Dec22</p>\n </td>\n <td style=\"width:120px;\">\n <p>\n 5</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:120px;\">\n <p>\n South Africa</p>\n </td>\n <td style=\"width:120px;\">\n <p>\n 22 Sept22</p>\n </td>\n <td style=\"width:120px;\">\n <p>\n 14</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:120px;\">\n <p>\n US</p>\n </td>\n <td style=\"width:120px;\">\n <p>\n 24Mar22</p>\n </td>\n <td style=\"width:120px;\">\n <p>\n 40</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_rejected
      • other_details_regulatory_halted
      • estimated_duration24 Weeks
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites6
      • multi_country_listNorth America, South America, Europe, Africa, and Asia
      • data_monitoring_committeeYes
      • total_enrolment_per_site15 Participant
      • total_participants_worldwide1490 Participants
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameProf Abraham
      • investigator1_middle_nameMosigisi
      • investigator1_family_nameSiika
      • investigator1_qualificationMaster of Medicine (MMed) in Internal Medicine
      • investigator1_professional_addressCHANDARIA CANCER AND CHRONIC CENTRE AT MOI TEACHING AND REFERRAL HOSPITA
      • investigator1_telephone+254-721280785
      • investigator1_emailabrahamsiika@gmail.com
      • organisations_transferred_Yes
      • number_participantsWe expect that approximately 90 participants, aged between 18 and ≥80 years, will be participating, from 6 sites in Kenya.\n
      • notification<p>\n There are 6 sites participating in the study.Currently 2 sites have received LEC approval-Dr Tina's site-715(Amref) and Prof Abraham Siika-Site 714(IREC).We will send the rest of the approvals letter and other essential documents once available.</p>\n
      • approval_date14-06-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted16-04-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been responded to.
      • final_report
      • implication_results
      • quantity_imported8
      • quantity_dispensed2
      • quantity_destroyed0
      • quantity_exported6
      • balance_site0
      • final_date0000-00-00
      • modified2025-07-07 12:09:02
      • created2023-04-13 12:18:51
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id924
        • application_id1256
        • given_nameProf Abraham
        • middle_nameMosigisi
        • family_nameSiika
        • qualificationMaster of Medicine (MMed) in Internal Medicine
        • professional_addressCHANDARIA CANCER AND CHRONIC CENTRE AT MOI TEACHING AND REFERRAL HOSPITAL
        • telephone+254-721280785
        • emailabrahamsiika@gmail.com
        • created2023-04-13 12:38:47
        • modified2023-04-16 21:14:18
    • SiteDetail(array)
      • 0(array)
        • id1481
        • application_id1256
        • county_id27
        • site_nameMOI UNIVERSITY CLINICAL RESEARCH CENTRE
        • physical_addressCCHANDARIA CANCER AND CHRONIC CENTRE AT MOI TEACHING AND REFERRAL HOSPITAL
        • contact_detailsP.O BOX 4606,3010-ELDORET KENYA
        • contact_personProf Abraham Mosigisi Siika
        • site_capacity(null)
        • misc(null)
        • created2023-04-13 12:38:47
        • modified2023-04-16 21:14:18
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
      • 1(array)
        • id1482
        • application_id1256
        • county_id42
        • site_nameVictoria Biomedical Research Institute,
        • physical_addressVictoria Biomedical Research Institute-Kisumu
        • contact_detailsP.O. Box 7180, Postal Code 40100
        • contact_personDr Lucas Tina
        • site_capacity(null)
        • misc(null)
        • created2023-04-13 15:52:03
        • modified2023-04-16 21:14:18
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1483
        • application_id1256
        • county_id47
        • site_nameKenyatta National Hospital
        • physical_addressKenyatta National Hospital
        • contact_detailsP.O. Box 20723-00202
        • contact_personDr John Kinuthia
        • site_capacity(null)
        • misc(null)
        • created2023-04-13 15:58:16
        • modified2023-04-16 21:14:18
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 3(array)
        • id1484
        • application_id1256
        • county_id37
        • site_nameKEMRI CCR – BUTERE SITE
        • physical_addressBUTERE COUNTY HOSPITAL
        • contact_detailsP.O. Box 40-50101
        • contact_personDr Janet Oyieko
        • site_capacity(null)
        • misc(null)
        • created2023-04-13 16:04:19
        • modified2023-04-16 21:14:18
        • County(array)
          • id37
          • county_nameKakamega
          • created2012-06-15 10:26:29
          • modified2012-06-15 10:26:29
      • 4(array)
        • id1485
        • application_id1256
        • county_id35
        • site_nameKenya Medical Research Institute/Walter Reed Project
        • physical_addressHospital Road, Kericho, Kenya
        • contact_detailsP.O Box 1357 – 20200,
        • contact_personDr. Lucy C. Koech
        • site_capacity(null)
        • misc(null)
        • created2023-04-13 16:07:08
        • modified2023-04-16 21:14:18
        • County(array)
          • id35
          • county_nameKericho
          • created2012-06-15 10:26:16
          • modified2012-06-15 10:26:16
      • 5(array)
        • id1487
        • application_id1256
        • county_id42
        • site_nameKEMRI – AHERO Clinical Trials Units
        • physical_addressAhero County Hospital,
        • contact_detailsP.O. Box 54-40100
        • contact_personDr. Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2023-04-16 16:48:37
        • modified2023-04-16 21:14:18
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id659
        • application_id1256
        • sponsorShionogi*
        • sponsor_typeIndustry
        • contact_personShionogi Pharma Co Ltd Seetsu Plant
        • addressShionogi & Co., Ltd. 1-8, Doshomachi 3-chome, Chuo-ku, Osaka 541-0045 Japan
        • telephone_number+81-6-66382-7341
        • fax_number
        • cell_number+81-6-66382-7341
        • email_addresssimon.portsmouth@shionogi.com
        • created2023-04-13 12:38:47
        • modified2023-04-16 21:14:18
  • 1(array)
    • Application(array)
      • id601
      • user_id611
      • trial_status_id2
      • abstract_of_study<p>\n The clinical presentation of pediatric venous thromboembolic (VTE) disease includes many manifestations, such as catheter-related thrombosis, pulmonary embolism (PE), deep vein thrombosis (DVT), and sinovenous thrombosis. The majority of pediatric subjects (> 95%) with VTE have at least 1 clinical risk factor. Currently, the presence of a central venous catheter is the most important acquired trigger for the development of venous thromboembolic disease in pediatric subjects, contributing to > 90% of all neonatal thrombi and more than half of all thrombi in the older children. Several mechanisms play a role in the development of catheter related thrombosis, including vessel wall injury by the catheter or infused substances (especially parenteral nutrition), compromised blood flow, and thrombogenic effects of the catheter material. Catheter-related thrombi develop in children with long-term venous access devices for diseases such as malignancy, intestinal failure, renal insufficiency, and cystic fibrosis and in children with short-term catheters on the intensive care unit or for cardiac catheterization. Other important risk factors for pediatric thrombosis are congenital heart disease, surgery, immobilization, malignancy, nephrotic syndrome, sepsis, and estrogen treatment. The presence of congenital prothrombotic disorders contribute to the development of pediatric venous thrombosis, as well. Increasing numbers of pediatric subjects with chronic diseases will require anticoagulation as the incidence of VTE events rises due to hypercoagulability and the use of central venous catheters. Currently, the majority of pediatric thrombi are treated with low molecular weight heparin (LMWH) or unfractionated heparin (UFH) followed by LMWH or vitamin K antagonists (VKAs) for a total of 3 to 6 months11. More recently, data exists for the use of fondaparinux in children. Subjects should receive LMWH, UFH, or fondaparinux for at least 5 days following diagnosis of VTE. Guidelines recommend starting VKA on the first treatment day because of slow onset of action. LMWH, UFH, or fondaparinux may be discontinued when the VKA has reached its therapeutic level, as indicated by an international normalized ratio (INR) ≥ 2.0 for 2 or more measurements at least 24 hours apart. Many pediatric subjects have severe underlying diseases which preclude early oral treatment and thus LMWH is continued. In children, the outcome of venous thromboembolic disease has been reported in several studies. The REVIVE trial, a randomized controlled trial comparing LMWH with UFH and VKAs showed a direct mortality rate of 0% in both groups after 3 months. In the Canadian outcome study mortality as result of thrombosis was 2.2%. In the REVIVE trial, recurrent thrombosis occurred in 12.5% of the subjects in the UFH/VKA group and 5.6% in the LMWH group after 3 months of treatment. The recurrence-free survival after 6 months was 93% in pediatric subjects of one center in the Netherlands. Most subjects were treated with LMWH or UFH followed by VKAs. Merkel et al followed 27 subjects treated with LMWH. After a mean time of 2.3 years (range: 0.5 – 6.25 years), 55.6% of the subjects showed complete resolution with radiographic tests, 29.6% partial resolution, and 14.8% no resolution. Newall et al studied radiographic outcome of 22 infants (< 6 months old) and 73 children (≥ 6 months old) after 5 days to 4.2 years. In infants and children, complete resolution occurred in 53% and 47%, partial resolution in 29% and 36%, and no resolution or extension in 18% and 17%, respectively. Post-thrombotic syndrome (PTS) is a manifestation of chronic venous insufficiency following DVT. Children with PTS must endure chronic sequelae for many decades. Goldenberg et al showed that PTS occurrence varied widely (< 10% to 70%) depending on the scoring system; the calculated mean frequency of PTS was 26% (95% confidence interval [CI]: 23% to 28%) among a total of nearly 1000 subjects with upper extremity (UE)/lower extremity (LE) DVT. In the cross-sectional study, multiple logistic regression analysis revealed that lack of thrombus resolution was associated with a statistically significant 4 fold increase in odds of PTS. Therefore we propose to evaluate edoxaban on the reduction of thrombotic burden defined by “no change and extension” of the thrombus at the month 3 visit. Edoxaban is an oral direct inhibitor of activated Factor X with predictable pharmacokinetics (PK) and pharmacodynamics (PD). As a result, anticoagulant effects are more likely to remain within the therapeutic range, thereby decreasing the likelihood of bleeding, and potentially removing the need for dose adjustment or frequent monitoring. These advantages may result in increased patient satisfaction and adherence compared with existing anticoagulants Edoxaban has been approved for the following indications in the US: • To reduce the risk of stroke and systemic embolism (SE) in subjects with nonvalvular atrial fibrillation (NVAF) with limitation of use in patients with CrCL > 95 mL/min. • Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5 to 10 days of initial therapy with a parenteral anticoagulant. In the EU and Japan, edoxaban has been approved for the following indications: • Prevention of stroke and systemic embolism in adult subjects with nonvalvular atrial fibrillation (NVAF) with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack (TIA) with no limitation of use. • Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults . This study will evaluate the benefits and risks of edoxaban in pediatric subjects with thromboembolic disease.</p>\n
      • study_title<p>\n A PHASE 3, OPEN-LABEL, RANDOMIZED, MULTICENTER, CONTROLLED TRIAL TO EVALUATE THE PHARMACOKINETICS AND PHARMACODYNAMICS OF EDOXABAN AND TO COMPARE THE EFFICACY AND SAFETY OF EDOXABAN WITH STANDARD OF CARE ANTICOAGULANT THERAPY IN PEDIATRIC SUBJECTS FROM BIRTH TO LESS THAN 18 YEARS OF AGE WITH CONFIRMED VENOUS THROMBOEMBOLISM (VTE)</p>\n
      • laymans_summary<p>\n The clinical presentation of pediatric venous thromboembolic (VTE) disease includes many manifestations, such as catheter-related thrombosis, pulmonary embolism (PE), deep vein thrombosis (DVT), and sinovenous thrombosis. The majority of pediatric subjects (>95%) with VTE have at least 1 clinical risk factor. Currently, the presence of a central venous catheter is the most important acquired trigger for the development of venous thromboembolic disease in pediatric subjects, contributing to >90% of all neonatal thrombi and more than half of all thrombi in the older children1, 2 3, 4. Several mechanisms play a role in the development of catheter related thrombosis, including vessel wall injury by the catheter or infused substances (especially parenteral nutrition), compromised blood flow, and thrombogenic effects of the catheter material5. Catheter-related thrombi develop in children with long-term venous access devices for diseases such as malignancy, intestinal failure, renal insufficiency, and cystic fibrosis and in children with short-term catheters on the intensive care unit or for cardiac catheterization6, 7, 8. Other important risk factors for pediatric thrombosis are congenital heart disease, surgery, immobilization, malignancy, nephrotic syndrome, sepsis, and estrogen treatment. The presence of congenital prothrombotic disorders contribute to the development of pediatric venous thrombosis, as well9. Increasing numbers of pediatric subjects with chronic diseases will require anticoagulation as the incidence of VTE events rises due to hypercoagulability and the use of central venous catheters1</p>\n<p>\n <br />\n  </p>\n
      • short_titleThe Edoxaban Hokusai VTE PEDIATRICS Study
      • protocol_noECCT/17/03/02
      • version_noVERSION 1.0
      • date_of_protocol16-04-2016
      • study_drugEdoxaban (DU-176b)
      • disease_conditionTreatment and secondary prevention of VTE
      • product_type_biologicals1
      • product_type_proteins1
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameStandard of care (SOC; including low Molecular weight heparin (LMWH), vitamin K antagonist (VKA), or synthetic pentasaccharide (SP) Xa inhibitors)
      • comparator_registeredyes
      • comparator_countriesworldwide
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressMshitindo@strathmore.edu
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries1
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantAmina Salim
      • declaration_date116-03-2017
      • declaration_principal_investigatorBernhards Ogutu Ragama
      • declaration_date216-03-2017
      • placebo_presentNo
      • study_objectives<p>\n The primary objective is to demonstrate the non-inferiority of edoxaban to standard of care (SOC; including low molecular weight heparin (LMWH), vitamin K antagonist (VKA), or synthetic pentasaccharide (SP) Xa inhibitors) in the treatment and secondary prevention of VTE in pediatric subjects with regard to the composite efficacy endpoint (ie, symptomatic recurrent VTE, death as result of VTE, and no change or extension of thrombotic burden) during the first 3-month treatment period.</p>\n
      • principal_inclusion_criteria<p>\n <strong>Subject Eligibility Criteria: Inclusion Criteria: </strong></p>\n<p>\n Subjects must satisfy all of the following criteria to be included in the study:</p>\n<p style=\"margin-left:.25in;\">\n 1.� � � Male or female pediatric subjects between birth (defined as 38 weeks gestational age) and less than</p>\n<p style=\"margin-left:.25in;\">\n 18 years of age at the time of consent.</p>\n<p style=\"margin-left:.25in;\">\n 2.� � � Pediatric subjects with the presence of documented VTE confirmed by appropriate diagnostic imaging and requiring anticoagulant therapy for at least 90 days (list of VTE provided in Section 7.1).</p>\n<p style=\"margin-left:.25in;\">\n 3.� � � Subjects must have received at least 5 days of heparin (LMWH or SP Xa inhibitors or UFH according to the edoxaban label for VTE treatment) therapy prior to randomization to treat the newly identified index VTE. In addition, prior to being randomized to edoxaban or SOC, subjects initially treated with VKA are recommended to have an INR < 2.0.</p>\n<p style=\"margin-left:.25in;\">\n 4.� � � Subject and/or parent(s)/legal guardian(s) or legally acceptable representative is informed and provides signed consent for the child to participate in the study with edoxaban treatment. Pediatric subjects with appropriate intellectual maturity will be required to sign an assent form in addition to the signed informed consent from the parent(s)/legal guardian(s) or any legally acceptable representative.</p>\n<p style=\"margin-left:.25in;\">\n 5.� � � Female subjects who have menarche must test negative for pregnancy at Screening and must consent to avoid becoming pregnant by using an approved contraception method throughout the study.</p>\n
      • principal_exclusion_criteria<p>\n <strong>Exclusion Criteria:</strong></p>\n<p>\n Subjects who meet any of the following criteria will be disqualified from entering the study:</p>\n<p style=\"margin-left:.25in;\">\n 1.� � � Subjects with active bleeding or high risk of bleeding contraindicating treatment with LMWH, SP Xa inhibitors, VKAs, or direct oral anticoagulants (DOACs; identified high risk of bleeding during prior experimental administration of DOACs).</p>\n<p style=\"margin-left:.25in;\">\n 2.� � � Subjects who have been or are being treated with thrombolytic agents, thrombectomy or insertion of a caval filter for the newly identified index VTE.</p>\n<p style=\"margin-left:.25in;\">\n 3.� � � Administration of antiplatelet therapy is contraindicated in both arms except for low dose aspirin defined as 1-5 mg/Kg/day with maximum of 100 mg/day (see Appendix 17.3.1).</p>\n<p style=\"margin-left:.25in;\">\n 4.� � � Subjects with hepatic disease associated with coagulopathy leading to a clinically relevant bleeding risk (aPTT > 50 seconds or international normalized ratio [INR] > 2.0 not related to anticoagulation therapy) or ALT > 5 × the upper limit of normal (ULN) or total bilirubin > 2 × ULN with direct bilirubin > 20% of the total at Screening Visit.</p>\n<p style=\"margin-left:.25in;\">\n 5.� � � Subjects with glomerular filtration rate (GFR) < 30% of normal for age and size (see Appendix 17.6) as determined by the Schwartz formula.</p>\n<p style=\"margin-left:.25in;\">\n 6.� � � Subjects with stage 2 hypertension defined as blood pressure (BP) systolic and/or diastolic confirmed > 99th percentile + 5 mmHg (see Appendix 17.7).</p>\n<p style=\"margin-left:.25in;\">\n 7.� � � Subject with thrombocytopenia < 50 × 109/L at Screening Visit. Subjects with a history of heparin induced thrombocytopenia may be enrolled in the study at the Investigator’s discretion.</p>\n<p style=\"margin-left:.25in;\">\n 8.� � � Life expectancy less than the expected study treatment duration (3 months).</p>\n<p style=\"margin-left:.25in;\">\n 9.� � � Subjects who are known to be pregnant or breastfeeding.</p>\n<p style=\"margin-left:.25in;\">\n 10. Subjects with any condition that, as judged by the Investigator, would place the subject at increased risk of harm if he/she participated in the study.</p>\n
      • primary_end_points<p>\n <strong>Study Endpoints: </strong></p>\n<p>\n All safety and efficacy endpoints described below will be adjudicated in a blinded manner by the Clinical Events Committee (CEC).</p>\n<p>\n <strong>Primary Efficacy Endpoint:</strong></p>\n<p>\n The primary efficacy endpoint is a composite endpoint consisting of the incidence of symptomatic recurrent venous thromboembolic disease, death as a result of VTE, and no change or extension of thrombotic burden (Section 7.1) during the first 3 months period.</p>\n<p>\n <strong>Secondary Efficacy Endpoints:</strong></p>\n<p>\n The secondary efficacy endpoints include:</p>\n<p style=\"margin-left:.25in;\">\n ·ï¿½ � � � � � � � A composite endpoint consisting of symptomatic recurrent venous thromboembolic disease, death as a result of VTE, and no change or extension of thrombotic burden from randomization to the date of the last dose of study drug + 30 days .</p>\n<p style=\"margin-left:.25in;\">\n ·ï¿½ � � � � � � � The individual components of the primary efficacy endpoint during the first 3-month period:</p>\n<p style=\"margin-left:.75in;\">\n o� � Symptomatic recurrent VTE</p>\n<p style=\"margin-left:.75in;\">\n o� � Death as a result of VTE</p>\n<p style=\"margin-left:.75in;\">\n o� � No change or extension of thrombotic burden</p>\n<p style=\"margin-left:.25in;\">\n ·ï¿½ � � � � � � � All-cause mortality from randomization to last dose + 30 days.</p>\n<p style=\"margin-left:.25in;\">\n ·ï¿½ � � � � � � � The DVT, Catheter-related thrombosis, PE, sinovenous thrombosis events within and after the first 3-month treatment period.</p>\n<p>\n <strong>Net Clinical Outcome Endpoint:</strong></p>\n<p>\n Composite of symptomatic recurrent VTE events, death as a result of VTE, and major and CRNM bleeding that occurred from the date of the first dose of study drug to the date of last dose of study drug + 30 days.</p>\n<p>\n <strong>Safety Endpoints:</strong></p>\n<p>\n The safety endpoints are:</p>\n<p style=\"margin-left:.25in;\">\n ·ï¿½ � � � � � � � A combination of major and clinically relevant non- major (CRNM) bleedings occurring during treatment or within 3 days of completing or interrupting or stopping study during the first 3- month treatment period.</p>\n<p style=\"margin-left:.25in;\">\n ·ï¿½ � � � � � � � All bleedings from first to the last dose + 30 days.</p>\n<p style=\"margin-left:.25in;\">\n ·ï¿½ � � � � � � � A combination of major and CRNM bleedings from first to the last dose + 30 days.</p>\n<p>\n <strong>Pharmacokinetic and Pharmacodynamic Endpoints:</strong></p>\n<p>\n Will apply only in the 60 subjects in front-end multiple dose assessment</p>\n<p>\n <strong>Pharmacokinetics:</strong></p>\n<p>\n Using population PK analysis, the following PK parameters will be estimated: apparent systemic clearance (CL/F) and apparent volume of distribution (V/F) of edoxaban.</p>\n<p>\n <strong>Pharmacodynamics:</strong></p>\n<p>\n The following biomarkers of coagulation will be estimated: PT, aPTT, anti-FXa for edoxaban treatment arm</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic1
      • scope_pharmacogenomic1
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:648px;\" width=\"648\">\n <tbody>\n <tr>\n <td style=\"width:102px;\">\n <p align=\"center\">\n <strong>No of staff</strong></p>\n </td>\n <td style=\"width:144px;\">\n <p align=\"center\">\n <strong>Name</strong></p>\n </td>\n <td style=\"width:276px;\">\n <p align=\"center\">\n <strong>Qualifications</strong></p>\n </td>\n <td style=\"width:126px;\">\n <p align=\"center\">\n <strong>Experience</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:102px;\">\n <p align=\"center\">\n 1</p>\n </td>\n <td style=\"width:144px;\">\n <p>\n Bernhards Ogutu</p>\n </td>\n <td style=\"width:276px;\">\n <p>\n PhD (Clinical Pharmacology), (MMed) (Paediatrics), MBChB</p>\n <p>\n �</p>\n </td>\n <td style=\"width:126px;\">\n <p>\n Principal Investigator</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:102px;\">\n <p align=\"center\">\n 1</p>\n </td>\n <td style=\"width:144px;\">\n <p>\n Jessie Githanga</p>\n </td>\n <td style=\"width:276px;\">\n <p>\n MBChB, MMed (Path)(UON), FCPath ECSA</p>\n </td>\n <td style=\"width:126px;\">\n <p>\n Co- Principal Investigator</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:102px;\">\n <p align=\"center\">\n 1</p>\n </td>\n <td style=\"width:144px;\">\n <p>\n Anastacia Omoding</p>\n </td>\n <td style=\"width:276px;\">\n <p>\n � (MMed) (Paediatrics), MBChB, C.P.A 1 & 2</p>\n </td>\n <td style=\"width:126px;\">\n <p>\n Associate investigator</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:102px;\">\n <p align=\"center\">\n 1</p>\n </td>\n <td style=\"width:144px;\">\n <p>\n Christine Jowi</p>\n </td>\n <td style=\"width:276px;\">\n <p>\n MB ChB M.Med (Paed)</p>\n </td>\n <td style=\"width:126px;\">\n <p>\n Cardiologist</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:102px;\">\n <p align=\"center\">\n 1</p>\n </td>\n <td style=\"width:144px;\">\n <p>\n Amina Salim</p>\n </td>\n <td style=\"width:276px;\">\n <p>\n Msc Clinical Trials, Dip. Clinical Medicine & Surgery</p>\n </td>\n <td style=\"width:126px;\">\n <p>\n Study coordinator</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:648px;\">\n <p align=\"center\">\n <strong>SITE FACILITIES</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:102px;height:64px;\">\n <p>\n 2 level five hospitals</p>\n </td>\n <td style=\"width:144px;height:64px;\">\n <p style=\"margin-left:.25in;\">\n 1.� � � � Mater Hospital</p>\n <p style=\"margin-left:.25in;\">\n 2.� � � � Gertrudes Hospital</p>\n </td>\n <td colspan=\"2\" style=\"width:402px;height:64px;\">\n <p>\n Dental facility,� � � Minor OT,� � � Physiotherapy, Laboratory services,� � � ECG Services, Pharmacy, X-Ray services, Ambulance Services, HDU,ICU, in patient services, outpatient services, Staff capacity, ward facilities</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n �</p>\n
      • other_details_explanation<p>\n This study is being conducted worldwide in different regions.</p>\n
      • other_details_regulatory_notapproved<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:639px;\" width=\"639\">\n <thead>\n <tr>\n <th style=\"width:272px;height:47px;\">\n <p align=\"center\">\n <strong><u>Country</u></strong></p>\n </th>\n <th style=\"width:163px;height:47px;\">\n <p align=\"center\">\n <strong><u>Submission Status</u></strong></p>\n </th>\n <th style=\"width:205px;height:47px;\">\n <p align=\"center\">\n <strong><u>Regulatory Authority Decision and Date</u></strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Brazil</p>\n <p>\n <strong><u>ANVISA - Agência Nacional de Vigilância Sanitária</u></strong></p>\n <p>\n SIA, Trecho 5, Área Especial 57, Bloco B, Térreo<br />\n Brasília -DF - CEP: 71205-050� - Brasil</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 21 Dec 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p>\n �</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Croatia</p>\n <p>\n <strong><u>Ministry of Health</u></strong></p>\n <p>\n Ksaver 200a</p>\n <p>\n 10 000 Zagreb</p>\n <p>\n �</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 23 Dec 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p>\n �</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Denmark</p>\n <p>\n <strong><u>Danish Data Protection Agency</u></strong></p>\n <p>\n <strong><u>Datatilsynet</u></strong><br />\n Borgergade 28, 5.<br />\n DK-1300 Copenhagen K.</p>\n <p>\n �</p>\n <p>\n <strong><u>Danish Health Authority</u></strong></p>\n <p>\n Islands Brygge 67<br />\n 2300 Copenhagen S</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 22 Dec 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p>\n �</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Egypt</p>\n <p>\n <strong><u>Egyptian Ministry of Health-Central Administration for Research and Health Development (CCRHD)</u></strong></p>\n <p>\n 3 Magles El Shaab Street, Garden City,Cairo</p>\n <p>\n �</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 20 Sep 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p>\n �</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Germany</p>\n <p>\n <strong><u>Bundesinstitut für Arzneimittel und Medizinprodukte</u></strong><br />\n Kurt-Georg-Kiesinger-Allee 3<br />\n 53175 Bonn</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 13 Sep 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p>\n �</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Malaysia</p>\n <p>\n <strong><u>National Pharmaceutical Control Bureau</u></strong></p>\n <p>\n Lot 36, Jalan Universiti</p>\n <p>\n 46200 Petaling Jaya,</p>\n <p>\n Selangor, Malaysia</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 13 Jan 2017</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p>\n �</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Romania</p>\n <p>\n <strong><u>Ministerul Sanatatii</u></strong></p>\n <p>\n Agentia Nationala a Medicamentului si a Dispozitivelor Medicale</p>\n <p>\n Str. Aviator Sanatescu 48, Sector 1, 011478, Bucuresti</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 21 Sep 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p>\n �</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Serbia</p>\n <p>\n <strong><u>Medicines and Medical Devices Agency of Serbia </u></strong></p>\n <p>\n Vojvode Stepe 458, 11</p>\n <p>\n 152 Belgrade</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 8 Dec 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p>\n �</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Slovenia</p>\n <p>\n <strong><u>Public Agency of the Republic of Slovenia for Medicinal Products and Medical Devices </u></strong></p>\n <p>\n Slovenčeva ulica 22</p>\n <p>\n SI-1000 Ljubljana</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 31 Oct 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p>\n �</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Ukraine</p>\n <p>\n <strong><u>Ministry of Health of Ukraine</u></strong></p>\n <p>\n 7 Hrushevskoho str.</p>\n <p>\n Kyiv, 01601</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 20 Oct 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p>\n �</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n �</p>\n
      • other_details_regulatory_approved<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:639px;\" width=\"639\">\n <thead>\n <tr>\n <th style=\"width:272px;height:47px;\">\n <p align=\"center\">\n <strong><u>Country</u></strong></p>\n </th>\n <th style=\"width:163px;height:47px;\">\n <p align=\"center\">\n <strong><u>Submission Status</u></strong></p>\n </th>\n <th style=\"width:205px;height:47px;\">\n <p align=\"center\">\n <strong><u>Regulatory Authority Decision and Date</u></strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Canada</p>\n <p>\n <strong><u>Health Canada</u></strong><br />\n Address Locator 0900C2<br />\n Ottawa, Ontario<br />\n K1A 0K9</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 9 Sep 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p>\n Approved – 12 Oct 2016</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Czech Republic</p>\n <p>\n <strong><u>Státní ústav pro kontrolu léčiv</u></strong></p>\n <p>\n � robárova 48</p>\n <p>\n 100 41 Praha 10</p>\n <p>\n Czech Republic</p>\n <p>\n �</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 14 Jul 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p align=\"center\">\n Approved 15 Nov 2016</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n France</p>\n <p>\n <strong><u>ANSM: Agence Nationale de Sécurité du Médicament et des produits de santé</u></strong><br />\n 143/147, boulevard Anatole France<br />\n 93285 SAINT-DENIS CEDEX</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 30 Aug 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p align=\"center\">\n Approved 28 Oct 2016</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Hungary</p>\n <p>\n <strong><u>Országos Gyógyszerészeti és Élelmezés-egészségügyi Intézet (OGYÉI)/ National Institute of Pharmacy and Nutrition</u></strong></p>\n <p>\n 1051 Budapest, Zrínyi utca 3.</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 15-Aug-16</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p align=\"center\">\n Approved 25 Oct 2016</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Israel</p>\n <p>\n <strong><u>Ministry of Health</u></strong></p>\n <p>\n 39 Yermiyahu st, Jerusalem</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 30-Jun-16</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p align=\"center\">\n Approved 20 Dec 2016</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Korea, Republic of</p>\n <p>\n <strong><u>Ministry of Food and Drug Safety (MFDS)</u></strong></p>\n <p>\n 187 Osongsaengmyeong-2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, 28159, South Korea</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 29 Jun 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p align=\"center\">\n Approved 11 Oct 2016</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Netherlands</p>\n <p>\n <strong><u>Central Committee on Research Involving Human Subjects (CCMO)</u></strong></p>\n <p>\n Parnassusplein 5</p>\n <p>\n 2511 VX The Hague</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 21 Dec 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p align=\"center\">\n Approved 6 Jan 2017</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Portugal</p>\n <p>\n <strong><u>INFARMED - Autoridade Nacional do Medicamento e Produtos de Saúde, IP</u></strong></p>\n <p>\n Parque de Saúde de Lisboa - Avenida do Brasil, 53<br />\n 1749-004 Lisboa</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 29 Jul 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p align=\"center\">\n Approved 19 Dec 2016</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Russia</p>\n <p>\n <strong><u>Ethical Council</u></strong></p>\n <p>\n <strong><u>Ministry of Health of Russian Federation</u></strong></p>\n <p>\n 127 994, Moscow, Rakhmanovsky lane, 3</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 29 Jul 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p align=\"center\">\n Approved 30 Nov 2016</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Singapore</p>\n <p>\n <strong><u>Health Sciences Authority</u></strong></p>\n <p>\n 11 Biopolis Way</p>\n <p>\n #11-01, Helios</p>\n <p>\n Singapore 138667</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 6 Aug 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p align=\"center\">\n Approved 21 Sep 2016</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Spain</p>\n <p>\n <strong><u>Ag</u></strong><a href=\"http://www.aemps.gob.es/\"><strong>encia Española de Medicamentos y Productos Sanitarios</strong></a><br />\n Parque Empresarial Las Mercedes</p>\n <p>\n Edificio 8, Calle Campezo 1</p>\n <p>\n 28022 Madrid</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 13 Sep 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p align=\"center\">\n Approved 27 Oct 2016</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Turkey</p>\n <p>\n <strong><u>Turkish Medicine and Medical Device Agency</u></strong></p>\n <p>\n Sogutozu Mahallesi 2176 Sokak No:5 �</p>\n <p>\n 06520 Cankaya Ankara</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 28 Sep 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p align=\"center\">\n Approved 11 Jan 2017</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n United States</p>\n <p>\n <strong><u>Food and Drug Administration</u></strong><br />\n 10903 New Hampshire Ave<br />\n Silver Spring, MD 20993-0002</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 15 Aug 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p align=\"center\">\n Tacit approval – 15 Sep 2016</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n �</p>\n
      • other_details_regulatory_rejected<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:639px;\" width=\"639\">\n <thead>\n <tr>\n <th style=\"width:272px;height:47px;\">\n <p align=\"center\">\n <strong><u>Country</u></strong></p>\n </th>\n <th style=\"width:163px;height:47px;\">\n <p align=\"center\">\n <strong><u>Submission Status</u></strong></p>\n </th>\n <th style=\"width:205px;height:47px;\">\n <p align=\"center\">\n <strong><u>Regulatory Authority Decision and Date</u></strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td style=\"width:272px;height:50px;\">\n <p>\n Italy</p>\n <p>\n <strong><u>AIFA</u></strong></p>\n <p>\n Ufficio Ricerca e Sperimentazione Clinica</p>\n <p>\n Via del Tritone, 181</p>\n <p>\n 00187 Rome</p>\n </td>\n <td style=\"width:163px;height:50px;\">\n <p align=\"center\">\n Submitted 22 Sep 2016</p>\n </td>\n <td style=\"width:205px;height:50px;\">\n <p align=\"center\">\n Denied 9 Dec 2016</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n �</p>\n
      • other_details_regulatory_halted
      • estimated_duration4.5 years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorStandard of care (SOC; in
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherYes
      • design_controlled_medicinal_specifyStandard of care (SOC; including low Molecular weight heparin (LMWH), vitamin K antagonist (VKA), or synthetic pentasaccharide (SP) Xa inhibitors)
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states32
      • number_of_sites2
      • multi_country_listArgentina, Brazil, Bulgaria, Canada, Chile, Croatia, Czech Republic, Denmark, Egypt, France, Germany, Hungary, India, Israel, Italy, Kenya, South Korea, Lebanon, Malaysia, Mexico, Netherlands, Portugal, Romania, Russia, Serbia, Singapore, Slovenia, Spain, Thailand, Turkey, Ukraine, United States
      • data_monitoring_committeeYes
      • total_enrolment_per_siteN/A
      • total_participants_worldwide274
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornYes
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentYes
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBernhards Ogutu
      • investigator1_middle_name
      • investigator1_family_nameRagama
      • investigator1_qualificationPhD (Clinical Pharmacology), MMed (Paediatrics), MBChB
      • investigator1_professional_addressCentre for Research in Therapeutic Sciences, Strathmore University, P.O Box 59857-0020
      • investigator1_telephone+254733812613
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_Yes
      • number_participants10
      • notification<p>\n please find attached ;</p>\n<p>\n  </p>\n<ul>\n <li>\n Independent Data Monitoring Committee Report for Data Review meeting # 10</li>\n <li>\n cover letter dated 6th march 2020</li>\n</ul>\n
      • approval_date03-10-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted04-05-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2021-03-25 10:00:02
      • created2017-03-16 12:34:46
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id381
        • application_id601
        • given_nameBernhards Ragama
        • middle_nameOgutu
        • family_nameRagama
        • qualificationPhD (Clinical Pharmacology), (MMed) (Paediatrics), MBChB
        • professional_addressCentre for Research in Therapeutic Sciences, Strathmore University (CREATES,SU), P.O BOX 59857-00200, Nairobi
        • telephone+254 733 812613
        • emailogutu6@gmail.com
        • created2017-03-16 12:49:04
        • modified2020-05-04 12:03:13
    • SiteDetail(array)
      • 0(array)
        • id480
        • application_id601
        • county_id47
        • site_nameGertrudes Hospital
        • physical_address Muthaiga Rd, Nairobi, Kenya
        • contact_detailsP. O. Box 42325 Muthaiga Rd, Nairobi, Kenya
        • contact_personTruphena Otinyo
        • site_capacity(null)
        • misc(null)
        • created2017-03-16 12:49:04
        • modified2020-05-04 12:03:13
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id481
        • application_id601
        • county_id47
        • site_nameMater Hospital
        • physical_addressalong Dunga Road, South B, Nairobi.
        • contact_detailsalong Dunga Road, South B, Nairobi. Telephone: +254 (20) 690 3000
        • contact_personMedical Director
        • site_capacity(null)
        • misc(null)
        • created2017-03-17 11:13:04
        • modified2020-05-04 12:03:13
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id305
        • application_id601
        • sponsorDaiichi Sankyo, Inc. 399 Thornall Street Edison, NJ 08837
        • sponsor_typeIndustry
        • contact_personRika Pieterse
        • addressMontrose Place 2 Bella Rosa Street Rosenpark, Bellville Cape Town, South Africa 7530
        • telephone_numberOffice: +27 21 9175823
        • fax_number
        • cell_numberMobile: +27 83 6520915
        • email_addressrika.pieterse@iqvia.com
        • created2017-03-16 12:49:04
        • modified2020-05-04 12:03:13
  • 2(array)
    • Application(array)
      • id674
      • user_id954
      • trial_status_id4
      • abstract_of_study<div>\n <u><strong>Investigational Product: </strong></u></div>\n<div>\n Voxelotor as 300 and 500 mg tablets or as 300, 400, 600, and 900 mg powder for oral suspension (packaged in stick pack pouches) Matching placebo</div>\n<div>\n  </div>\n<div>\n <u><strong>Number of Clinical Sites</strong></u>:  The study will be conducted at approximately 50 international clinical sites.</div>\n<div>\n <u><strong>Number of Study Participants</strong></u>:  Approximately 224 participants with sickle cell disease (SCD), aged ≥ 2 to < 15 years.</div>\n<div>\n  </div>\n<div>\n <u><strong>Treatment:</strong></u>  Participants will be randomized in a 1:1 ratio to receive voxelotor or placebo. All participants younger than 12 years of age and randomized to voxelotor will receive a dose based on their body weight, to provide exposure corresponding to the adult dose of 1500 mg/day. Participants 12 years or older will take 1500 mg/day.<br />\n Participants will receive study drug as a tablet formulation or powder for oral suspension formulation (packaged in stick pack pouches).<br />\n The tablet formulation is to be administered orally, once daily. Once swallowed, the tablet should be followed by drinking a liquid such as water. The powder for oral<br />\n suspension formulation is to be dispersed in liquid and administered orally, once daily. Both dosage forms may be taken with or without food.<br />\n The participant’s weight at screening will be used to determine their initial treatment dose. Dosing should be adjusted if the participant’s weight increases or decreases over 2 consecutive clinic visits. Participant’s weight will be measured and dose adjustments made as needed, as outlined in the protocol.</div>\n<div>\n  </div>\n<div>\n <u><strong>Objectives:</strong></u></div>\n<div>\n <u><strong>Primary Objective:</strong></u><br />\n The primary objective is to evaluate the effect of voxelotor compared to placebo on the transcranial Doppler (TCD) time-averaged mean of the maximum velocity<br />\n (TAMMV) arterial cerebral blood flow at 24 weeks in SCD participants ≥ 2 to < 15 years of age with conditional (170 to < 200 cm/sec) TCD flow velocity.<br />\n <u><strong>Secondary Objectives</strong></u>:<br />\n The secondary objectives are to evaluate the effects of voxelotor compared to placebo on:</div>\n<ul>\n <li>\n ï‚·Change in TCD flow velocity at Week 48 and Week 96 ï‚·</li>\n <li>\n     Conversion of TCD category from conditional to abnormal</li>\n <li>\n ï‚· Reversion of TCD category from conditional to normal</li>\n <li>\n     Change in hemoglobin (Hb) over time</li>\n <li>\n     Change in clinical measures of hemolysis</li>\n</ul>\n<div>\n <u><strong>Exploratory Objectives:</strong></u><br />\n The exploratory objectives will assess the effect of voxelotor compared to placebo on:</div>\n<ul>\n <li>\n ï‚·        Growth (height, weight, and head circumference)</li>\n <li>\n ï‚·        Neuro-cognitive function</li>\n <li>\n ï‚·        Patient reported symptoms and quality of life</li>\n <li>\n ï‚·        Physician assessed change in global health status</li>\n <li>\n ï‚·        Healthcare utilization</li>\n <li>\n ï‚·        Exploratory biomarkers</li>\n</ul>\n<div>\n <u><strong>Safety Objectives:</strong></u><br />\n The safety objective is to assess the safety and tolerability of voxelotor compared to placebo.<br />\n <u><strong>Pharmacokinetic Objectives</strong></u>:<br />\n The pharmacokinetic (PK) objective is to assess the PK of voxelotor as evaluated by population pharmacokinetics (PPK) analysis.</div>\n<p>\n <u><strong>Study Design:</strong></u></p>\n<p>\n The study will be conducted globally at approximately 50 clinical sites.</p>\n<div>\n The study consists of 3 periods:<br />\n ï‚·        Screening: up to 35 days prior to randomization<br />\n ï‚·        Treatment: 96 weeks<br />\n ï‚·        Follow-Up: 28 days (4 weeks) after the last dose<br />\n Approximately 224 participants aged 2 to < 15 years will be randomized 1:1 to voxelotor or placebo.<br />\n Participants ≥ 12 years old will be administered a fixed dose of voxelotor 1500 mg/day. Participants younger than 12 years of age will receive voxelotor at a weight-based (1500 mg-equivalent) dose.<br />\n Following completion of study treatment, eligible participants will be given the option to enroll in an open-label extension study (under a separate protocol) to receive voxelotor for a minimum of 3 years (3 years or until commercial product becomes available, whichever is longer).<br />\n At the time of randomization, participants will be stratified by hydroxyurea (HU) use (yes/no), age (2 to ≤ 8 years; > 8 to < 15 years), Screening TCD flow velocity value (170 to < 185 cm/sec; 185 to < 200 cm/sec) and geographic region (Africa including Middle East and North Africa [MENA]; rest of world). Stratification of participants by age was chosen to evenly balance by age distribution using the expected median age of 8 years.</div>\n<div>\n Dosing of participants between 2 and < 4 years of age:</div>\n<div>\n At least 15 participants from 2 to < 4 years of age will be enrolled. Enrollment of participants <4 years of age will be initiated after the Data and Safety Monitoring Board (DSMB) has reviewed safety and PK data from at least 12 participants < 30 kg treated with voxelotor for at least 28 days. These data for at least 12 participants may be generated from any voxelotor clinical studies.</div>\n<div>\n  </div>\n<div>\n <u><strong>Duration of Study Participation:</strong></u>  The duration of study involvement for an individual participant is expected to be approximately 105 weeks.<br />\n The study will end when the last participant’s last visit occurs.</div>\n<div>\n  </div>\n<div>\n <u><strong>Statistical Methods:</strong></u></div>\n<div>\n <u>Primary Endpoint</u><br />\n The primary efficacy endpoint is the change from Baseline at 24 weeks in TAMMV arterial cerebral blood flow, as measured by TCD. Secondary Endpoints<br />\n The secondary efficacy endpoints are as follows:</div>\n<ul>\n <li>\n Change from Baseline in TCD flow velocity at Week 48 and Week 96 ï‚·       </li>\n <li>\n Incidence of conversion to abnormal TCD flow velocity (≥ 200 cm/sec) over 24, 48, and 96 weeks</li>\n <li>\n Incidence of reversion to normal TCD flow velocity (<170 cm/sec) over 24, 48, and 96 weeks</li>\n <li>\n Proportion of participants with TCD flow velocity reduction ≥ 15 cm/sec at Week 24, Week 48, and Week 96</li>\n <li>\n Change in Hb from Baseline at Week 24, Week 48, and Week 96</li>\n <li>\n Change in clinical measures of hemolysis (unconjugated bilirubin, % reticulocyte, absolute reticulocyte, and lactate dehydrogenase [LDH]) from Baseline at Week 24, Week 48, and Week 96</li>\n</ul>\n<div>\n <u>Exploratory Endpoints:</u><br />\n The exploratory endpoints are as follows:</div>\n<ul>\n <li>\n ï‚·        Growth and development as assessed by change from Baseline in height, weight, and head circumference</li>\n <li>\n ï‚·        Neurocognitive function assessed by National Institutes of Health (NIH) toolbox for processing speed</li>\n <li>\n ï‚·        Participant fatigue assessed by the Peds QL Multidimensional Fatigue Scale</li>\n <li>\n ï‚·        Number of missed school days (if applicable) due to SCD</li>\n <li>\n ï‚·        Number of missed work days (if applicable) of the primary caregiver due to participant’s SCD</li>\n <li>\n ï‚·        Investigator assessment of change in the overall health condition of the participant assessed with Clinical Global Impression– Change (CGI-C)</li>\n <li>\n ï‚·        Exploratory biomarkers (dense cells, creatinine:albumin ratio assessments)</li>\n <li>\n ï‚·        Healthcare resource utilization (eg, incidence of hospitalizations, emergency room/clinic visits)</li>\n</ul>\n<div>\n <u>Safety Endpoints</u><br />\n The safety endpoints include adverse events (AEs), clinical laboratory assessments, and vital signs.<br />\n <u>Pharmacokinetic Endpoint</u><br />\n The endpoint is whole blood and plasma voxelotor PK as evaluated by PPK analysis using nonlinear mixed effects modeling.</div>\n<div>\n  </div>\n<div>\n <u><strong>Sample Size</strong></u><br />\n The sample size is planned to provide sufficient statistical power for the primary efficacy analysis and for a robust safety database. In addition, the number of events required to assess secondary efficacy endpoints, eg, percentage conversion to abnormal TCD category, is also considered.</div>\n<div>\n <br />\n For the primary endpoint (change from Baseline in TCD flow velocity [cm/sec]), assuming equal allocation across treatment groups and a common variance, an estimate of the number of participants in each of 2 treatment groups used the following assumptions in the power calculation:</div>\n<ul>\n <li>\n ï‚·    Targeted treatment effect: difference in mean change from Baseline in TCD flow velocity is 15 cm/sec</li>\n <li>\n ï‚·    Common standard deviation is 24 cm/sec</li>\n <li>\n ï‚·    A significance level of 5% (2-sided)</li>\n</ul>\n<div>\n Assuming a 20% drop out rate, a sample size of 112 participants per group provides > 95% power to detect the targeted treatment effect for the following hypothesis test using a Student’s t-test:</div>\n<div>\n  </div>\n<div>\n H₀:µ₁=µ₂   vs.  <span style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 12px; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; word-spacing: 0px; float: none; display: inline !important; white-space: normal; orphans: 2; background-color: rgb(255, 255, 255); -webkit-text-stroke-width: 0px;\">H_A:<span style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 12px; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; word-spacing: 0px; float: none; display: inline !important; white-space: normal; orphans: 2; background-color: rgb(255, 255, 255); -webkit-text-stroke-width: 0px;\">µ</span>₁≠<span style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 12px; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; word-spacing: 0px; float: none; display: inline !important; white-space: normal; orphans: 2; background-color: rgb(255, 255, 255); -webkit-text-stroke-width: 0px;\">µ</span>₂</span><br />\n <br />\n where µ1 and µ2  stand for mean change from Baseline in TCD flow velocity at Week 24 in voxelotor and placebo groups, respectively.<br />\n For the secondary efficacy endpoint of percentage conversion to abnormal TCD category, assuming 35% of participant in the placebo group have experienced a TCD flow velocity > 200 cm/sec by Week 96, a hazard ratio of 0.5 between voxelotor group and placebo, a fixed follow up time of up to 96 weeks<br />\n for each participant, and an overall 20% drop out rate, a total of 49 events is expected. This provides approximately 65% power for a log-rank test at a two-sided significance level of 5% and approximately 75% power at a two-sided significance level of 10% (PASS version 11).<br />\n  </div>\n<div>\n <u>Efficacy Analyses</u><br />\n The primary analysis of change in TCD flow velocity from Baseline to Week 24 will be performed using a mixed model for repeated measures (MMRM). Independent variables will include treatment, study visit, treatment by study visit interaction, and randomization stratification factors (ie, HU use, age, Screening TCD flow velocity, and geographic region). Within-subject variability will be modeled using an unstructured covariance matrix.<br />\n The secondary endpoints will be analyzed as described below.</div>\n<ul>\n <li>\n ï‚·    Change from Baseline endpoints:\n <ul>\n <li>\n   Change in TCD flow velocity from Baseline to Week 48 and Week 96 will be analyzed with a similar MMRM as described for the primary efficacy endpoint (change from Baseline in TCD flow velocity at Week 24).</li>\n <li>\n ​Change in Hb and clinical measures of hemolysis (unconjugated bilirubin, % reticulocytes, absolute reticulocyte, and LDH) from Baseline at Week 24, Week 48, and Week 96 will be analyzed with a similar approach.</li>\n </ul>\n </li>\n <li>\n ​TCD responder endpoint:\n <ul>\n <li>\n   The TCD responder endpoint, defined as a TCD flow velocity reduction from Baseline ≥ 15 cm/sec at a given timepoint, eg, Week 24, Week 48, or Week 96, will be analyzed using an exact Cochran-Mantel-Haenszel (CMH) general association test stratified by the randomization stratification factors for the treatment difference between voxelotor and placebo.</li>\n </ul>\n </li>\n <li>\n ​Time to events endpoints:\n <ul>\n <li>\n <div>\n For the incidence of conversion to abnormal TCD, the Kaplan-Meier method will be used to estimate the landmark rates and the associated 95 % confidence intervals in the voxelotor and placebo groups at Week 24, Week 48, and Week 96. A log-rank test stratified for the randomization stratification factors will be used to test the difference between voxelotor and placebo groups. A Cox proportional hazard model may be used to estimate the hazard ratio, as appropriate. Reversion from conditional to normal TCD at Week 24, Week 48, and Week 96 will be analyzed using a similar approach.</div>\n </li>\n </ul>\n </li>\n</ul>\n<div>\n ​<u>Safety and Tolerability Analyses</u><br />\n Safety analysis will be performed on all participants receiving at least one dose of study drug. Adverse events will be classified according to the Medical Dictionary for Regulatory Activities (MedDRA). The incidence of treatment-emergent adverse events (TEAEs), defined as an event that occurs on or after Day 1 of study treatment or the worsening of a preexisting condition on or after Day 1 of study treatment, will be tabulated by System Organ Class (SOC), preferred term, severity,<br />\n and relationship to study drug. Changes in laboratory parameters (hematology, serum chemistry, and liver function tests) and vital signs (eg, blood pressure [BP], pulse, and body temperature) over time will be summarized descriptively. SCD-related AEs will be collected and summarized separately (including<br />\n vaso-occlusive crisis [VOC], acute chest syndrome, osteonecrosis, priapism, etc.) Pharmacokinetic Analyses PPK analysis will consist of all participants who receive active study drug and have at least one measured concentration at a scheduled PK time point after the start of dosing. If any participants are found to be noncompliant with respect to dosing or have incomplete data, protocol deviations, or clinical events that affect PK, a decision will be made on a case-by-case basis as to their inclusion in the analysis.<br />\n Participants in this population will be used for all PK summaries. PPK analyses using nonlinear mixed effects modeling will be performed to characterize voxelotor PK in plasma and whole blood. The influence of demographic covariates (such as body weight, height, age, gender) on voxelotor PK parameters (ie, clearance [CL] and volume of distribution) will be investigated. If appropriate, the voxelotor PK data may be pooled with PK data from other studies. Continuous variables will be descriptively summarized using mean, standard deviation (SD), coefficient of variation (CV%, as appropriate), median, minimum, maximum, and, as appropriate,<br />\n geometric mean. Categorical variables will be descriptively summarized by presenting the number (frequency) and percentage in each category.</div>\n
      • study_title<p>\n A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Voxelotor (GBT440) in Pediatric Participants with Sickle Cell Disease (HOPE Kids 2)</p>\n
      • laymans_summary<p>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial,helvetica,sans-serif;\">This application concerns a Phase 3 pediatric study (GBT440-032) in which it is proposed to show the effect of voxelotor compared to placebo on the transcranial doppler (TCD) time averaged maximum of the mean velocity (TAMMV) arterial cerebral blood flow at 24 weeks in sickle cell disease (SCD) participants ≥ 2 to < 15 years of age with conditional (170 cm/sec to < 200 cm/sec) TCD velocity. </span></span></p>\n<p>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial,helvetica,sans-serif;\">Voxelotor (formerly known as GBT440) is an orally administered small molecule that inhibits HbS polymerization by allosterically modifying hemoglobin-oxygen (Hb-O2) affinity and is being developed for the treatment of sickle cell disease (SCD). Voxelotor was designed to bind to HbS with preferential partitioning into RBCs. It binds covalently and reversibly via Schiff base to the N-terminal valine of the Hb α chain (ie, a single voxelotor molecule binding per HbS tetramer in a 1:1 stoichiometry) and allosterically (Eaton, 1999) increases HbS oxygen (O2) affinity (Oksenberg, 2016), stabilizing the oxyHb state and inhibiting polymerization (Oksenberg, 2016). The voxelotor binding site is distant from heme pockets and therefore it can increase O2 affinity without sterically blocking the release of O2.</span></span></p>\n<p>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial,helvetica,sans-serif;\">Details regarding GBT’s clinical development program for SCD are available in the most current version of the Investigator’s Brochure (Version 7.1). As of 05 November 2019, a total of 24 clinical development studies (5 studies in SCD, 2 studies in idiopathic pulmonary fibrosis (IPF), 15 clinical pharmacology studies, and 1 study of healthy participants under hypoxic conditions) and the expanded access program (which includes 1 clinical study) have enrolled approximately 823 unique participants. The 823 participants consist of 379 participants with SCD (257 adults and 122 pediatric participants), 378 healthy participants (including participants with severe renal impairment [not on dialysis] and participants with hepatic impairment), 43 adult participants with IPF, 23 participants from the expanded access program (6 adolescents and 17 adults), 15 participants from the GBT sponsored expanded access protocol, and 8 participants from single-patient investigational new drug (IND) access.</span></span></p>\n<p style=\"text-align: justify;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial,helvetica,sans-serif;\"><span lang=\"EN-GB\">Study GBT440-032 consists of 3 periods:</span></span></span></p>\n<p style=\"text-align: justify;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial,helvetica,sans-serif;\"><span lang=\"EN-GB\">• Screening: up to 35 days prior to randomization</span></span></span></p>\n<p style=\"text-align: justify;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial,helvetica,sans-serif;\"><span lang=\"EN-GB\">• Treatment: 96 weeks</span></span></span></p>\n<p style=\"text-align: justify;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial,helvetica,sans-serif;\"><span lang=\"EN-GB\">• Follow-Up: 28 days (4 weeks) after the last dose</span></span></span></p>\n<p style=\"text-align: justify;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial,helvetica,sans-serif;\"><span lang=\"EN-GB\">Approximately 224 participants aged ≥ 2 to < 15 years will be randomized 1:1 to voxelotor or placebo.</span></span></span></p>\n<p style=\"text-align: justify;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial,helvetica,sans-serif;\"><span lang=\"EN-GB\">Participants ≥ 12 years old will be administered a fixed dose of voxelotor 1500 mg per day. Participants younger than 12 years of age will receive voxelotor at a weight-based (1500 mg-equivalent) dose. </span></span></span></p>\n<p style=\"text-align: justify;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial,helvetica,sans-serif;\"><span lang=\"EN-GB\">At least 15 participants from 2 years to < 4 years of age will be enrolled. Administration of voxelotor will be initiated in participants < 4 years or age after the DSMB has reviewed safety and PK data from at least 12 participants < 30 kg treated with voxelotor for at least 28 days. These data for at least 12 participants may be generated from any voxelotor clinical studies.</span></span></span></p>\n<p style=\"text-align: justify;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial,helvetica,sans-serif;\"><span lang=\"EN-GB\">Following completion of study treatment, eligible participants will be given the option to enroll in an open label extension study (under a separate protocol) to receive voxelotor.</span></span></span></p>\n
      • short_titleHOPE Kids 2
      • protocol_noECCT/20/11/05
      • version_no2
      • date_of_protocol05-12-2019
      • study_drugVoxelotor (GBT440)
      • disease_conditionInfants with Sickle Cell Disease
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameVoxelotor (GBT440)
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressbianca.hibbert@quintiles.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantAnnalien van Heerden
      • declaration_date127-11-2020
      • declaration_principal_investigatorProf.Jessie Githanga_Dr V Nduba_Dr B Ogutu
      • declaration_date227-11-2020
      • placebo_presentYes
      • study_objectives<p>\n <u><strong>Primary Objective</strong></u></p>\n<div>\n The primary objective is to evaluate the effect of voxelotor compared to placebo on the TCD time-averaged mean of the maximum velocity (TAMMV) arterial cerebral blood flow at 24 weeks in SCD participants ≥ 2 to < 15 years of age with conditional (170 to < 200 cm/sec) TCD flow velocity.</div>\n<div>\n  </div>\n<div>\n <u><strong>Secondary Objectives</strong></u></div>\n<div>\n The secondary objectives are to evaluate the effects of voxelotor compared to placebo on:</div>\n<ul>\n <li>\n ï‚·        Change in TCD flow velocity at Week 48 and Week 96</li>\n <li>\n ï‚·        Conversion of TCD category from conditional to abnormal</li>\n <li>\n ï‚·        Reversion of TCD category from conditional to normal</li>\n <li>\n ï‚·        Proportion of participants with TCD response</li>\n <li>\n ï‚·        Change in Hb over time</li>\n <li>\n ï‚·        Change in clinical measures of hemolysis</li>\n</ul>\n<div>\n  </div>\n<div>\n <u><strong>Exploratory Objectives</strong></u></div>\n<div>\n The exploratory objectives will assess the effect of voxelotor compared to placebo on:</div>\n<ul>\n <li>\n ï‚·        Growth (height, weight, and head circumference)</li>\n <li>\n ï‚·        Neuro-cognitive function</li>\n <li>\n ï‚·        Patient reported symptoms and quality of life</li>\n <li>\n ï‚·        Physician assessed change in global health status</li>\n <li>\n ï‚·        Healthcare utilization</li>\n <li>\n ï‚·        Exploratory biomarkers</li>\n</ul>\n<p>\n <u><strong>Safety Objective</strong></u></p>\n<p>\n The safety objective is to assess the safety and tolerability of voxelotor compared to placebo.</p>\n<div>\n  </div>\n<div>\n <u><strong>Pharmacokinetic Objective</strong></u></div>\n<div>\n The pharmacokinetic (PK) objective is to assess the PK of voxelotor as evaluated by PPK analysis.</div>\n
      • principal_inclusion_criteria<p>\n <u><strong>Inclusion Criteria</strong></u></p>\n<div>\n Participants who meet all of the following criteria will be eligible for study enrollment:</div>\n<div>\n 1.   Age ≥ 2 to <15 years at the time of informed caregiver/legal guardian consent</div>\n<div>\n  </div>\n<div>\n 2.   Male or female study participants with SCA (HbSS, HbSβ0 thalassemia genotype)</div>\n<div style=\"margin-left: 40px;\">\n a.   Documentation of SCA genotype is required and may be based on documented history of laboratory testing or must be confirmed by laboratory testing during screening</div>\n<div style=\"margin-left: 40px;\">\n  </div>\n<div>\n 3.   TCD TAMMV arterial cerebral blood flow ≥ 170 to < 200cm/sec during the Screening Period</div>\n<div>\n  </div>\n<div>\n 4.   Hb ≥ 5.5 and ≤ 10.5 g/dL during screening</div>\n<div>\n  </div>\n<div>\n 5.   Participant is in stable clinical condition with stable Hb level near their usual baseline as determined by the investigator</div>\n<div>\n  </div>\n<div>\n 6.   For participants taking HU, the dose of HU (mg/kg) must be stable for at least 90 days prior to signing the informed consent form (ICF) and/or assent form, and with no anticipated need for dose adjustments (other than weight based). For participants not taking HU, no anticipated need for initiation of HU in the opinion of the Investigator</div>\n<div>\n  </div>\n<div>\n 7.   Adequate venous access, in the opinion of the Investigator, to permit monitoring of blood variables including laboratory safety variables and collection of PK samples</div>\n<div>\n  </div>\n<div>\n 8.   Ability to undergo TCD assessment without sedation</div>\n<div>\n  </div>\n<div>\n 9.   If sexually active and female, must agree to abstain from sexual intercourse or to use a highly effective method of contraception throughout the study period and for 30 days after discontinuation of study drug. If sexually active and male, must agree to abstain from sexual intercourse or willing to use barrier methods of contraception throughout the study period and for 30 days after discontinuation of study drug.</div>\n<div>\n  </div>\n<div>\n 10. Females of child-bearing potential are required to have a negative pregnancy test before the administration of study drug.</div>\n<div>\n  </div>\n<div>\n 11. Written informed parental/guardian consent and participant assent (where applicable) has been obtained per IRB/EC policy and requirements, consistent with ICH guidelines.</div>\n
      • principal_exclusion_criteria<p>\n <u><strong>Exclusion Criteria</strong></u></p>\n<div>\n Participants meeting any of the following exclusion criteria will not be eligible for study enrollment:</div>\n<div>\n 1.   Body weight < 5kg at the screening visit</div>\n<div>\n  </div>\n<div>\n 2.   Hospitalization for VOC or acute chest syndrome (ACS) within the 14 days prior to execution of informed consent/assent (see Section 7.2.5.1 for the definition of VOC).</div>\n<div>\n  </div>\n<div>\n 3.   More than 10 VOCs within the past 12 months that required hospitalization, emergency room, or clinic visit</div>\n<div>\n  </div>\n<div>\n 4.   Stroke resulting in focal neurological deficit; previous silent infarcts are permitted.</div>\n<div>\n  </div>\n<div>\n 5.   Known history or findings   suggestive of significant cerebral vasculopathy (eg, moyamoya or significant vasculopathy)</div>\n<div>\n  </div>\n<div>\n 6.   History of seizure disorder</div>\n<div>\n  </div>\n<div>\n 7.   Has been treated with erythropoietin or other hematopoietic growth factors within 28 days of signing informed consent/assent or if, in the opinion of the Investigator, there is an anticipated need for such agents during the study</div>\n<div>\n  </div>\n<div>\n 8.   RBC transfusion therapy (also termed chronic, prophylactic, or preventative transfusion) or has received an RBC transfusion or exchange transfusion for any reason within 90 days of signing the informed consent/assent</div>\n<div>\n  </div>\n<div>\n 9.   Planned initiation of HU prior to the completion of study participation</div>\n<div>\n  </div>\n<div>\n 10. Severe renal dysfunction (estimated glomerular filtration rate [eGFR]< 30 mL/min/1.73 m2 by Schwartz formula)</div>\n<div>\n  </div>\n<div>\n 11. Alanine aminotransferase (ALT) > 4× upper limit of normal (ULN) for age</div>\n<div>\n  </div>\n<div>\n 12. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including severe or unstable pulmonary hypertension</div>\n<div>\n  </div>\n<div>\n 13. Clinically significant bacterial, fungal, parasitic, or viral infection currently requiring or will require therapy.</div>\n<div style=\"margin-left: 40px;\">\n a.   Participants with acute bacterial infection requiring antibiotic use should delay screening until the course of antibiotic therapy has been completed and the infection has resolved, in the opinion of the investigator.</div>\n<div style=\"margin-left: 40px;\">\n  </div>\n<div>\n 14. Known active hepatitis A, B, or C or human immunodeficiency virus (HIV)-positive.</div>\n<div>\n  </div>\n<div>\n 15. Positive test indicative of active malaria infection at screening (Malaria test to be performed only if there is suspicion of active malaria infection).</div>\n<div>\n  </div>\n<div>\n 16. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable)</div>\n<div>\n  </div>\n<div>\n 17. History of malignancy within the past 2 years prior to treatment Day 1 requiring chemotherapy and/or radiation (with the exception of local therapy for non-melanoma skin malignancy)</div>\n<div>\n  </div>\n<div>\n <div>\n 18. Received an investigational drug within 30 days or 5 half-lives, whichever is longer, of the parent/legal guardian signing the ICF</div>\n <div>\n  </div>\n <div>\n 19.  Parent or legal guardian/participants are unlikely to comply with the study procedures</div>\n <div>\n  </div>\n <div>\n 20. Other medical, psychological, or addictive condition that, in the opinion of the Investigator, would: confound or interfere with evaluation of safety, efficacy, and/or PK of the investigational drug; prevent compliance with the study protocol; preclude informed consent; or, render the participant, parent, or caretaker unable/unlikely to comply with the study procedures</div>\n <div>\n  </div>\n <div>\n 21. Use of herbal medications (eg, St. John’s Wort), sensitive CYP3A4 substrates with a narrow therapeutic index, strong CYP3A4 inhibitors, or fluconazole.</div>\n</div>\n
      • primary_end_points<p>\n <u>Primary Endpoint</u></p>\n<div style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 12px; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n The primary efficacy endpoint is the change from Baseline at 24 weeks in TAMMV arterial cerebral blood flow, as measured by TCD. Secondary Endpoints<br />\n The secondary efficacy endpoints are as follows:</div>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 12px; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n Change from Baseline in TCD flow velocity at Week 48 and Week 96 ï‚·       </li>\n <li>\n Incidence of conversion to abnormal TCD flow velocity (≥ 200 cm/sec) over 24, 48, and 96 weeks</li>\n <li>\n Incidence of reversion to normal TCD flow velocity (<170 cm/sec) over 24, 48, and 96 weeks</li>\n <li>\n Proportion of participants with TCD flow velocity reduction ≥ 15 cm/sec at Week 24, Week 48, and Week 96</li>\n <li>\n Change in Hb from Baseline at Week 24, Week 48, and Week 96</li>\n <li>\n Change in clinical measures of hemolysis (unconjugated bilirubin, % reticulocyte, absolute reticulocyte, and lactate dehydrogenase [LDH]) from Baseline at Week 24, Week 48, and Week 96</li>\n</ul>\n<div style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 12px; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <u>Exploratory Endpoints:</u><br />\n The exploratory endpoints are as follows:</div>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 12px; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n ï‚·        Growth and development as assessed by change from Baseline in height, weight, and head circumference</li>\n <li>\n ï‚·        Neurocognitive function assessed by National Institutes of Health (NIH) toolbox for processing speed</li>\n <li>\n ï‚·        Participant fatigue assessed by the Peds QL Multidimensional Fatigue Scale</li>\n <li>\n ï‚·        Number of missed school days (if applicable) due to SCD</li>\n <li>\n ï‚·        Number of missed work days (if applicable) of the primary caregiver due to participant’s SCD</li>\n <li>\n ï‚·        Investigator assessment of change in the overall health condition of the participant assessed with Clinical Global Impression– Change (CGI-C)</li>\n <li>\n ï‚·        Exploratory biomarkers (dense cells, creatinine:albumin ratio assessments)</li>\n <li>\n ï‚·        Healthcare resource utilization (eg, incidence of hospitalizations, emergency room/clinic visits)</li>\n</ul>\n<div style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 12px; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <u>Safety Endpoints</u><br />\n The safety endpoints include adverse events (AEs), clinical laboratory assessments, and vital signs.<br />\n <u>Pharmacokinetic Endpoint</u><br />\n The endpoint is whole blood and plasma voxelotor PK as evaluated by PPK analysis using nonlinear mixed effects modeling.</div>\n<div style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 12px; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n  </div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<h3>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u><span lang=\"EN-GB\" new=\"\" times=\"\">Site 1: Gertrude’s Children’s Hospital, Muthaiga, Nairobi</span></u></span></span></h3>\n<p>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u><span lang=\"EN-GB\" new=\"\" times=\"\">Principle Investigator:  Prof Jessie Githanga</span></u></span></span></p>\n<h3>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">Gertrude’s Children’s Hospital (GCH) is the largest hospital in East and Central Africa dedicated exclusively to the care of children. For over 60 years, the hospital has provided high standards of paediatric care for children from birth to 21 years of age.  The hospital is accredited by the Joint Commission International Accreditation (JCIA) and <span style=\"background: white; padding: 0cm; border: 1pt windowtext; border-image: none; color: rgb(34, 34, 34); mso-border-alt: none windowtext 0cm;\">Safe Care, Netherlands following audits of the hospital facilities. </span></span>GCH <span 000=\"\" 100-bed=\"\" 21=\"\" a=\"\" accreditation=\"\" accredited=\"\" admits=\"\" aids.=\"\" all=\"\" almost=\"\" also=\"\" and=\"\" are=\"\" areas=\"\" as=\"\" aspect=\"\" attends=\"\" average=\"\" baby=\"\" based=\"\" by=\"\" care=\"\" carrying=\"\" chartered=\"\" chest=\"\" children=\"\" clinic.=\"\" clinics=\"\" comprehensive=\"\" cover=\"\" diagnostic=\"\" equipment=\"\" equipped=\"\" every=\"\" fostering=\"\" from=\"\" good=\"\" headed=\"\" health=\"\" healthcare=\"\" hospital=\"\" immunization=\"\" in=\"\" including=\"\" is=\"\" kenya=\"\" laboratory=\"\" lang=\"EN-GB\" manager=\"\" medical=\"\" modern=\"\" nairobi=\"\" non-profit=\"\" of=\"\" offered=\"\" offers=\"\" on=\"\" oncology=\"\" other=\"\" out=\"\" outpatient=\"\" outpatients=\"\" over=\"\" p=\"\" paediatric=\"\" pathologist=\"\" pathology=\"\" patients=\"\" per=\"\" primary=\"\" provision=\"\" qualified=\"\" research=\"\" responsibility=\"\" sans=\"\" service=\"\" services=\"\" several=\"\" source=\"\" span=\"\" specialist=\"\" spread=\"\" supported=\"\" teaching=\"\" technologists.=\"\" testing=\"\" that=\"\" the=\"\" there=\"\" to=\"\" various=\"\" well=\"\" with=\"\" year.=\"\">ified pharmacists manage the hospital pharmacy.  GCH has an up-to-date paediatric imaging facility that is managed by a team of radiologists and qualified radiographers.  Most of the processes at the hospital are fully computerized and supported by a well-integrate Information Technology (IT) Department.   The main hospital in Muthaiga is open 24/7 and offers 24-hour laboratory and pharmacy coverage.  </span></span></span></h3>\n<p style=\"background: white; margin: 0cm 0cm 7.5pt; text-align: justify;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">The Accident and Emergency Department is well equipped to deal with all forms of paediatric emergencies and has a crash cart and crash team on call, 24 hours a day.   There are registered nurses, medical officers and specialists specifically trained in <span style=\"background: white; color: rgb(51, 51, 51); mso-bidi-font-style: italic;\">Emergency Triage Assessment and Treatment (ETAT)</span>.  The Team is fully trained to handle emergencies, including but not limited to <span style=\"background: white; color: rgb(51, 51, 51);\">airway obstruction and other breathing problems; circulatory impairment or shock; severely altered central nervous system function (coma or convulsive seizures); and severe dehydration which require urgent appropriate care to prevent death.</span> </span></span></span></p>\n<p style=\"background: white; margin: 0cm 0cm 7.5pt; text-align: justify;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">The Hospital runs an Institute of Child Health and Research based at the Muthaiga site which is approved by the Nursing Council of Kenya.  The school offers courses in paediatric endocrinology, paediatric phlebotomy, emergency paediatric medicine and several specialised paediatric nursing courses.  The Hospital has an Ethics Review Committee (ERC) that acts independently from the appointing authority, hosting institution, researchers, sponsors and any other stakeholders in its review and decision-making processes.  The ERC is accredited by the National Commission for Science and Technology and Innovation (NACOSTI), an institution mandated to advise the Government on policies and matters relating to the scientific and technological activities and research required for the proper development of the country.   </span></span></span></p>\n<p style=\"background: white; margin: 0cm 0cm 7.5pt; text-align: justify;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">The population served by the hospital is cosmopolitan and English and Kiswahili are the predominantly spoken languages.</span></span></span></p>\n<p style=\"background: white; line-height: 15pt; margin-bottom: 7.5pt;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\" new=\"\" times=\"\">Site Study staff details. </span></span></span></p>\n<p>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">The site has a multidisciplinary study team that comprises specialists and professionals in many fields of medicine including; medical officers, paediatricians, haematologists, oncologists, pathologists, nurses, pharmacists, medical laboratory technologists.  The Team has members who have been trained on the job as study coordinators.  The team members are experienced in clinical trials and have all been trained in Good Clinical Practice and most have successfully participated in several other clinical trials.  </span></span></span></p>\n<p style=\"text-align: justify;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u><span lang=\"EN-GB\">site personnel roles and responsibilities</span></u></span></span></p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u><span lang=\"EN-GB\">Principal Investigator </span></u></span></span></p>\n<p style=\"text-align: justify; text-indent: -18pt; mso-pagination: none; mso-list: l3 level1 lfo5;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">·<span new=\"\" times=\"\">       </span></span><span lang=\"EN-GB\">Prof Jessie Githanga</span></span></span></p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">A qualified haematologist/clinical pathologist, registered by the Kenya Medical Practitioners and Dentists Board (KMPD).  She will be responsible for the overall conduct of the trial at the study site, budgetary negotiations, administrative actions and communication between Institutional Review Boards, and the sponsor and oversight of patient care. She will oversee the recruitment of the subjects and supervision of the staff. </span></span></span></p>\n<p style=\"text-align: justify; line-height: 115%; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u><span lang=\"EN-GB\">Co-Investigator/main coordinator</span></u></span></span></p>\n<p style=\"line-height: 115%; text-indent: -18pt; margin-bottom: 0pt; mso-list: l2 level1 lfo4; mso-add-space: auto; mso-layout-grid-align: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">·<span new=\"\" times=\"\">       </span></span><span lang=\"EN-GB\">Dr. Doreen Karimi Mutua</span></span></span></p>\n<p style=\"line-height: 115%; margin-bottom: 0pt; mso-layout-grid-align: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">A qualified paediatrician, with subspecialty training in paediatric haemato-oncology <span style=\"color: black;\">working at Gertrude’s Children’s Hospital (GCH) and registered by the KMPD.  Dr Mutua </span>will be responsible for <span style=\"color: black;\">clinical care provision</span> of the patients, direct supervision of study <span style=\"color: black;\">staff and will also participate in study recruitment.  Dr Mutua supports PI and has roles that may be delegated such as ethical and sponsor communication and may be delegated related roles. </span></span></span></span></p>\n<p style=\"text-align: justify; margin-top: 12pt; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u><span lang=\"EN-GB\" style=\"color: black; mso-bidi-font-family: Calibri;\">Study Coordinator :</span></u></span></span></p>\n<p style=\"text-align: justify; line-height: 115%; text-indent: -18pt; mso-pagination: none; mso-list: l6 level1 lfo3;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\" style=\"color: black;\">·<span new=\"\" times=\"\">       </span></span><span lang=\"EN-GB\" style=\"color: black; mso-bidi-font-family: Calibri;\">Dr Mercy Kamene</span></span></span></p>\n<p style=\"text-align: justify; line-height: 115%; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\" style=\"color: black; mso-bidi-font-family: Calibri;\">A qualified medical officer, registered by the KMPDB working at Gertrude’s Children’s Hospital (GCH). She will be the main coordinator for the study and will be responsible for day to day management of trial aspects including participant recruitment, follows up, safety monitoring, data entry and maintaining the site files and other study records and may be delegated related roles.  </span></span></span></p>\n<p style=\"text-align: justify; margin-top: 12pt; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u><span lang=\"EN-GB\" style=\"color: black; mso-bidi-font-family: Calibri;\">Study Pharmacists</span></u><span lang=\"EN-GB\" style=\"color: black; mso-bidi-font-family: Calibri;\">:</span></span></span></p>\n<p style=\"text-align: justify; text-indent: -18pt; margin-bottom: 0pt; mso-pagination: none; mso-list: l1 level1 lfo1; mso-add-space: auto;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\" style=\"color: black;\">·<span new=\"\" times=\"\">       </span></span><span lang=\"EN-GB\" style=\"color: black; mso-bidi-font-family: Calibri;\">Dr Samuel Madere</span></span></span></p>\n<p style=\"text-indent: -18pt; margin-left: 36pt; mso-list: l1 level1 lfo1;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">·<span new=\"\" times=\"\">       </span></span><span lang=\"EN-GB\" new=\"\" times=\"\">Dr. Ibrahim Otieno Okich</span></span></span></p>\n<p style=\"text-align: justify; margin-bottom: 0pt; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\" style=\"color: black; mso-bidi-font-family: Calibri;\"> </span></span></span></p>\n<p style=\"text-align: justify; margin-bottom: 0pt; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\" style=\"color: black; mso-bidi-font-family: Calibri;\">Qualified pharmacist, registered by the Pharmacy and Poisoons Board, will be delegated roles of the IP storage and related duties, IP dispensing, processing of import permit for IP and may be delegated related roles.</span></span></span></p>\n<p style=\"text-align: justify; margin-top: 12pt; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u><span lang=\"EN-GB\">Study nurses:</span></u></span></span></p>\n<p style=\"text-align: justify; text-indent: -18pt; mso-pagination: none; mso-list: l5 level1 lfo6;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">·<span new=\"\" times=\"\">       </span></span><span lang=\"EN-GB\">Hannah Wanjiku (assistant study coordinator)</span></span></span></p>\n<p style=\"text-align: justify; text-indent: -18pt; mso-pagination: none; mso-list: l4 level1 lfo2;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">·<span new=\"\" times=\"\">       </span></span><span lang=\"EN-GB\">Felicity Kamundi </span></span></span></p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">A registered nurse, registered by the Nursing Council of Kenya,  will be responsible for co-ordinating the patient visits, patient training and tracking on ePRO diary. The assistant study coordinator will in addition play a role in study coordination. </span></span></span></p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u><span lang=\"EN-GB\">Laboratory Manager:</span></u></span></span></p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">Peninah Chege: </span></span></span></p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">Laboratory manager registered by the Kenya Medical Laboratory Technologists and Technicians Board (KMLTTB) will coordinate laboratory functions, process the import permits for laboratory items, patient and may be delegated related roles.</span></span></span></p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u><span lang=\"EN-GB\">Laboratory technologist/phlebotomist</span></u></span></span></p>\n<p style=\"text-align: justify; text-indent: -18pt; mso-pagination: none; mso-list: l0 level1 lfo7;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">·<span new=\"\" times=\"\">       </span></span><span lang=\"EN-GB\">Charles Muia (technologist)</span></span></span></p>\n<p style=\"text-align: justify; text-indent: -18pt; mso-pagination: none; mso-list: l0 level1 lfo7;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">·<span new=\"\" times=\"\">       </span></span><span lang=\"EN-GB\">Herman Akumu(technologist) </span></span></span></p>\n<p style=\"text-align: justify; text-indent: -18pt; mso-pagination: none; mso-list: l0 level1 lfo7;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">·<span new=\"\" times=\"\">       </span></span><span lang=\"EN-GB\">Joseph Langat (phlebotomist)</span></span></span></p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">Trained laboratory technologists registered by the KMLTTB, and phlebotomist who will obtain specimens from study participants.  The technologists will perform any local laboratory testing where necessary and package specimens for shipping to Central or other local labs.</span></span></span></p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u><span lang=\"EN-GB\">Quality Assurance Officer</span></u></span></span></p>\n<p style=\"text-align: justify; text-indent: -18pt; mso-pagination: none; mso-list: l7 level1 lfo8;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">·<span new=\"\" times=\"\">       </span></span><span lang=\"EN-GB\">Winnie Abuto</span></span></span></p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">The quality assurance officer (nursing background) registered by the Nursing Council of Kenya, will be tasked with ensuring that study documents are quality controlled so that they are </span><span lang=\"EN-GB\" style=\"background: white; color: rgb(34, 34, 34); mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;\">Attributable, Legible, Contemporaneous, Original, and Accurate (ALCOA)</span><span lang=\"EN-GB\"> </span><span lang=\"EN-GB\">in accordance </span><span lang=\"EN-GB\" style=\"line-height: 107%;\">ICH-GCP guidelines</span><span lang=\"EN-GB\">.  She will ensure that staff are alerted to changes in SOPs as necessary.</span></span></span></p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u><span lang=\"EN-GB\">Administrative assistant</span></u></span></span></p>\n<p style=\"text-align: justify; text-indent: -18pt; mso-pagination: none; mso-list: l7 level1 lfo8;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">·<span new=\"\" times=\"\">       </span></span><span lang=\"EN-GB\">Truphena Otinyo</span></span></span></p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><span lang=\"EN-GB\">The Administrative assistant will coordinate and maintain the records of communications with the ERC, assist the main coordinator in patient visit coordination.  She may be delegated related roles.</span></span></span></p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n  </p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u>Site 2: KENYA MEDICAL RESEARCH INSTITUTE-CENTRE FOR RESPIRATORY DISEASE RESEARCH (KEMRI-CRDR)-Clinical Research Annex</u></span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: times new roman,times,serif; font-size: 12px; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: underline; word-spacing: 0px; float: none; display: inline; white-space: normal; orphans: 2; background-color: rgb(255, 255, 255); -webkit-text-stroke-width: 0px;\">Principle Investigator:  Dr. Videlis Nduba</span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">The Kenya Medical Research Institute (KEMRI) is a state corporation established through the Science and Technology (Amendment) Act of 1979, which has since been amended to Science, Technology and Innovation Act 2013 as the national body responsible for carrying out health research in Kenya. KEMRI has grown from its humble beginnings over 40 years ago to become a regional leader in human health research. Our mission is to improve human health and quality of life through research, capacity building, innovation and service delivery.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">KEMRI’s pivotal role in the Health sector can be categorized into:</span></span></p>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Conducting high quality research that informs evidence based policy</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Translating research into best practices</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Capacity building and service delivery for human health.</span></span></li>\n</ul>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">In this regard, KEMRI as the research arm of the Ministry of Health conducts research for health that facilitates the translation of this goal into reality by ensuring the innovative science informs practical applications for enhancement of human health.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">The Scientific and Ethics Review Unit (SERU) is central to research in KEMRI. The Unit’s purpose is to facilitate research with human participants and to protect their rights and welfare. SERU reviews research submissions from KEMRI and non -KEMRI researchers interested in conducting research in Kenya. The Unit ensures that all proposals adhere to scientific and ethical principles that are fundamental to the conduct of research involving human participants.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">KEMRI has 15 research centers with state of the art research facilities and laboratories spread throughout Kenya. Although the Centers have evolved to encompass emerging research needs, they were created based on research areas of expertise.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">CRDR –Clinical Research Annex is one of the research centers located at the Kenyatta National Hospital (KNH) complex. Over the years, the center has developed a critical mass of highly skilled scientists and technical staffs to enable it conduct competitive research and achieve ranking as a center of excellence (CoE) in research for health. Its mission is to apply modern science and biotechnology to discover, develop and improve tools and strategies for surveillance, diagnosis, prevention and control of major human diseases in Kenya and the region. Moreover, its mandate is to undertake basic and biotechnology-related research on human diseases and their interaction with the zoonosis field in Kenya, with the overall goal to contribute in the improvement of human health and welfare.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Clinical Research Annex is an outpatient and inpatient facility which caters for subjects attending clinic for study related activities.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">The facility comprises the following;</span></span></p>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Equipped pharmacy with secure storage room for investigational medicinal product (IMP) with lock protection and temperature tracking.</span></span></li>\n</ul>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Laboratory with adequate space, freezer room and a secure storage room. The laboratory is equipped with a biosafety cabinet, refrigerated centrifuge, incubator, -80⁰c freezer, -20⁰c freezer, refrigerator, liquid nitrogen tank and ELISA reader and supported by qualified staff. Varieties of test done include; QuantiFERON plus assays. PBMC separation, plasma and serum separation and sample collection for pharmacodynamics and pharmacokinetics.</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Inpatient facility with well-equipped male and female wards.</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Nursing station- Procedure Room with vital signs monitors and crash cart for emergent care if needed.</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Clinician examination rooms -Equipped with stethoscope, patient trolley and other items required for physical examination.</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Quality assurance room for securing records with double lock protection.</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Computerized systems for data capture supported by a well-integrated information technology (IT) team.</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Conference room for training and meetings specifically for researchers.</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Ample space for hosting clinical research associates (CRAs) during site monitoring visits.</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Back-up generator in the event of power outage.</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Inpatient department that caters for patients in study requiring close monitoring. It comprises of male and female wards,kitchen,clinicians room</span></span></li>\n</ul>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u>SITE STAFF DETAILS</u></span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">The site has a study team that comprises specialists and professionals in many fields of medicine and social sciences, the team members are experienced in clinical trials and have all been trained in Good Clinical Practice and most have successfully participated in several other clinical trials and delegated by principal investigator.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Site Personnel Roles and Responsibilities</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u>Principal Investigator</u></span></span></p>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Dr. Videlis Nduba</span></span></li>\n</ul>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">A qualified epidemiologist and medical doctor registered by the Kenya Medical Practitioners and Dentists Board (KMPDB). He is responsible for ensuring that clinical trial studies are conducted according to the signed investigator statement, the investigational plan, and applicable regulations; IMP oversight, protecting the rights, safety and welfare of the subjects under the investigator’s care. Additionally, he is charged with other responsibilities including budgetary negotiations, ensuring adequate resources for the trial, compliance with the approved protocol, provision of progress reports according to Institutional Review Boards (IRB) as required and communication between IRBs and the sponsor.. He will oversee the recruitment of the subjects and supervision of the staff.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u>Co -Investigator</u></span></span></p>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Dr. Grace Kaguthi</span></span></li>\n</ul>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">A qualified Medical Officer/Clinical Research Scientist registered by the KMPDB. She is responsible for ensuring adequate resources are availed for the trial, provision of medical care to study patients, communication with IRB/EC (proving progress reports and safety reporting), direct supervision of study staff and also participates in study recruitment. She supports the PI and has roles that may be delegated to her including but not limited to ethical and sponsor communication.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u>Study Coordinator/Sub-PI</u></span></span></p>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Dr. Jacqueline Mirera-Medical Officer</span></span></li>\n</ul>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">A qualified medical officer, registered by the KMPDB. She is the main study coordinator for the study and is responsible for day to day management of clinical trial aspects including but not limited to medical assessment and study- related medical decisions, participant recruitment, ensuring review of informed consent forms, review and follow up of patients and their records. She is also charged with safety monitoring including reviewing and submission of SAE reports, data entry, maintenance of site files and other study records may have other delegated roles.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u>Sub investigator</u></span></span></p>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Dr Fridah Mwendia-Medical Officer</span></span></li>\n</ul>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">A qualified medical officer, registered by the KMPDB. She will be sub-investigator for the study and is responsible for day to day management of trial aspects including participant recruitment, ensuring review of informed consents, review patients and records, review patients lab results. patients follow- up, safety monitoring including reviewing and submission of SAE reports, provide progress report according to IRB as required, ethics and regulatory communication, data entry and maintaining the site files and other study records and may be delegated related roles.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u>Study Pharmacists</u></span></span></p>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Dr Julius Kiuri-Pharmacist</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Dr Ruth Njoroge-Pharmacist</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Ezekiel Muinde-Pharmaceutical Technologist</span></span></li>\n</ul>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">The aforementioned are qualified pharmacy practitioners duly registered by Kenya Pharmacy and Poisons Board. They will be responsible for maintaining records for the IMP delivery to the trial site, dispensing and accountability, reception and storage. Additionally, responsible for checking on subject compliance to IMP, its return and destruction, IMP-related data query response and processing of import permit.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u>Clinical Officer</u></span></span></p>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Carolyne Epiche-Clinical Officer</span></span></li>\n</ul>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">A qualified Clinical officer registered by Clinical Officers Council. She is responsible for obtaining informed consent from the subjects, informing participant about trial procedures, trial visit requirements, reviewing of laboratory test results, medical assessment and trial related medical decisions. Additionally, she is charged with safety reporting, completing and correcting source documents of the participant, data entry and resolving data queries.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u>Study Nurse</u></span></span></p>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Purity Vuchete-Assistant study coordinator</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Stella Nthambi</span></span></li>\n</ul>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">The aforementioned are qualified nursing practitioners duly registered by the Nursing Council of Kenya. Their responsibilities include: conducting informed consent process, documenting particulars (demographics, contact details etc) of participants, taking and recording vital signs, taking medical history of participants, training participants on any requisite study related activities and community mobilization.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u>Laboratory Technologist</u></span></span></p>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Erick Njuki-Lab Technologist</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Everlyne Abisinwa-Lab Technologist</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Wilfred Murithi-Laboratory Scientist</span></span></li>\n</ul>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">The aforementioned are qualified laboratory practitioners duly registered by the Kenya Medical Laboratory Technologists and Technicians Board (KMLTTB). Their main responsibilities include coordinating laboratory related activities; process the import and export permits for laboratory items, sample collection, separation of plasma/serum, peripheral blood mononuclear cells (PBMC) processing, QuantiFERON plus assays, freezing of samples. packaging and shipping and coordinating calibration of equipment.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u>Quality Assurance/Quality Control Officers</u></span></span></p>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Elizabeth Chirchir-Counselling Psychologist</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Milka Mueni-Molecular Biologist</span></span></li>\n</ul>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">The quality assurance (QA) team will be tasked with reviewing informed consent documents to ensure thorough and ethical process, maintaining the regulatory binders with essential documents, quality control checks, ethics and regulatory communication, source data verification, training staff on standard operating procedures related to QA, maintenance of patient’s files, archival of study files and facilitate study monitoring and evaluation visits.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u>Community Health officers</u></span></span></p>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Inviolata Sakwa-Laboratory Technologist</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Charity Wambua-Public health specialist</span></span></li>\n</ul>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">The community health team will be responsible for engagement and sensitization of relevant stake holders to align the community with the study agenda. This will involve identification and screening of potential participants, recruitment and retention of study participants, participant defaulter tracing, participant log in /log out and travel reimbursement.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u>Data officers</u></span></span></p>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Collins Mugenya-ICT officer</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Japhet Lelei-ICT Officer</span></span></li>\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Magret Gikuni-ICT officer</span></span></li>\n</ul>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">The data management team will be responsible for data entry to electronic CRF, maintenance of ICT systems, training on any study related device if any and IT support.</span></span></p>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\"><u>Administrative Officer</u></span></span></p>\n<ul style=\"padding: 0px 40px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <li>\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">Carolyne Gathoni</span></span></li>\n</ul>\n<p style=\"text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 14.06px; font-style: normal; font-variant: normal; font-weight: 700; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\">\n <span style=\"font-family: times new roman,times,serif;\"><span style=\"font-size: 12px;\">The administrative officer will coordinate participant reimbursement, procurement of site supplies, keep track of study expenditure, maintain the records and assist the study coordinator in patient visit coordination.</span></span></p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n  </p>\n<p style=\"text-align: justify; mso-pagination: none;\">\n  </p>\n
      • other_details_explanation<p>\n Not Applicable</p>\n
      • other_details_regulatory_notapproved<p>\n  </p>\n<p>\n  </p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width: 100%;\" width=\"100%\">\n <tbody>\n <tr>\n <td style=\"width: 29.72%; height: 64px;\">\n <p align=\"left\">\n <strong><u>Country</u></strong></p>\n </td>\n <td style=\"width: 38.28%; height: 64px;\">\n <p align=\"center\">\n <strong><u>Submission Status</u></strong></p>\n </td>\n <td style=\"width: 28.88%; height: 64px;\">\n <p align=\"center\">\n <strong><u>Regulatory Authority Decision / Date</u></strong></p>\n </td>\n <td style=\"width: 3.12%; height: 64px;\">\n <p align=\"left\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 29.72%; height: 54px;\">\n <p align=\"left\">\n <strong>France</strong></p>\n <p align=\"left\">\n Agence Nationale de Sécurité du Médicament et des produits de santé</p>\n </td>\n <td style=\"width: 38.28%; height: 54px;\">\n <p align=\"center\">\n To be submitted</p>\n </td>\n <td style=\"width: 28.88%; height: 54px;\">\n <p align=\"center\">\n [N/A]</p>\n </td>\n <td style=\"width: 3.12%; height: 54px;\">\n <p align=\"left\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 29.72%; height: 54px;\">\n <p align=\"left\">\n <strong>Italy</strong></p>\n <p align=\"left\">\n Agenzia italiana del farmaco</p>\n </td>\n <td style=\"width: 38.28%; height: 54px;\">\n <p align=\"center\">\n To be submitted</p>\n </td>\n <td style=\"width: 28.88%; height: 54px;\">\n <p align=\"center\">\n [N/A]</p>\n </td>\n <td style=\"width: 3.12%; height: 54px;\">\n <p align=\"left\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 29.72%; height: 92px;\">\n <p align=\"left\">\n  </p>\n </td>\n <td style=\"width: 38.28%; height: 92px;\">\n  </td>\n <td style=\"width: 28.88%; height: 92px;\">\n <p align=\"center\">\n  </p>\n </td>\n <td style=\"width: 3.12%; height: 92px;\">\n <p align=\"left\">\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n <strong><u>-----------------------------------------------------------------------------------------------------------------------------------</u></strong></p>\n<p>\n <strong>Countries Outside of the European Economic Area</strong></p>\n<p>\n An application for clinical trial authorization is planned to be submitted or has been submitted to the National Competent Authorities of the following countries:</p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width: 603px;\" width=\"603\">\n <thead>\n <tr>\n <th style=\"width: 186px;\">\n <p align=\"left\">\n <strong><u>Country</u></strong></p>\n </th>\n <th style=\"width: 228px;\">\n <p align=\"center\">\n <strong><u>Submission Status</u></strong></p>\n </th>\n <th style=\"width: 189px;\">\n <p align=\"center\">\n <strong><u>Regulatory Authority Decision / Date</u></strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td style=\"width: 186px;\">\n <p align=\"left\">\n  </p>\n </td>\n <td style=\"width: 228px;\">\n  </td>\n <td style=\"width: 189px;\">\n <p align=\"center\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 186px;\">\n <p align=\"left\">\n <strong>Ghana</strong></p>\n <p align=\"left\">\n Food and Drugs Authority</p>\n </td>\n <td style=\"width: 228px;\">\n <p align=\"center\">\n To be submitted</p>\n </td>\n <td style=\"width: 189px;\">\n <p align=\"center\">\n [N/A]</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 186px;\">\n <p align=\"left\">\n <strong>Kenya</strong></p>\n <p align=\"left\">\n Ministry of Health Pharmacy and Poisons Board</p>\n </td>\n <td style=\"width: 228px;\">\n <p align=\"center\">\n To be submitted</p>\n </td>\n <td style=\"width: 189px;\">\n <p align=\"center\">\n [N/A]</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 186px;\">\n <p align=\"left\">\n  </p>\n </td>\n <td style=\"width: 228px;\">\n  </td>\n <td style=\"width: 189px;\">\n <p align=\"center\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 186px;\">\n <p align=\"left\">\n <strong>Oman</strong></p>\n <p align=\"left\">\n (EC submission only)</p>\n </td>\n <td style=\"width: 228px;\">\n <p align=\"center\">\n [N/A]</p>\n </td>\n <td style=\"width: 189px;\">\n <p align=\"center\">\n [N/A]</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 186px;\">\n <p align=\"left\">\n <strong>Saudi Arabia</strong></p>\n <p align=\"left\">\n Saudi Food and Drug Authority</p>\n </td>\n <td style=\"width: 228px;\">\n <p align=\"center\">\n Submitted</p>\n </td>\n <td style=\"width: 189px;\">\n <p align=\"center\">\n Pending Review</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 186px;\">\n <p align=\"left\">\n <strong>United States</strong></p>\n <p align=\"left\">\n Food and Drug Administration</p>\n </td>\n <td style=\"width: 228px;\">\n <p align=\"center\">\n IND submitted</p>\n </td>\n <td style=\"width: 189px;\">\n <p align=\"center\">\n Key elements of protocol – No objections</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 186px;\">\n <p align=\"left\">\n  </p>\n </td>\n <td style=\"width: 228px;\">\n <p align=\"left\">\n  </p>\n </td>\n <td style=\"width: 189px;\">\n <p align=\"left\">\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_approved<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"border: 1px dotted rgb(211, 211, 211); border-image: none; width: 603px; text-align: left; color: rgb(34, 34, 34); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Arial,Verdana,sans-serif; font-size: 12px; font-style: normal; font-variant: normal; font-weight: 400; text-decoration: none; word-spacing: 0px; white-space: normal; orphans: 2; -webkit-text-stroke-width: 0px;\" width=\"603\">\n <thead>\n <tr>\n <th style=\"border: 1px dotted rgb(211, 211, 211); border-image: none; width: 186px;\">\n  </th>\n <th style=\"border: 1px dotted rgb(211, 211, 211); border-image: none; width: 228px;\">\n  </th>\n <th style=\"border: 1px dotted rgb(211, 211, 211); border-image: none; width: 189px;\">\n  </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td style=\"border: 1px dotted rgb(211, 211, 211); border-image: none; width: 186px;\">\n  </td>\n <td style=\"border: 1px dotted rgb(211, 211, 211); border-image: none; width: 228px;\">\n  </td>\n <td style=\"border: 1px dotted rgb(211, 211, 211); border-image: none; width: 189px;\">\n  </td>\n <td style=\"border: 1px dotted rgb(211, 211, 211); border-image: none; width: 189px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width: 100%;\" width=\"100%\">\n <tbody>\n <tr>\n <td style=\"width: 29.72%; height: 64px;\">\n <p align=\"left\">\n <strong><u>Country</u></strong></p>\n </td>\n <td style=\"width: 38.28%; height: 64px;\">\n <p align=\"center\">\n <strong><u>Submission Status</u></strong></p>\n </td>\n <td style=\"width: 28.88%; height: 64px;\">\n <p align=\"center\">\n <strong><u>Regulatory Authority Decision / Date</u></strong></p>\n </td>\n <td style=\"width: 3.12%; height: 64px;\">\n <p align=\"left\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 29.72%; height: 92px;\">\n <p align=\"left\">\n <strong>United Kingdom</strong></p>\n <p align=\"left\">\n Medicines and Healthcare Products Regulatory Agency</p>\n </td>\n <td style=\"width: 38.28%; height: 92px;\">\n <p align=\"center\">\n Approved</p>\n </td>\n <td style=\"width: 28.88%; height: 92px;\">\n <p align=\"center\">\n 21 March 2018</p>\n </td>\n <td style=\"width: 3.12%; height: 92px;\">\n <p align=\"left\">\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n <strong><u>-----------------------------------------------------------------------------------------------------------------------------------</u></strong></p>\n<p>\n <strong>Countries Outside of the European Economic Area</strong></p>\n<p>\n An application for clinical trial authorization is planned to be submitted or has been submitted to the National Competent Authorities of the following countries:</p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width: 603px;\" width=\"603\">\n <thead>\n <tr>\n <th style=\"width: 186px;\">\n <p align=\"left\">\n <strong><u>Country</u></strong></p>\n </th>\n <th style=\"width: 228px;\">\n <p align=\"center\">\n <strong><u>Submission Status</u></strong></p>\n </th>\n <th style=\"width: 189px;\">\n <p align=\"center\">\n <strong><u>Regulatory Authority Decision / Date</u></strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td style=\"width: 186px;\">\n <p align=\"left\">\n <strong>Egypt</strong></p>\n <p align=\"left\">\n Egyptian Ministry of Health, Central Dicrectorate of Research and Health Development</p>\n </td>\n <td style=\"width: 228px;\">\n <p align=\"center\">\n Approved</p>\n </td>\n <td style=\"width: 189px;\">\n <p align=\"center\">\n 3 October 2018</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 186px;\">\n  </td>\n <td style=\"width: 228px;\">\n  </td>\n <td style=\"width: 189px;\">\n <p align=\"center\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 186px;\">\n <p align=\"left\">\n <strong>Nigeria</strong></p>\n <p align=\"left\">\n National Agency for Food and Drug Administration and Control</p>\n </td>\n <td style=\"width: 228px;\">\n <p align=\"center\">\n Approved</p>\n </td>\n <td style=\"width: 189px;\">\n <p align=\"center\">\n 06 July 2020</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 186px;\">\n  </td>\n <td style=\"width: 228px;\">\n  </td>\n <td style=\"width: 189px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n Not Applicable</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable</p>\n
      • estimated_durationApproximately 105 weeks.
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states10
      • number_of_sites4
      • multi_country_listFrance\nItaly\nUnited Kingdom\nEgypt\nGhana\nKenya\nNigeria\nOman\nSaudi Arabia\nUnited States
      • data_monitoring_committeeYes
      • total_enrolment_per_siteEnrollment will be competitive over 3 sites in Kenya\nExpected 18 Participants to be enrolled per site.
      • total_participants_worldwide224
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJessie
      • investigator1_middle_nameNyokabi
      • investigator1_family_nameGithanga
      • investigator1_qualificationMBChB, MMED (Path) (UON), FCPath ECSA
      • investigator1_professional_addressGertrude’s Children’s Hospital, Muthaiga, Muthiga Road, Off Thika Superhighway, Nairobi
      • investigator1_telephone+254 721245721
      • investigator1_emailjessie.githanga@uonbi.ac.ke
      • organisations_transferred_Yes
      • number_participantsExpected 54 Participants to be Enrolled\nExpected 120 Participants to be Screened
      • notification<p>\n Xcene Research on behalf of Global Blood therapeutics (GBT) hereby wishes to notify the Kenya Pharmacy and Poisons Board of the activation of an additional site (KEMRI CRDR SIAYA SITE 11001) to the above referenced protocol which received regulatory approval on 3MAR2021 with ECCT number: KPPB/ECCT/20/11/05/2021(033) and Annual Approval on 7JUN2022 with Ref. No. APL/4/2021-ECCT/20/11/05/2022(153).</p>\n<p>\n Because the Sponsor initially projected three Kenyan sites to be sufficient for recruitment, the aforementioned site was instructed to remain inactivated until the study's enrollment rate could be assessed. The Sponsor has since determined the enrollment rate to be slower than anticipated due to the strict TCD inclusion criteria and has requested the aforementioned site to be activated to fulfil recruitment needs. We’d like to request for regulatory approval to begin activation of site activities and patient recruitment. In support of this application, the supporting documents have been uploaded for your review.</p>\n
      • approval_date03-03-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted01-08-2022
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe application has been approved by the experts
      • final_report
      • implication_results<p>\n In children with SCD at a higher risk of stroke, the study demonstrated that voxelotor improves cerebral blood flow, increases hemoglobin levels and decreases markers of hemolysis. However, there was an imbalance in the rate Vaso-occlusive crisis rate and mortality rate in the voxelotor treated patients, which requires further assessment.</p>\n
      • quantity_imported11001: 319, 11003: 950, 11004: 615, 11005: 763
      • quantity_dispensed11001: 73, 11003: 256, 11004: 30, 11005: 140
      • quantity_destroyed11001: 0, 11003: 712, 11004: 315, 11005: 615
      • quantity_exported11001: 0, 11003: 0, 11004: 0, 11005: 0
      • balance_site11001: 323, 11003: 940, 11004: 0, 11005: 148
      • final_date2025-07-16 11:46:42
      • modified2025-09-04 16:26:52
      • created2018-05-09 12:24:02
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id424
        • application_id674
        • given_nameJessie
        • middle_nameNyokabi
        • family_nameGithanga
        • qualificationMBChB, MMED (Path) (UON), FCPath ECSA
        • professional_addressGertrude’s Children’s Hospital, Muthaiga, Muthiga Road, Off Thika Superhighway, Nairobi
        • telephone+254 721245721
        • emailjessie.githanga@uonbi.ac.ke
        • created2018-05-09 12:27:54
        • modified2022-08-01 16:46:58
      • 1(array)
        • id425
        • application_id674
        • given_nameVidelis
        • middle_name
        • family_nameNduba
        • qualificationPHD (Epidemiology), MMed, MBChB
        • professional_addressKEMRI/CRDR Clinical Research Annex Hospital Road next to Kenyatta National Hospital Past Government Chemist PO Box 47855-00100 Nairobi, Kenya
        • telephone+254724522474
        • emailvnduba@gmail.com
        • created2018-05-09 12:36:08
        • modified2022-08-01 16:46:58
      • 2(array)
        • id557
        • application_id674
        • given_nameBernhards
        • middle_nameRagama
        • family_nameOgutu
        • qualificationMMed, MBChB
        • professional_addressStrathmore University Medical Centre Madaraka Estate Ole Sangale rd, Nairobi, 59857-00200, Kenya
        • telephone+254 733 812 613
        • emailOgutu6@gmail.com
        • created2020-05-22 13:18:06
        • modified2022-08-01 16:46:58
    • SiteDetail(array)
      • 0(array)
        • id541
        • application_id674
        • county_id47
        • site_nameGertrude’s Children’s Hospital
        • physical_addressMuthaiga, Muthiga Road, Off Thika Superhighway, Nairobi
        • contact_details+254 0721245721
        • contact_personProf Jessie Githanga
        • site_capacity(null)
        • misc(null)
        • created2018-05-09 12:27:54
        • modified2022-08-01 16:46:58
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id779
        • application_id674
        • county_id47
        • site_nameKEMRI/CRDR Clinical Research Annex
        • physical_addressHospital Road next to Kenyatta National Hospital Past Government Chemist PO Box 47855-00100 Nairobi, Kenya
        • contact_details+254 724522474
        • contact_personDr. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2020-06-09 21:21:40
        • modified2022-08-01 16:46:58
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
        • id780
        • application_id674
        • county_id47
        • site_nameStrathmore University Medical Centre
        • physical_addressMadaraka Estate Ole Sangale rd, Nairobi, 59857-00200, Kenya
        • contact_details+254 733812613
        • contact_person Dr Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2020-06-09 21:21:40
        • modified2022-08-01 16:46:58
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 3(array)
        • id1296
        • application_id674
        • county_id41
        • site_nameKEMRI/CRDR Siaya
        • physical_addressSiaya County Referral Hospital Road
        • contact_details+254 724522474
        • contact_personDr. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2022-08-01 16:08:08
        • modified2022-08-01 16:46:58
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id339
        • application_id674
        • sponsorGlobal Blood Therapeutics, Inc.
        • sponsor_typeResearch Institution
        • contact_personDan Rudin
        • address171 Oyster Point Blvd, Suite 300 South San Francisco, CA 94080 United States of America
        • telephone_number(781) 227-3122
        • fax_number
        • cell_number(781) 227-3122
        • email_addressdrudin@gbt.com
        • created2018-05-09 12:27:54
        • modified2022-08-01 16:46:58
  • 3(array)
    • Application(array)
      • id1330
      • user_id263
      • trial_status_id4
      • abstract_of_study<div>\n <div>\n Bifidobacteria are gram-positive, heterofermentative, anaerobic bacteria that colonize the newborn gut within the first days and weeks of life. They are often the most abundant bacterial genus in a breast-fed infant’s intestinal flora. B. infantis metabolizes Human milk oligosaccharides (HMOs) and produces short chain fatty acids (SCFA) that are thought to play an important role in nutrition and immune development, stimulating anti-inflammatory and inhibiting pro-inflammatory responses [Halloran 2019; Henrick 2021].</div>\n <div>\n  </div>\n <div>\n B. infantis Bi-26 strain is a nutritional probiotic intervention that will be evaluated in this trial for its ability to improve weight gain and health outcomes of underweight infants with WAZ <-2 who have been hospitalized with acute illness.</div>\n <div>\n  </div>\n <div>\n Clinical study data in the United States (US) have shown that B. infantis strain EVC001 colonizes the gut and is associated with significant changes to fecal microbiome composition in healthy breast-fed infants [Frese 2017; Henrick 2019]. Supplementation of B. infantis EVC001 has been associated with a reduction in pro-inflammatory cytokines [Henrick 2019]. Similar observations have been reported for preterm infants given B. infantis EVC001 [Nguyen 2021].</div>\n <div>\n  </div>\n <div>\n In a pilot trial evaluating B. infantis EVC001 supplementation in Bangladesh in hospitalized 2-to 6-month-old infants with SAM, i.e., weight-for-length z score [WLZ] <-3, researchers observed that daily supplementation with B. infantis for 4 weeks was associated with B. infantis colonization and an increase in WAZ [Barratt 2022].</div>\n <div>\n  </div>\n <div>\n A number of B. infantis strains, including Bi-26, have been designated as generally recognized as safe (GRAS) based on review by a panel of independent experts in the field. Furthermore, the US Food and Drug Administration (FDA) did not have questions about the GRAS determination of Bi-26 (GRN 985). In the US, the GRAS determination and the FDA no question letter allow the use of Bi-26 under its intended conditions of use (healthy term infants) in infant formula. The strain bearing the GRAS designation can also be used in dietary supplements, including those for infants.</div>\n <div>\n  </div>\n <div>\n In low-income countries, B. infantis strain Bi-26, evaluated in this study, could potentially be used as a dietary supplement in underweight infants if the safety and efficacy findings of the previous pilot study are confirmed.</div>\n</div>\n<p>\n  </p>\n
      • study_title<p>\n A Phase 3, randomized, double-blind, placebo-controlled study to evaluate the effect of Bi-26 (strain of Bifidobacterium longum, B. infantis) supplementation versus placebo on weight gain in underweight infants</p>\n
      • laymans_summary<p>\n Poor countries bear a greater burden of children who are born with a weight that is less than it should be for their age. Poor health in the digestive system (gut) can be caused by a poor balance of good bacteria that are thought to play a role in how nutrients are absorbed in the intestines. Good bacteria in a baby’s gut are important in helping the baby grow, develop normally, and be healthier. One of the bacteria, called <em>B. infantis</em>, that is normally found in babies’ guts makes it easier for the baby to digest their mother’s milk and help keep the baby healthy. Babies who have a weight that is less than it should be for their age have less of the <em>B. infantis</em> bacteria, compared to healthy babies. This may cause poor absorption of these nutrients and can lead to babies not being able to gain weight, leading to them becoming underweight and failing to thrive. Providing a dietary supplement with a specific strain of the bacteria known as EVC001 has been shown to boost the friendly bacteria living in the gut and cause significant changes in the composition of the friendly bacteria and its environment in the gut especially in healthy babies who are breastfed. </p>\n<p>\n A small study in Bangladesh tested this strain among babies who were aged between 2 and 6 months and had been admitted to hospital, who were also suffering from severe acute malnutrition. They were given the friendly <em>B. infantis</em> bacteria species as a dietary supplement daily for a period of four weeks. It was found out that this supplementation boosted the friendly bacteria and resulted in the children gaining weight and improving their nutritional weight-for-age Z score (WAZ). We want to study underweight babies who are between 1 and 4 months of age who are in the hospital, to see if they will also gain weight after taking the <em>B. infantis </em>supplement Bi-26. If the results in our study show that the dietary supplements with this friendly bacterial species of <em>B. infantis</em> improves weight gain among underweight children, then it can potentially be used in poor countries as a dietary supplement in babies who are underweight.</p>\n
      • short_titleCONSTELLATION
      • protocol_noECCT/23/10/06
      • version_no4.0
      • date_of_protocol12-09-2022
      • study_drugBi-26 (strain of Bifidobacterium longum, B. infantis)
      • disease_conditionInfant malnutrition
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_namePlacebo
      • comparator_registeredN/A
      • comparator_countriesN/A
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantFerial Israel
      • declaration_date119-10-2023
      • declaration_principal_investigatorDr Lucas Otieno Tina
      • declaration_date219-10-2023
      • placebo_presentYes
      • study_objectives<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n <strong>Primary Objective</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n To evaluate the change in weight (standardized for age) of infants receiving Bi-26</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n <strong>Key Secondary Objective</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n To evaluate the change in weight of infants receiving Bi-26</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n <strong>Other Secondary Objectives</strong></p>\n<ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \">\n <li style=\"line-height: 20px;\">\n ​​To estimate the treatment response over time associated with Bi-26</li>\n <li style=\"line-height: 20px;\">\n To assess the proportion of infants who achieve a specified change in WAZ from baseline to Day 56</li>\n <li style=\"line-height: 20px;\">\n To assess the proportion of infants who achieve a specified WAZ at Day 56</li>\n <li style=\"line-height: 20px;\">\n To assess the re-hospitalization rate</li>\n <li style=\"line-height: 20px;\">\n To assess the safety of Bi-26 supplementation through End of Study (EoS, Day 90 visit)</li>\n <li style=\"line-height: 20px;\">\n To measure engraftment of B. infantis in participants</li>\n</ul>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n <strong>Exploratory Objectives</strong></div>\n<ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \">\n <li style=\"line-height: 20px;\">\n To describe stool biomarkers in response to Bi-26 supplementation in terms of stool composition (e.g., microbiome, pH)</li>\n <li style=\"line-height: 20px;\">\n To describe the blood biomarkers (e.g., inflammation, metabolomics), in response to Bi-26 supplementation</li>\n</ul>\n<p>\n  </p>\n
      • principal_inclusion_criteria<div style=\"color: rgb(51, 51, 51); font-family: \">\n <strong>Age</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 1. Participant must be between 30 days and 120 days of age (inclusive), at the time of enrollment (study Day 1)</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n <strong>Type of Participant and Disease Characteristics</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 2. Hospitalized for acute non-surgical illness</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 3. Completed acute stabilization phase of treatment, including fluid rehydration and antibiotic course, prior to enrollment (study Day 1)</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n <strong>Weight</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 4. WAZ at enrollment (study Day 1) is less than negative 2 (<-2)</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n <strong>Sex</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 5. Any</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n <strong>Informed consent</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 6. Participant’s parent(s)/legal guardian is capable of giving informed consent which includes agreement to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n <div>\n <strong>Additional requirements</strong></div>\n <div>\n 7. Participant’s parent(s)/legal guardian agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and have no current plans to relocate from the study area for the duration of the study</div>\n <div>\n 8. Participant’s parent(s)/legal guardian has easy access to reliable refrigeration (for storage of investigational product)</div>\n <div>\n 9. Participant receives some feedings from breastmilk and mother intends to continue breastfeeding.</div>\n</div>\n<p>\n  </p>\n
      • principal_exclusion_criteria<div style=\"color: rgb(51, 51, 51); font-family: \">\n 1. Congenital condition (suspected or confirmed) that the investigator considers likely to interfere with feeding or with normal growth and development</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 2. Infant has not been discharged from hospital since birth or has not been at home for at least one week since birth</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 3. Infant hospitalized with septic shock during current hospitalization</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 4. Infant required mechanical ventilation during current hospitalization</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 5. Infant with acute kidney injury on hospital admission</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 6. Infant with severe jaundice and suspected kernicterus</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 7. Infant receiving treatment for suspected or confirmed tuberculosis, or suspected or confirmed HIV infection</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 8. Ongoing infant antibiotic (e.g. as prophylaxis in sickle cell disease) and/or probiotic usage</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 9. Ongoing maternal antibiotic and/or probiotic usage for breast-feeding infants</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 10. Inability of participant’s parent(s)/legal guardian to comply with protocol requirements, as per investigator assessment.</div>\n<p>\n  </p>\n
      • primary_end_points<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n <strong>Primary Endpoints</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n WAZ change from baseline (Day 1) to the Day 56 visit in Bi-26 group</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n <strong>Key Secondary Endpoints</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n Change in weight (in grams) from baseline (Day 1) to the Day 56 visit in the Bi-26 group</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n <strong>Other Secondary Endpoints</strong></p>\n<ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \">\n <li style=\"line-height: 20px;\">\n WAZ change from baseline (Day 1) over time through the Day 90 visit (longitudinal assessment) by duration of dosing</li>\n <li style=\"line-height: 20px;\">\n Proportion of infants with a ≥ 0.3, ≥ 0.4, and ≥ 0.5 change in WAZ from baseline (Day 1) to Day 56 visit</li>\n <li style=\"line-height: 20px;\">\n Proportion of infants who achieve a WAZ > -2 at Day 56 visit</li>\n <li style=\"line-height: 20px;\">\n Number of re-hospitalizations for acute non-surgical illness through the Day 56 visit</li>\n <li style=\"line-height: 20px;\">\n Number of adverse events (AEs) and serious adverse events (SAEs) through Day 90</li>\n <li style=\"line-height: 20px;\">\n Presence of B. infantis in stool on Days 1, 28, 56, and 90</li>\n</ul>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n <strong>Exploratory Endpoints</strong></p>\n<ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \">\n <li style=\"line-height: 20px;\">\n Stool biomarkers on Days 1, 28, and 56</li>\n <li style=\"line-height: 20px;\">\n Blood biomarkers on Days 1 and 28</li>\n</ul>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong><u>Dr Godfrey Otieno</u></strong></p>\n<p>\n KEMRI Kondele Children’s Hospital(KCH) is designed for large clinical trials and has a full clinical laboratory including microbiology capability. The hospital is a KEMRI facility managed in collaboration with Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). The KEMRI KCH study site at JOOTRH is staffed by KEMRI qualified research personnel. The site has a pharmacy, vaccination area, clinical assessment area, data entry area, internal quality control and registration area and space where monitoring can be done. The unit has conducted several clinical trials involving malaria drug, malaria vaccine and sickle cell drugs.</p>\n<p>\n <strong>Dr G Otieno (MBChB) (MMed in Paediatrics and Child Health) </strong>will be the PI on the study. He will provide all the onsite oversight during the study conduct as well s oversee and train the staff at the site.</p>\n<p>\n <strong>Dr B Ogutu (MBChB) (MMed in Paediatrics) and Dr J Orimbo (MBChB) </strong>are the sub-investigators on the study and will assist in various aspects of the study in collaboration with the PI.</p>\n<p>\n <strong>Ruth Wasuna (B Pharm) (MBA) </strong>is the Pharmacist. She will assist with the handling of the investigational product and intepretation of data.</p>\n<p>\n <strong>Ishmael Osoo</strong> is the Study Coordinator oversseing the planning of the study, recruitment, data collection and quality control.</p>\n<p>\n  </p>\n<p>\n <strong><u>Dr Videlis Nduba</u></strong></p>\n<p>\n Site activities at KEMRI/CRDR Nairobi will take place within the clinical research annex located within the KNH complex at the Center for Respiratory Disease Research. This facility has several clinical rooms available for consenting, nursing procedures, clinical exams, and dosing. There are also additional facilities that include 3 bed male and female inpatient ward for admission when required, staff work areas, a monitoring space, a pharmacy, a conference board room, a laboratory, and kitchen for preparing participant meals. Site staff include the principal investigator, 5 medical officers, 3 pharmacists, 1 pharm tech, 8 nurses, 9 lab personnel, 5 quality assurance officers, 10 clinical officers, 3 administrators and 13 community health workers</p>\n<p>\n <strong>Dr V Nduba (MBChB, MPH and PhD in Epidemiology) </strong>has experience with tuberculosis research for the past 13 years where he has led studies examining the prevalence of and incidence of tuberculosis in adolescents and young children, developed local TB culture and immunological capacity including creating a skilled team of individuals with the ability to process and store high quality PBMCs for further TB immunology research. He has conducted two TB vaccine trials, one in infants and the other in adults that included bio banking protocols and extensive immunology sample collection and processing. I also lead a TB drug treatment trial that was looking at a novel new treatment- MPaZ for shortening TB treatment from 6 to 4 months for drug sensitive TB. This research has included developing extensive networks with the TB treatment program, community networks with TB ambassadors and community health.</p>\n<p>\n <strong>Dr Joy Githua (MBChB, MSc), Dr Lucy Kijaro (</strong><strong>MBChB)</strong><strong>, Dr Jacqueline Mirera (MD, MBA-HCM), Dr Lilian Njagi (</strong><strong>MBChB, Dipl in Tropical Medicine and Hygiene, PhD Epidemiology) and </strong><strong>Dr Victor Kariuki Mungai (</strong><strong>MBChB) </strong>are the sub-investigators on the study and will assist in overseeing provision of clinical care to study participants and data collection.</p>\n<p>\n <strong>Julius Kiuri (M Pharm) </strong>is the Pharmacist and will assist with the handling of the investigational product and intepretation of data.</p>\n
      • other_details_explanation<p>\n <span style=\"color: rgb(51, 51, 51); font-family: \">This study focuses on infants in low- and middle-income countries as these are the regions where the burden of disease is greatest as noted in the protocol and the IB. Approximately 90% of underweight children are found in Southeast Asia and Sub-Saharan Africa (</span><a aria-label=\"Link Food Sci Nutr.\" class=\"fui-Link ___1qmgydl f3rmtva f1ewtqcl fyind8e f1k6fduh f1w7gpdv fk6fouc fjoy568 figsok6 f1hu3pq6 f11qmguv f19f4twv f1tyq0we f1g0x7ka fhxju0i f1qch9an f1cnd47f fqv5qza f1vmzxwi f1o700av f13mvf36 f1cmlufx f9n3di6 f1ids18y f1tx3yz7 f1deo86v f1eh06m1 f1iescvh ftqa4ok f2hkw1w fhgqx19 f1olyrje f1p93eir f1h8hb77 f1x7u7e9 f10aw75t fsle3fq\" href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007294/\" rel=\"noreferrer noopener\" style=\"color: rgb(51, 51, 51); text-decoration-line: none; font-family: \" target=\"_blank\" title=\"https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9007294/\">Food Sci Nutr.</a><span style=\"color: rgb(51, 51, 51); font-family: \"> 2022 Apr; 10(4): 1167–1174. </span><a aria-label=\"Link Published online 2022 Jan 18. doi: 10.1002/fsn3.2748\" class=\"fui-Link ___1qmgydl f3rmtva f1ewtqcl fyind8e f1k6fduh f1w7gpdv fk6fouc fjoy568 figsok6 f1hu3pq6 f11qmguv f19f4twv f1tyq0we f1g0x7ka fhxju0i f1qch9an f1cnd47f fqv5qza f1vmzxwi f1o700av f13mvf36 f1cmlufx f9n3di6 f1ids18y f1tx3yz7 f1deo86v f1eh06m1 f1iescvh ftqa4ok f2hkw1w fhgqx19 f1olyrje f1p93eir f1h8hb77 f1x7u7e9 f10aw75t fsle3fq\" href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007294/\" rel=\"noreferrer noopener\" style=\"color: rgb(51, 51, 51); text-decoration-line: none; font-family: \" target=\"_blank\" title=\"https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9007294/\">Published online 2022 Jan 18. doi: 10.1002/fsn3.2748</a><span style=\"color: rgb(51, 51, 51); font-family: \">). Thus, countries in these regions were selected for participation in this study, including Kenya, as there is an unmet medical need for management of underweight infants in those regions.</span></p>\n<p>\n  </p>\n
      • other_details_regulatory_notapproved<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n Tanzania - 30 Dec 2022</p>\n<p>\n  </p>\n
      • other_details_regulatory_approved<p>\n <span style=\"color: rgb(51, 51, 51); font-family: \">Pakistan - approved 13 April 2023</span></p>\n<p>\n <span style=\"color: rgb(51, 51, 51); font-family: \">Bangladesh - issued letter on 09 Aug 2023 informing that th</span>e probiotic was approved for commercialization/use in the country.</p>\n<p>\n <font color=\"#333333\">Pakistan - 7 sites</font></p>\n<p>\n <span style=\"color: rgb(51, 51, 51);\">Bangladesh - 1 site</span></p>\n<p>\n  </p>\n<p>\n <span style=\"color: rgb(51, 51, 51);\">Tanzania will have 3 sites once approved</span></p>\n
      • other_details_regulatory_rejected<p>\n <span style=\"color: rgb(51, 51, 51); font-family: \">Not applicable</span></p>\n
      • other_details_regulatory_halted<p>\n <span style=\"color: rgb(51, 51, 51); font-family: \">Not applicable</span></p>\n
      • estimated_durationThe study duration for each participant is approximately 3 months.
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorpotato maltodextrin
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites8
      • multi_country_listKenya, Tanzania, Pakistan and Bangladesh
      • data_monitoring_committeeYes
      • total_enrolment_per_siteMinimum per site = 5, maximum per site = 30
      • total_participants_worldwide396
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyMalnourished infants
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Lucas
      • investigator1_middle_nameOtieno
      • investigator1_family_nameTina
      • investigator1_qualificationMBChB, MPH DLSHTM
      • investigator1_professional_addressVictoria Biomedical Research Institute, Kisumu County Referral Hospital Off Ang\'awa Road, P.O. Box 7180, Postal Code 40100, Kisumu, Kenya
      • investigator1_telephone+254708358451
      • investigator1_emailltina@vibriafrica.org
      • organisations_transferred_Yes
      • number_participants160
      • notification<p>\n The study has already been reviewed and approved by KPPB on 31 July 2023, which included the site of Dr Lucas Tina. This application is the submission of the additional sites of Dr G Otieno and Dr V Nduba.</p>\n
      • approval_date19-12-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted19-10-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApproved by reviewers since its an additional site to an already approved protocol.
      • final_report
      • implication_results
      • quantity_imported
      • quantity_dispensed
      • quantity_destroyed
      • quantity_exported
      • balance_site
      • final_date0000-00-00
      • modified2025-04-24 17:53:11
      • created2023-09-26 11:56:00
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id973
        • application_id1330
        • given_nameDr Godfrey
        • middle_nameAllan
        • family_nameOtieno
        • qualificationMBChB, MMed (Paed) (Nrb)
        • professional_addressKEMRI-Kondele Children’s Hospital, within Jaramogi Oginga Odinga Teaching and Referral Hospital, along Kisumu - Kakamega Road, Kisumu, Kenya
        • telephone+254 733 893481
        • emailgotieno@gmail.com
        • created2023-09-26 11:58:11
        • modified2023-10-19 12:22:28
      • 1(array)
        • id975
        • application_id1330
        • given_nameDr Videlis
        • middle_name
        • family_nameNduba
        • qualificationMBChB, MPH, PhD
        • professional_addressKEMRI CRDR Clinical Research Annex, On Kenyatta National Hospital Grounds, Off hospital Road, Behind Government Chemist P.O BOX 47855-00100
        • telephone+254 724522474
        • emailvnduba@kemri.org
        • created2023-09-26 12:31:09
        • modified2023-10-19 12:22:28
    • SiteDetail(array)
      • 0(array)
        • id1600
        • application_id1330
        • county_id42
        • site_nameKEMRI-Kondele Children’s Hospital
        • physical_addresswithin Jaramogi Oginga Odinga Teaching and Referral Hospital, along Kisumu - Kakamega Road, Kisumu, Kenya
        • contact_details+254 733 893481
        • contact_personDr Godfrey Otieno
        • site_capacity(null)
        • misc(null)
        • created2023-09-26 11:58:11
        • modified2023-10-19 12:22:28
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id1611
        • application_id1330
        • county_id47
        • site_nameKEMRI CRDR Clinical Research Annex
        • physical_addressOn Kenyatta National Hospital Grounds, Off hospital Road, Behind Government Chemist P.O BOX 47855-00100
        • contact_details254 724 522474
        • contact_personDr Videlus Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-10-12 20:16:18
        • modified2023-10-19 12:22:28
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id697
        • application_id1330
        • sponsorBill & Melinda Gates Medical Research Institute
        • sponsor_typeResearch Institution
        • contact_personJanie Parrino
        • addressOne Kendall Square Building 600,Cambridge, Massachusetts, 02139, United States
        • telephone_number+12155397606
        • fax_number
        • cell_numberN/A
        • email_addressjanie.parrino@gatesmri.org
        • created2023-09-26 11:58:11
        • modified2023-10-19 12:22:28
  • 4(array)
    • Application(array)
      • id1331
      • user_id263
      • trial_status_id4
      • abstract_of_study<div>\n Bifidobacteria are gram-positive, heterofermentative, anaerobic bacteria that colonize the newborn gut within the first days and weeks of life. They are often the most abundant bacterial genus in a breast-fed infant’s intestinal flora. B. infantis metabolizes Human milk oligosaccharides (HMOs) and produces short chain fatty acids (SCFA) that are thought to play an important role in nutrition and immune development, stimulating anti-inflammatory and inhibiting pro-inflammatory responses [Halloran 2019; Henrick 2021].</div>\n<div>\n  </div>\n<div>\n B. infantis Bi-26 strain is a nutritional probiotic intervention that will be evaluated in this trial for its ability to improve weight gain and health outcomes of underweight infants with WAZ <-2 who have been hospitalized with acute illness.</div>\n<div>\n  </div>\n<div>\n Clinical study data in the United States (US) have shown that B. infantis strain EVC001 colonizes the gut and is associated with significant changes to fecal microbiome composition in healthy breast-fed infants [Frese 2017; Henrick 2019]. Supplementation of B. infantis EVC001 has been associated with a reduction in pro-inflammatory cytokines [Henrick 2019]. Similar observations have been reported for preterm infants given B. infantis EVC001 [Nguyen 2021].</div>\n<div>\n  </div>\n<div>\n In a pilot trial evaluating B. infantis EVC001 supplementation in Bangladesh in hospitalized 2-to 6-month-old infants with SAM, i.e., weight-for-length z score [WLZ] <-3, researchers observed that daily supplementation with B. infantis for 4 weeks was associated with B. infantis colonization and an increase in WAZ [Barratt 2022].</div>\n<div>\n  </div>\n<div>\n A number of B. infantis strains, including Bi-26, have been designated as generally recognized as safe (GRAS) based on review by a panel of independent experts in the field. Furthermore, the US Food and Drug Administration (FDA) did not have questions about the GRAS determination of Bi-26 (GRN 985). In the US, the GRAS determination and the FDA no question letter allow the use of Bi-26 under its intended conditions of use (healthy term infants) in infant formula. The strain bearing the GRAS designation can also be used in dietary supplements, including those for infants.</div>\n<p>\n In low-income countries, B. infantis strain Bi-26, evaluated in this study, could potentially be used as a dietary supplement in underweight infants if the safety and efficacy findings of the previous pilot study are confirmed.</p>\n<p>\n  </p>\n
      • study_title<p>\n A Phase 3, randomized, double-blind, placebo-controlled study to evaluate the effect of Bi-26 (strain of Bifidobacterium longum, B. infantis) supplementation versus placebo on weight gain in underweight infants</p>\n
      • laymans_summary<p>\n Poor countries bear a greater burden of children who are born with a weight that is less than it should be for their age. Poor health in the digestive system (gut) can be caused by a poor balance of good bacteria that are thought to play a role in how nutrients are absorbed in the intestines. Good bacteria in a baby’s gut are important in helping the baby grow, develop normally, and be healthier. One of the bacteria, called <em>B. infantis</em>, that is normally found in babies’ guts makes it easier for the baby to digest their mother’s milk and help keep the baby healthy. Babies who have a weight that is less than it should be for their age have less of the <em>B. infantis</em> bacteria, compared to healthy babies. This may cause poor absorption of these nutrients and can lead to babies not being able to gain weight, leading to them becoming underweight and failing to thrive. Providing a dietary supplement with a specific strain of the bacteria known as EVC001 has been shown to boost the friendly bacteria living in the gut and cause significant changes in the composition of the friendly bacteria and its environment in the gut especially in healthy babies who are breastfed. </p>\n<p>\n A small study in Bangladesh tested this strain among babies who were aged between 2 and 6 months and had been admitted to hospital, who were also suffering from severe acute malnutrition. They were given the friendly <em>B. infantis</em> bacteria species as a dietary supplement daily for a period of four weeks. It was found out that this supplementation boosted the friendly bacteria and resulted in the children gaining weight and improving their nutritional weight-for-age Z score (WAZ). We want to study underweight babies who are between 1 and 4 months of age who are in the hospital, to see if they will also gain weight after taking the <em>B. infantis </em>supplement Bi-26. If the results in our study show that the dietary supplements with this friendly bacterial species of <em>B. infantis</em> improves weight gain among underweight children, then it can potentially be used in poor countries as a dietary supplement in babies who are underweight.</p>\n<p>\n  </p>\n
      • short_titleCONSTELLATION
      • protocol_noECCT/23/12/03
      • version_no4.0
      • date_of_protocol12-09-2022
      • study_drugBi-26 (strain of Bifidobacterium longum, B. infantis)
      • disease_conditionInfant malnutrition
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_namePlacebo
      • comparator_registeredN/A
      • comparator_countriesN/A
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantFerial Israel
      • declaration_date114-12-2023
      • declaration_principal_investigatorDr Lucas Otieno Tina
      • declaration_date214-12-2023
      • placebo_presentYes
      • study_objectives<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n <strong>Primary Objective</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n To evaluate the change in weight (standardized for age) of infants receiving Bi-26</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n <strong>Key Secondary Objective</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n To evaluate the change in weight of infants receiving Bi-26</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n <strong>Other Secondary Objectives</strong></p>\n<ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \">\n <li style=\"line-height: 20px;\">\n ​​To estimate the treatment response over time associated with Bi-26</li>\n <li style=\"line-height: 20px;\">\n To assess the proportion of infants who achieve a specified change in WAZ from baseline to Day 56</li>\n <li style=\"line-height: 20px;\">\n To assess the proportion of infants who achieve a specified WAZ at Day 56</li>\n <li style=\"line-height: 20px;\">\n To assess the re-hospitalization rate</li>\n <li style=\"line-height: 20px;\">\n To assess the safety of Bi-26 supplementation through End of Study (EoS, Day 90 visit)</li>\n <li style=\"line-height: 20px;\">\n To measure engraftment of B. infantis in participants</li>\n</ul>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n <strong>Exploratory Objectives</strong></div>\n<ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \">\n <li style=\"line-height: 20px;\">\n To describe stool biomarkers in response to Bi-26 supplementation in terms of stool composition (e.g., microbiome, pH)</li>\n <li style=\"line-height: 20px;\">\n To describe the blood biomarkers (e.g., inflammation, metabolomics), in response to Bi-26 supplementation</li>\n</ul>\n<p>\n  </p>\n
      • principal_inclusion_criteria<div style=\"color: rgb(51, 51, 51); font-family: \">\n <strong>Age</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 1. Participant must be between 30 days and 120 days of age (inclusive), at the time of enrollment (study Day 1)</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n <strong>Type of Participant and Disease Characteristics</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 2. Hospitalized for acute non-surgical illness</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 3. Completed acute stabilization phase of treatment, including fluid rehydration and antibiotic course, prior to enrollment (study Day 1)</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n <strong>Weight</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 4. WAZ at enrollment (study Day 1) is less than negative 2 (<-2)</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n <strong>Sex</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 5. Any</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n <strong>Informed consent</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 6. Participant’s parent(s)/legal guardian is capable of giving informed consent which includes agreement to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n <div>\n <strong>Additional requirements</strong></div>\n <div>\n 7. Participant’s parent(s)/legal guardian agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and have no current plans to relocate from the study area for the duration of the study</div>\n <div>\n 8. Participant’s parent(s)/legal guardian has easy access to reliable refrigeration (for storage of investigational product)</div>\n <div>\n 9. Participant receives some feedings from breastmilk and mother intends to continue breastfeeding.</div>\n</div>\n<p>\n  </p>\n
      • principal_exclusion_criteria<div style=\"color: rgb(51, 51, 51); font-family: \">\n 1. Congenital condition (suspected or confirmed) that the investigator considers likely to interfere with feeding or with normal growth and development</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 2. Infant has not been discharged from hospital since birth or has not been at home for at least one week since birth</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 3. Infant hospitalized with septic shock during current hospitalization</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 4. Infant required mechanical ventilation during current hospitalization</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 5. Infant with acute kidney injury on hospital admission</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 6. Infant with severe jaundice and suspected kernicterus</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 7. Infant receiving treatment for suspected or confirmed tuberculosis, or suspected or confirmed HIV infection</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 8. Ongoing infant antibiotic (e.g. as prophylaxis in sickle cell disease) and/or probiotic usage</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 9. Ongoing maternal antibiotic and/or probiotic usage for breast-feeding infants</div>\n<div style=\"color: rgb(51, 51, 51); font-family: \">\n 10. Inability of participant’s parent(s)/legal guardian to comply with protocol requirements, as per investigator assessment.</div>\n<p>\n  </p>\n
      • primary_end_points<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n <strong>Primary Endpoints</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n WAZ change from baseline (Day 1) to the Day 56 visit in Bi-26 group</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n <strong>Key Secondary Endpoints</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n Change in weight (in grams) from baseline (Day 1) to the Day 56 visit in the Bi-26 group</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n <strong>Other Secondary Endpoints</strong></p>\n<ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \">\n <li style=\"line-height: 20px;\">\n WAZ change from baseline (Day 1) over time through the Day 90 visit (longitudinal assessment) by duration of dosing</li>\n <li style=\"line-height: 20px;\">\n Proportion of infants with a ≥ 0.3, ≥ 0.4, and ≥ 0.5 change in WAZ from baseline (Day 1) to Day 56 visit</li>\n <li style=\"line-height: 20px;\">\n Proportion of infants who achieve a WAZ > -2 at Day 56 visit</li>\n <li style=\"line-height: 20px;\">\n Number of re-hospitalizations for acute non-surgical illness through the Day 56 visit</li>\n <li style=\"line-height: 20px;\">\n Number of adverse events (AEs) and serious adverse events (SAEs) through Day 90</li>\n <li style=\"line-height: 20px;\">\n Presence of B. infantis in stool on Days 1, 28, 56, and 90</li>\n</ul>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n <strong>Exploratory Endpoints</strong></p>\n<ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \">\n <li style=\"line-height: 20px;\">\n Stool biomarkers on Days 1, 28, and 56</li>\n <li style=\"line-height: 20px;\">\n Blood biomarkers on Days 1 and 28</li>\n</ul>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n <u><strong>Dr Benson Singa</strong></u></div>\n<div>\n The KEMRI/UW team will operate as part of the larger global study and will be responsible for study operations at Migori County Referral Hospital. The hospital serves a catchment area with significant burden of under five malnutrition (10% prevalence [data from hospital records]) therefore, the infant population here may stand to benefit from the novel intervention. KEMRI/UW team has implemented multiple large-scale clinical trials and research over the years and the study team has since developed strong partnerships with the leadership and clinical staff in the hospital.</div>\n<div>\n  </div>\n<div>\n <strong>Dr B Singa (MBChB) (MPH)</strong> is a research scientist at the Kenya Medical Research Institute, Centre for Clinical Research. He has been a close collaborator on several studies of helminth, malaria, STI and HIV co-infection over the past years including programmatic evaluation. Dr Singa has served as a principal investigator, a co-investigator and a medical coordinator on these studies. Benson’s background interest is in Public Health especially Sexual Reproductive Adolescent and Child Health.</div>\n<div>\n These interests encompass both preventive, promotive and curative services. Additionally, Dr Singa has interests in tropical medicine especially immune modulation and interaction between tropical diseases and HIV with having been involved in studies on current emerging issues and progress in this field especially given the continuing concern of barely contained tropical diseases and HIV infection around the globe. Currently, Dr Singa is involved in evaluating ongoing programs especially PMTCT program and HIV in children and adolescents in a bid to improve the preventive programs being implemented in the healthcare set up. Additionally, Dr Singa has been involved in multi-Country, multi-site research studies in the area of Diarrhoea and Childhood Acute Illness and Nutrition.</div>\n<div>\n  </div>\n<div>\n <strong>Judd Walson, MD, MPH </strong>is a Professor in the Department of Global Health, Medicine (Allergy and Infectious Disease), Pediatrics and Epidemiology (Adjunct) at the University of Washington. Dr. Walson has an extensive history of conducting large clinical trials in Africa and Asia, funded by NIH, CDC, private foundations and industry. His work focuses on</div>\n<div>\n developing interventions to reduce childhood morbidity and mortality in low-income settings, particularly at the intersection of infectious disease and malnutrition and other poverty related vulnerabilities. Dr. Walson is a co-Principal Investigator of the Childhood Acute Illness and Nutrition Network, a nine-site, six country project which aims to identify and test interventions to improve child survival among highly vulnerable infants in Africa and Asia. He is also the Principal Investigator of the DeWorm3 Project, a large multi-country cluster randomized trial designed to demonstrate the feasibility of interrupting the transmission of soil-transmitted helminths. He has extensive experience in the design and implementation of observational research and multi-site clinical trials and he works closely with numerous government and non-governmental organizations. He has strong</div>\n<div>\n relationships with stakeholders in Benin, Burkina Faso, Kenya, Malawi, Uganda, Tanzania, Mali, India, Pakistan, Nepal and Bangladesh. Dr. Walson has mentored over 60 post-doctoral, doctoral and master levels trainees both in the US and overseas.</div>\n<div>\n  </div>\n<div>\n <strong>Dr Kirkby Daniel Tickell (BSc in Neuroscience and Mental Health, MBBS, MPH in Epidemiology and PHc in Epidemiology)</strong></div>\n<div>\n Both Dr Kirkby and Dr Walson are the sub-investigators on the study and will assist in various aspects of trial including patient oversight and data collection.</div>\n<div>\n  </div>\n<div>\n <strong>Lucia Keter (M Pharm and B Pharm)</strong> is the Pharmacist. She will assist with the handling of the investigational product and intepretation of data.</div>\n<div>\n  </div>\n<div>\n <strong>Beatrice Olack </strong>is the Study Coordinator oversseing the planning of the study, recruitment, data collection and quality control.</div>\n<div>\n  </div>\n<div>\n <strong>Churchill Nyanda and Chrisantus Oduol </strong>are Clinical Officers and will assist with overseeing patient care, collecting patient study information and clinical assessments.</div>\n<div>\n  </div>\n<div>\n <strong>Charles Mutinda </strong>is the Laboratory Manager overseeing the handling of patient samples and shipments.</div>\n<div>\n  </div>\n<div>\n <strong>Eric Ochola </strong>is the Data Manager who will oversee the captureing of patient data in the EDC systems.</div>\n
      • other_details_explanation<p>\n <span style=\"color: rgb(51, 51, 51); font-family: \">This study focuses on infants in low- and middle-income countries as these are the regions where the burden of disease is greatest as noted in the protocol and the IB. Approximately 90% of underweight children are found in Southeast Asia and Sub-Saharan Africa (</span><a aria-label=\"Link Food Sci Nutr.\" class=\"fui-Link ___1qmgydl f3rmtva f1ewtqcl fyind8e f1k6fduh f1w7gpdv fk6fouc fjoy568 figsok6 f1hu3pq6 f11qmguv f19f4twv f1tyq0we f1g0x7ka fhxju0i f1qch9an f1cnd47f fqv5qza f1vmzxwi f1o700av f13mvf36 f1cmlufx f9n3di6 f1ids18y f1tx3yz7 f1deo86v f1eh06m1 f1iescvh ftqa4ok f2hkw1w fhgqx19 f1olyrje f1p93eir f1h8hb77 f1x7u7e9 f10aw75t fsle3fq\" href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007294/\" rel=\"noreferrer noopener\" style=\"color: rgb(51, 51, 51); text-decoration-line: none; font-family: \" target=\"_blank\" title=\"https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9007294/\">Food Sci Nutr.</a><span style=\"color: rgb(51, 51, 51); font-family: \"> 2022 Apr; 10(4): 1167–1174. </span><a aria-label=\"Link Published online 2022 Jan 18. doi: 10.1002/fsn3.2748\" class=\"fui-Link ___1qmgydl f3rmtva f1ewtqcl fyind8e f1k6fduh f1w7gpdv fk6fouc fjoy568 figsok6 f1hu3pq6 f11qmguv f19f4twv f1tyq0we f1g0x7ka fhxju0i f1qch9an f1cnd47f fqv5qza f1vmzxwi f1o700av f13mvf36 f1cmlufx f9n3di6 f1ids18y f1tx3yz7 f1deo86v f1eh06m1 f1iescvh ftqa4ok f2hkw1w fhgqx19 f1olyrje f1p93eir f1h8hb77 f1x7u7e9 f10aw75t fsle3fq\" href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007294/\" rel=\"noreferrer noopener\" style=\"color: rgb(51, 51, 51); text-decoration-line: none; font-family: \" target=\"_blank\" title=\"https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9007294/\">Published online 2022 Jan 18. doi: 10.1002/fsn3.2748</a><span style=\"color: rgb(51, 51, 51); font-family: \">). Thus, countries in these regions were selected for participation in this study, including Kenya, as there is an unmet medical need for management of underweight infants in those regions.</span></p>\n
      • other_details_regulatory_notapproved<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \">\n Tanzania - 30 Dec 2022</p>\n<p>\n  </p>\n
      • other_details_regulatory_approved<div>\n Pakistan - approved 13 April 2023</div>\n<div>\n Bangladesh - issued letter on 09 Aug 2023 informing that the probiotic was approved for commercialization/use in the country.</div>\n<div>\n  </div>\n<div>\n Pakistan - 7 sites</div>\n<div>\n Bangladesh - 1 site</div>\n<div>\n  </div>\n<div>\n Tanzania will have 3 sites once approved.</div>\n
      • other_details_regulatory_rejected<p>\n <span style=\"color: rgb(51, 51, 51); font-family: \">Not applicable</span></p>\n
      • other_details_regulatory_halted<p>\n <span style=\"color: rgb(51, 51, 51); font-family: \">Not applicable</span></p>\n
      • estimated_durationThe study duration for each participant is approximately 3 months.
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorpotato maltodextrin
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites8
      • multi_country_listKenya, Tanzania, Pakistan and Bangladesh
      • data_monitoring_committeeYes
      • total_enrolment_per_siteMinimum per site = 5, maximum per site = 30
      • total_participants_worldwide396
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyMalnourished infants
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Lucas
      • investigator1_middle_nameOtieno
      • investigator1_family_nameTina
      • investigator1_qualificationMBChB, MPH DLSHTM
      • investigator1_professional_addressVictoria Biomedical Research Institute, Kisumu County Referral Hospital Off Ang\'awa Road, P.O. Box 7180, Postal Code 40100, Kisumu, Kenya
      • investigator1_telephone+254708358451
      • investigator1_emailltina@vibriafrica.org
      • organisations_transferred_Yes
      • number_participants160
      • notification<p>\n The study has already been reviewed and approved by KPPB on 31 July 2023. This included the site of Dr Lucas Tina. This application is the submission of an additional site of Dr Benson Singa.</p>\n
      • approval_date07-05-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted14-12-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed adequately.
      • final_report
      • implication_results
      • quantity_imported0
      • quantity_dispensed0
      • quantity_destroyed0
      • quantity_exported0
      • balance_site0
      • final_date0000-00-00
      • modified2025-04-24 19:05:46
      • created2023-09-26 12:34:34
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id976
        • application_id1331
        • given_nameDr Benson
        • middle_nameOchieng
        • family_nameSinga
        • qualificationMBChB, Post Graduate Dipl in Trop Med, MPH
        • professional_addressMigori County Referral Hospital, C/O KEMRI/University of Washington, P.O. Box 202-40400 Suna Migori, Kenya
        • telephone+254 725234844
        • emailsingabo2008@gmail.com
        • created2023-09-26 12:54:30
        • modified2023-12-14 18:41:46
    • SiteDetail(array)
      • 0(array)
        • id1601
        • application_id1331
        • county_id44
        • site_nameMigori County Referral Hospital
        • physical_addressC/O KEMRI/University of Washington, P.O. Box 202-40400 Suna Migori, Kenya
        • contact_details+254 725234844
        • contact_personDr Benson Singa
        • site_capacity(null)
        • misc(null)
        • created2023-09-26 12:54:30
        • modified2023-12-14 18:41:46
        • County(array)
          • id44
          • county_nameMigori
          • created2012-06-15 10:27:16
          • modified2012-06-15 10:27:16
    • Sponsor(array)
      • 0(array)
        • id698
        • application_id1331
        • sponsorBill & Melinda Gates Medical Research Institute
        • sponsor_typeResearch Institution
        • contact_personJanie Parrino
        • addressOne Kendall Square Building 600,Cambridge, Massachusetts, 02139, United States
        • telephone_number+12155397606
        • fax_number
        • cell_numberN/A
        • email_addressjanie.parrino@gatesmri.org
        • created2023-09-26 12:54:30
        • modified2023-12-14 18:41:46
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(array)
    • trial_therapeutic_confirmatory1
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
  • Aco(empty)
  • Application(empty)
  • User(empty)
  • TrialStatus(empty)
  • InvestigatorContact(empty)
  • Sponsor(empty)
  • SiteDetail(empty)
  • County(empty)
• Loaded Helpers(array)
  • 0Html
  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
  • 7DebugTimer
  • 8Toolbar
  • 9HtmlToolbar

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

• 0/var/www/html/ctr/app/Plugin/Media/Lib/mm/src
• 1/var/www/html/ctr/lib
• 3/usr/share/php
• 4-> /var/www/html/ctr/lib/Cake/

Included Files

• core(array)
  • Behavior(array)
    • 0CORE/Model/Behavior/TreeBehavior.php
    • 1CORE/Model/Behavior/ContainableBehavior.php
    • 2CORE/Model/Behavior/AclBehavior.php
  • Cache(array)
    • 0CORE/Cache/Cache.php
    • 1CORE/Cache/Engine/FileEngine.php
    • 2CORE/Cache/CacheEngine.php
  • Component(array)
    • 0CORE/Controller/Component/AclComponent.php
    • 1CORE/Controller/Component/Acl/DbAcl.php
    • 2CORE/Controller/Component/Acl/AclInterface.php
    • 3CORE/Controller/Component/AuthComponent.php
    • 4CORE/Controller/Component/RequestHandlerComponent.php
    • 5CORE/Controller/Component/SessionComponent.php
    • 6CORE/Controller/Component/PaginatorComponent.php
  • Config(array)
    • 0CORE/Config/routes.php
    • 1CORE/Config/config.php
  • Controller(array)
    • 0CORE/Controller/Controller.php
    • 1CORE/Controller/ComponentCollection.php
    • 2CORE/Controller/Component.php
  • Datasource(array)
    • 0CORE/Model/Datasource/CakeSession.php
    • 1CORE/Model/Datasource/Database/Mysql.php
    • 2CORE/Model/Datasource/DboSource.php
    • 3CORE/Model/Datasource/DataSource.php
  • Error(array)
    • 0CORE/Error/exceptions.php
    • 1CORE/Error/ErrorHandler.php
  • I18n(array)
    • 0CORE/I18n/I18n.php
    • 1CORE/I18n/L10n.php
  • Log(array)
    • 0CORE/Log/CakeLog.php
    • 1CORE/Log/LogEngineCollection.php
    • 2CORE/Log/Engine/FileLog.php
    • 3CORE/Log/Engine/BaseLog.php
    • 4CORE/Log/CakeLogInterface.php
  • Model(array)
    • 0CORE/Model/ConnectionManager.php
    • 1CORE/Model/Permission.php
    • 2CORE/Model/Model.php
    • 3CORE/Model/BehaviorCollection.php
    • 4CORE/Model/Aro.php
    • 5CORE/Model/AclNode.php
    • 6CORE/Model/Aco.php
    • 7CORE/Model/ModelBehavior.php
  • Network(array)
    • 0CORE/Network/CakeRequest.php
    • 1CORE/Network/CakeResponse.php
  • Other(array)
    • 0CORE/bootstrap.php
    • 1CORE/basics.php
    • 2CORE/Core/App.php
    • 3CORE/Core/Configure.php
    • 4CORE/Core/CakePlugin.php
    • 5CORE/Event/CakeEventListener.php
    • 6CORE/Event/CakeEvent.php
    • 7CORE/Event/CakeEventManager.php
    • 8CORE/Core/Object.php
  • Routing(array)
    • 0CORE/Routing/Dispatcher.php
    • 1CORE/Routing/Filter/AssetDispatcher.php
    • 2CORE/Routing/DispatcherFilter.php
    • 3CORE/Routing/Filter/CacheDispatcher.php
    • 4CORE/Routing/Router.php
    • 5CORE/Routing/Route/CakeRoute.php
    • 6CORE/Routing/Route/PluginShortRoute.php
  • Utility(array)
    • 0CORE/Utility/Hash.php
    • 1CORE/Utility/Inflector.php
    • 2CORE/Utility/ObjectCollection.php
    • 3CORE/Utility/Debugger.php
    • 4CORE/Utility/String.php
    • 5CORE/Utility/ClassRegistry.php
    • 6CORE/Utility/Set.php
    • 7CORE/Utility/Sanitize.php
  • View(array)
    • 0CORE/View/HelperCollection.php
• app(array)
  • Behavior(array)
    • 0APP/Model/Behavior/SoftDeleteBehavior.php
  • Config(array)
    • 0APP/Config/core.php
    • 1APP/Config/bootstrap.php
    • 2APP/Config/routes.php
    • 3APP/Config/database.php
  • Controller(array)
    • 0APP/Controller/ApplicationsController.php
    • 1APP/Controller/AppController.php
  • Model(array)
    • 0APP/Model/AppModel.php
    • 1APP/Model/Application.php
    • 2APP/Model/User.php
    • 3APP/Model/TrialStatus.php
    • 4APP/Model/InvestigatorContact.php
    • 5APP/Model/Sponsor.php
    • 6APP/Model/SiteDetail.php
    • 7APP/Model/County.php
  • Other(array)
    • 0APP/webroot/index.php
• plugins(array)
  • CakePdf(array)
    • Config(array)
      • 0CakePdf/Config/bootstrap.php
      • 1CakePdf/Config/routes.php
  • CakeResque(array)
    • Config(array)
      • 0CakeResque/Config/bootstrap.php
    • Plugin(array)
      • 0CakeResque/Lib/CakeResque.php
      • 1CakeResque/vendor/kamisama/php-resque-ex/lib/Resque.php
      • 2CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Event.php
      • 3CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Exception.php
  • DebugKit(array)
    • Component(array)
      • 0DebugKit/Controller/Component/ToolbarComponent.php
    • Plugin(array)
      • 0DebugKit/Lib/DebugMemory.php
      • 1DebugKit/Lib/Panel/HistoryPanel.php
      • 2DebugKit/Lib/DebugPanel.php
      • 3DebugKit/Lib/Panel/SessionPanel.php
      • 4DebugKit/Lib/Panel/RequestPanel.php
      • 5DebugKit/Lib/Panel/SqlLogPanel.php
      • 6DebugKit/Lib/Panel/TimerPanel.php
      • 7DebugKit/Lib/Panel/LogPanel.php
      • 8DebugKit/Lib/Log/Engine/DebugKitLog.php
      • 9DebugKit/Lib/Panel/VariablesPanel.php
      • 10DebugKit/Lib/Panel/EnvironmentPanel.php
      • 11DebugKit/Lib/Panel/IncludePanel.php
      • 12DebugKit/Lib/DebugTimer.php
  • Media(array)
    • Config(array)
      • 0Media/Config/bootstrap.php
    • Plugin(array)
      • 0Media/Lib/mm/src/Mime/Type.php
      • 1Media/Lib/mm/src/Mime/Type/Magic/Adapter/Fileinfo.php
      • 2Media/Lib/mm/src/Mime/Type/Magic/Adapter.php
      • 3Media/Lib/mm/src/Mime/Type/Glob/Adapter/Memory.php
      • 4Media/Lib/mm/src/Mime/Type/Glob/Adapter.php
      • 5Media/Lib/mm/src/Media/Process.php
      • 6Media/Lib/mm/src/Media/Info.php
  • Search(array)
    • Component(array)
      • 0Search/Controller/Component/PrgComponent.php
    • Behavior(array)
      • 0Search/Model/Behavior/SearchableBehavior.php
  • Shim(array)
    • Config(array)
      • 0Shim/Config/bootstrap.php
  • Tools(array)
    • Config(array)
      • 0Tools/Config/bootstrap.php