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      • id984
      • user_id71
      • trial_status_id5
      • abstract_of_study<p>\n This Phase III study is a global multicentre, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy, safety, and immunogenicity of the recombinant COVID-19 vaccine (Sf9 cells) in 40,000 participants aged 18 years and older who do not have known history of SARS-CoV-2 infection but whose locations or circumstances put them at appreciable risk of acquiring COVID-19 or SARS-CoV-2 infection. Globally, there will be three cohorts in the study: the efficacy-safety cohort, the efficacy-extended safety cohort, and the efficacy-extended safety-immunogenicity cohort. The efficacy will be evaluated in all vaccinated participants, including population in the efficacy-safety cohort, the efficacy-extended safety cohort, and the efficacy-extended safety-immunogenicity cohort. All vaccinated participants will also be followed up to monitor incidence of SAEs, MAAEs and AESIs. The reactogenicity of the vaccine will be evaluated in the efficacy-extended safety cohort and the efficacy-extended safety-immunogenicity cohort. KAVI-Institute for Clinical Research will recruit 400 clinical trial participants. All the participants will be in the efficacy-extended safety-immunogenicity cohort, and will receive three doses of either the vaccine or placebo on Day 0, Day 21, Day 42 in a ratio of 1:1. This cohort will undergo additional visits to collect immunogenicity data associated with receiving the recombinant COVID-19 vaccine (Sf9 cells) and to analyse the infection status. There will be at least seven planned site visits on Day -7-Day 0, Day 0, Day 21, Day 42, 28 days, 6 months and 12 months after completion of 3 vaccination doses. The first site visit will be the screening visit (Day -7-Day 0), and will be held within 7 days prior to the enrolment visit (Day 0). During the screening visit, study staff will obtain written informed consent from the participants, record medical history, review inclusion and exclusion criteria, test HIV antibody, test SARS-CoV-2 RT-PCR of NP or OP swab, and do urine pregnancy test in women of child-bearing potential etc. At enrolment visit (Day 0), blood sample will be collected from the participants to establish baseline immunogenicity levels. Participants will then be randomized to either the placebo or study vaccine group and receive their vaccination. The participant and investigators will remain blinded to the assigned group. Participants are required to stay at the study site for at least 30 minutes after vaccination to monitor for any vaccine-related AE. All participants will be contacted weekly to be reminded to report any signs or symptoms of COVID-19 to study staff. Participants will be contacted by the site weekly by phone or short text messaging (sms) to answer questions about whether they have SAEs, MAAEs or AESIs. The reporting and monitoring of any participant’s illness are consistent with meeting the primary efficacy objective. If a participant becomes ill, they will be asked to immediately proceed to the site designated by their local study team where they will be assessed and treated as deemed appropriate. Participants will be given an e-diary or paper diary card to record solicited AEs within 7 days after each vaccination dose and to record unsolicited AEs within 21 days after the first dose and the second dose, and within 28 days after the third vaccination dose. Study staff will review the completed e-diary or diary card of participants in these cohorts at their next site visit. Data collected from e-diaries and diary cards will be uploaded into the electronic data capture (EDC). Site visits will be conducted on 28 days, 6 months and 12 months after completion of 3 vaccination doses during which blood sample will also be collected . Participants should contact the investigator immediately if they notice any signs or symptoms related to COVID-19.If a participant in these three cohorts demonstrates signs or symptoms of COVID-19, an unplanned site visit may occur for evaluation and possible treatment. After an electronic follow-up visit, if for any reason, the investigator would like to conduct a site visit, they may do this at their discretion.</p>\n
      • study_title<p>\n A global multicenter, randomized, double-blind, placebo-controlled, phase III clinical trial to evaluate the efficacy, safety, and immunogenicity of recombinant COVID-19 vaccine (Sf9 cells), for the prevention of COVID-19 in adults aged 18 years and older</p>\n
      • laymans_summary<p>\n This study is about a vaccine for COVID-19. COVID-19 is a respiratory infection that has spread around the world. The infection is caused by a virus called SARS-CoV-2. From now on, we will call it “the COVID-19 virus”. People can catch the virus by breathing the air near people who are infected. They may also get the virus by touching something that has the virus on it and then touching their eyes, nose, or mouth. Keeping distance from others, wearing a mask, and frequent hand washing are important ways to prevent infection. COVID-19 infection causes a wide range of health issues. Some people show no symptoms, while others experience serious medical problems and need a ventilator to help them breathe. Many people have died from the virus. In the end, the best protection against COVID-19 will be an effective vaccine. That is what this research study is about. Everyone’s body has an immune system- special cells that act together to fight viruses and other invaders. The study vaccine is designed to help prepare the immune system to fight the real COVID-19 virus if it enters the body.</p>\n
      • short_titleRecombinant COVID-19 vaccine
      • protocol_noECCT/21/03/01
      • version_no1,0
      • date_of_protocol19-02-2021
      • study_drugRecombinant COVID-19 Vaccine (Sf9 cells)
      • disease_conditionPrevention of COVID-19 caused by infection with the SARS-CoV-2.
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_nameRecombinant COVID-19 vaccine (Sf9 cells)
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjnyange@kaviuon.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
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      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
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      • applicant_participating_countries(null)
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      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantProf Walter Jaoko
      • declaration_date111-03-2021
      • declaration_principal_investigatorN/A
      • declaration_date211-03-2021
      • placebo_presentYes
      • study_objectives<p>\n 1. Efficacy of recombinant COVID-19 vaccine (Sf9 cells) in preventing virologically confirmed (PCR positive) symptomatic COVID-19 2. Safety of recombinant COVID-19 vaccine (Sf9 cells) in terms of SAE, MAAE and AESI in all participants from Day 0 through 6 months after completion of 3 vaccination doses3.  Efficacy of recombinant COVID-19 vaccine (Sf9 cells) in preventing virologically confirmed (PCR positive) symptomatic COVID-19 4. Efficacy of recombinant COVID-19 vaccine (Sf9 cells) in preventing severe COVID-19 or death caused by SARS-CoV-2 infection 5. Efficacy of recombinant COVID-19 vaccine (Sf9 cells) in preventing virologically confirmed (PCR positive) hospitalised moderate, severe COVID-19 and death caused by SARS-CoV-2 infection</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n Inclusion criteria  Aged 18 years and older.  Able and willing (in the investigator’s opinion) to comply with all study requirements.  Willing to allow the investigators to discuss the volunteer’s medical history with their general practitioner/personal doctor and access all medical records which are relevant to study procedures.  Healthy adults, or stable-healthy adults who may have a pre-existing medical condition that does not meet any exclusion criteria. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrolment.  For females of childbearing potential only, willingness to practice continuous effective contraception (see glossary) for 90 days after completion of 3 vaccination doses, and have negative pregnancy tests before each vaccination dose. Note: Nonchildbearing potential is defined as surgically sterile (history of bilateral tubal ligation, bilateral oophorectomy, hysterectomy) or postmenopausal (defined as amenorrhea for ≥ 12 consecutive months prior to screening without an alternative medical cause). A follicle-stimulating hormone (FSH) level may be measured at the discretion of the investigator to confirm postmenopausal status.  Males participating in this study who are involved in heterosexual sexual activity must agree to practice adequate contraception (see glossary) and refrain from donating sperm for 90 days after receiving the study vaccination.  Agreement to refrain from blood donation during the study.  Provide written informed consent form (ICF).</p>\n
      • principal_exclusion_criteria<p>\n Exclusion criteria for the first dose  Participation in any other COVID-19 prophylactic drug trials during the duration of the study. Note: Participation in COVID-19 treatment trials is allowed in the event of hospitalization due to COVID-19. The study team should be informed as soon as possible.  Positive HIV antibody testing results.  Participation in SARS-CoV-2 serological surveys where participants are informed of their serostatus during the duration of the study. Note: Disclosure of serostatus post enrolment may accidentally unblind participants to group allocation. Participation in this trial can only be allowed if volunteers are kept blinded to their serology results from local/national serological surveys  Planned receipt of any licensed or investigational vaccine, other than the study intervention, within 14 days before and after study vaccination.  Prior receipt of an investigational or licensed COVID-19 vaccine.  Administration of immunoglobulins and/or any blood products within three months prior to the planned administration of the investigational products (IPs).  Any confirmed or suspected immunosuppressive or immunodeficient state; positive HIV status; asplenia; recurrent severe infections and chronic use (more than 14 days) of immunosuppressant medication within the past 6 months. Topical steroids or short-term (course lasting ≤14 days) oral steroids are not an exclusion criteria.  History of allergic disease or reactions likely to be exacerbated by any component of Recombinant COVID-19 Vaccine (Sf9 cells).  Any history of angioedema  Pregnancy, lactation or willingness/intention to become pregnant within 90 days after receiving study vaccine  Current diagnosis or treatment of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)  History of serious psychiatric condition likely to affect participation in the study  Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture  Suspected or known current alcohol or drug dependency  Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness (mild/moderate well-controlled comorbidities are allowed)  History of laboratory-confirmed COVID-19  Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban)  Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data. Exclusion criteria for the second/third dose In this trial, the second/third vaccination dose may be terminated in some cases. These include systemic allergic reactions, severe hypersensitivity reactions, or intolerable grade 3 or higher adverse reactions after the previous vaccination/placebo. If these reactions occur, the participants should not continue to receive the second/third vaccination.</p>\n
      • primary_end_points<p>\n Primary Safety Endpoint: 1. The incidence of serious adverse events (SAE) from Day 0 through 6 months after completion of 3 vaccination doses in all participants in the Recombinant COVID-19 vaccine (Sf9 cells) group compared to the placebo group. 2. The incidence of medically attended adverse events (MAAE) from Day 0 through 6 months after completion of 3 vaccination doses in all participants in the Recombinant COVID-19 vaccine (Sf9 cells) group compared to the placebo group. 3. The incidence of adverse events of special interest (AESI) from Day 0 through 6 months after completion of 3 vaccination doses in all participants in the Recombinant COVID-19 vaccine (Sf9 cells) group compared to the placebo group. Data from all participants will be used to assess the primary safety endpoint.</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 Number of Staff: 1 physician, I pharmacist, 3pharmacy staff, 4 trial clinicians, 7 nurse counselors, 4 community staff, 1 data IT/Data manager, 3 Data staff and 8 lab staff, I labaratory Manager Core Staff: 1. Dr. Gloria Omosa Manyonyi  MBChB MPH Sub- Investigator 2. Dr Moses Masika MBChB MSc TID,Laboratory Manager 3 Rose Sajabi KRCHN, BA, MA Counselling PSY Study Coordinator,4. Jacquelyn Nyange RN, BA, MSc. Clinical PSY Regulatory compliance Site Facities: Clinic, Labaratory, data and Pharmacy space available on site Emergency Facities: Well equiped Emergecy room in the clinic</p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n N/AN/A</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration2 YEARS
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorSodium chloride
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKAVI-institute of Clinical Research
      • single_site_physical_addressCollege of health sciences University of Nairobi, KNH campus
      • single_site_contact_personProf Walter Jaoko
      • single_site_telephone0727 555 254
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states4 states
      • number_of_sites
      • multi_country_listKENYA, INDONESIA, NEPAL AND UZBEKISTAN
      • data_monitoring_committeeYes
      • total_enrolment_per_site400
      • total_participants_worldwide40,000
      • 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_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • 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_nameN/A
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      • investigator1_family_nameN/A
      • investigator1_qualificationN/A
      • investigator1_professional_addressN/A
      • investigator1_telephoneN/A
      • investigator1_emailWjaoko@kavioun.org
      • organisations_transferred_No
      • number_participants400
      • notification<p>\n None</p>\n
      • approval_date13-05-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted01-04-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe application has been approved by the experts
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      • balance_site(null)
      • final_date(null)
      • modified2025-07-16 13:31:03
      • created2021-03-11 07:17:22
      • total_sites(null)
      • ecitizen_invoice(null)
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      • 0(array)
        • id628
        • application_id984
        • given_nameWalter Jaoko
        • middle_name
        • family_nameJaoko
        • qualificationMBChB, MTropMed, PhD, PGD (Health Research Ethics
        • professional_addressDirector, KAVI-Institute of Clinical Research, Dept. of Medical Microbiology, University of Nairobi
        • telephone+254 727 555 254
        • emailWjaoko@kaviuon.org
        • created2021-03-11 07:25:29
        • modified2021-04-01 15:42:00
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        • application_id984
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        • created2021-03-11 07:25:29
        • modified2021-04-01 15:42:00
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id484
        • application_id984
        • sponsorChengdu WestVac Biopharm Co., Ltd.
        • sponsor_typeOthers
        • contact_personYuquan Wei
        • addressChengdu Tianfu International Biological City (618 Phoenix Road, Shuangliu District), China 610219 West China Hospital of Sichuan University No. 17, Section 3, Renmin South Road, Chengdu, China 610041
        • telephone_numberTel: 86-13808014326/+86-18980601789
        • fax_numberFax: 86-28-85502796
        • cell_numberTel: 86-13808014326/+86-18980601789
        • email_addressyqwei@vip.sina.com
        • created2021-03-11 07:25:29
        • modified2021-04-01 15:42:00
  • 1(array)
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      • id1542
      • user_id263
      • trial_status_id2
      • abstract_of_study<div>\n SCD is caused by a specific point mutation (E6V) in the gene encoding hemoglobin (Hb) subunit beta that leads to the production of abnormal Hb (“sickle hemoglobin” or HbS). Sickled haemoglobin leads to several patho-physiological changes that culminates in the vascular obstruction and ischemia responsible for much of the observed morbidity in SCD. Prior to July 2017, the only drug specifically approved for the treatment of SCD was hydroxyurea (HU). HU reduces painful crises and the need for blood transfusions at least in part by increasing levels of fetal hemoglobin (HbF), which reduces RBC sickling and improves blood flow. Unfortunately, HU is often poorly tolerated, and its widespread use is limited by concerns about its potential impact on fertility and reproduction, challenges achieving and maintaining an efficacious dose due to its hematologic toxicities, and requirements for monthly monitoring.</div>\n<div>\n  </div>\n<div>\n In the US, recently approved treatment options include L-glutamine, voxelotor, and crizanlizumab-tmca. L-glutamine is indicated to reduce the acute complications of SCD, though its adoption remains somewhat limited by lingering questions regarding limitations of the clinical studies, cost concerns, potential for reduced adherence due to twice-daily administration. Voxelotor leads to increased Hb O2 affinity along with a reduction in clinical markers of hemolysis and an increase in Hb levels. Crizanlizumab-tmca administered via intravenous (IV) infusion, has been shown to reduce the incidence of VOCs in patients with SCD. While these new therapies provide promise, additional therapies with the potential to target the underlying pathophysiology of SCD are still needed to manage patients with this devastating disease.</div>\n<div>\n  </div>\n<div>\n Etavopivat is a potent and effective activator of pyruvate kinase red blood cell PKR in both human and mouse red blood cells (RBC). The potential clinical consequence of PKR activation was demonstrated in cellular assays with RBC from patients with SCD in which etavopivat increased haemoglobin-oxygen (Hb-O2) affinity and reduced sickling under severe hypoxic conditions. The study is made up of two parts:</div>\n<div>\n •<strong> Double-blind treatment period</strong>: Research patients will take the study drug (etavopivat or placebo, depending on which treatment group they are in) for 52 weeks. This part of the study is “double-blind,” meaning neither the patient nor study doctor will know which specific treatment (etavopivat or placebo) the patient is receiving. For every 1 participant receiving a placebo, two will receive etavopivat.</div>\n<div>\n <strong>• Open-label extension: </strong>Patients who complete the double-blind treatment period will be eligible to receive etavopivat in the 52-week open-label extension. In this part of the study, the participant will receive etavopivat even if he/she was assigned to receive placebo in the double-blind treatment period.</div>\n<div>\n  </div>\n<div>\n This is an interventional, multi-national, multi-centre, randomised (2:1), double-blind, placebo controlled, Phase 3 study in participants aged 12 and older with sickle cell disease (SCD), who had 2−15 vaso-occlusive crises (VOCs) in the year prior to screening and who have moderate to severe anaemia. This study will enroll up to approximately 408 adult and adolescent patients with SCD, including a maximum of 100 in the age group 12 to 17 years. Kenya is expected to contribute a total of 67 participants to the study population. </div>\n<div>\n  </div>\n<div>\n Participants will be seen at the study sites at week 2 and week 6 then approximately every 6 weeks until week 52 which is the End of Blinded Treatment in the study. Participants in the open-label extension will have visits at weeks 52,56,60,68,76,84,92 and 104. Week 104 is the end of study treatment and will be followed by an end of study visit after 4 weeks. Safety will be monitored throughout the study, and PD, QoL, and clinical outcome measures will be performed at specified visits.</div>\n
      • study_title<p>\n A global phase 3, randomised, double-blind and placebo-controlled study evaluating the efficacy and safety of etavopivat in adolescents and adults with sickle cell disease.</p>\n
      • laymans_summary<div>\n <strong>What is the problem/background?</strong></div>\n<div>\n Sickle cell disease (SCD) is a disease that can be passed on from both parents to a child. It affects the red blood cells that carry oxygen to the body. Normal red blood cells have a circular shape and are very flexible. For patients with SCD, their red blood cells can look like a sickle or crescent moon and become very stiff. These sickle-shaped red blood cells can get stuck in the blood vessels leading to early destruction of these abnormal red blood cells.</div>\n<div>\n <div>\n These blocked blood vessels and loss of red blood cells makes it hard for the blood to transport oxygen. The lack of oxygen can cause severe body pains, which is a key symptom of SCD. </div>\n <div>\n These results in the manifestation of SCD including; recurrent pain referred to as a painful vaso-occlusive crisis (VOC), low blood level and organ damage. </div>\n <div>\n Before 2017, the only known medication approved for preventing the painful episodes and other SCD problems was hydroxyurea. Hydroxyurea works by reducing the number of the sickle red blood cells.</div>\n <div>\n <p>\n Sickle cell disease is associated with significant burden in quality of life. The cure is not readily and locally available. The available medications include drugs for; pain relief, boosting low blood level, prevention of infection and vaccination to prevent infection that is common in Sickle Cell Disease. They are also provided with mental and social support. However, despite these treatments, people with Sickle Cell Disease continue to suffer due to problems of SCD resulting in early death because, none of them results in both significant improvement of blood level and a reduction in the rate of pain episodes and other SCD problems. More research and development of SCD treatments are necessary to improve the effects of the disease and quality of life of the Sickle cell patients.</p>\n </div>\n <div>\n  </div>\n <div>\n <strong>What questions is the study trying to answer?</strong></div>\n <div>\n Etavopivat is a small molecule that can activate a specific protein found in the red blood cells. This protein helps the red blood cells to make energy and to bind oxygen, ultimately improving the health of the red blood cells. These effects may help in treating blood disorders such as sickle cell disease.</div>\n <div>\n The objective of the present study is to confirm how well and how safe etavopivat is compared to placebo on annualised vaso-occlusive crises (VOC) rates, measures of end organ damage,functional exercise capacity, as measured by the 6-minute walk test, and quality of life measures (including fatigue) in adolescents and adults with sickle cell disease enrolled in the study.</div>\n <div>\n A placebo is a medication with similar physical characteristics (shape, color, taste, packing) as the etavopivat but does not contain any active chemical ingredients that affect the body.</div>\n <div>\n  </div>\n <div>\n <strong>Where is the study taking place, how many people does it involve and how are they selected?</strong></div>\n <div>\n The study will be conducted in many centres across the world including at 4 sites in Kenya, in children aged 12 years and above and adult patients aged 18 years and older with 2-15 VOC. Globally, about 408 patients will be enrolled into the study. Kenya is expected to contribute a total of 67 participants to the study population.  Of 408 participants, up to 100 participants will be children and teenagers between 12 and 17 years old, with approximately 25 expected to be enrolled across the 4 sites in Kenya.</div>\n <div>\n  </div>\n <div>\n <strong>What does the study involve for those who are in it?</strong></div>\n <div>\n The participants will be asked to come to 20 visits at the clinic. The participants will have physical examinations as well as other tests, including a walking exercise, heart checks and blood and urine tests. During specific clinic visits, participants will be asked to answer short questionnaires about their health and quality of life. In some countries, participants may also have additional blood samples collected for future research if they accept to do so. Every day during the study, participants will use the Study App to register when they took the study medicine and register if they had any sickle cell pain.</div>\n <div>\n Participants will have a two times chance to receive the etavopivat or the placebo in the first 52 weeks of the study after which they will all receive etavopivat for another 52 weeks. Etavopivat or placebo will be taken once a day for the entire duration of the study.</div>\n <div>\n  </div>\n <div>\n <strong>What are the benefits and risks/costs of the study for those involved?</strong></div>\n <div>\n Necessary precautions have been put in the design and planned conduct of this study in order to minimise risks and inconveniences of participation. The etavopivat safety data, deriving from the nonclinical safety studies and data from Phase 1 studies and the Phase 2 part of study 4202-HEM-301, have not identified major safety issues. Together with the benefit data that has been gathered and presented, this supports further clinical development of etavopivat and suggests that participants with SCD enrolled in this study have the potential to benefit from treatment with etavopivat and that such benefits could be clinically meaningful. The research study will be done at no cost to the participants and they will be reimbursed for “out-of-pocket” expenses, such as travel costs as well as for time spent, meals and inconvenience.</div>\n <div>\n  </div>\n <div>\n <strong>How will the study benefit society?</strong></div>\n <div>\n By participating in the study, the participants will help contribute to the new information on the dosage and usefulness of etavopivat in the management of SCD. Upon public availability of the study results, the results will be disseminated to various community stakeholders.</div>\n <div>\n  </div>\n <div>\n <strong>When does the study start and finish?</strong></div>\n <div>\n The study will start as soon as ethical approval is received. Duration of study participation for an individual patient may last up to 112 weeks and includes the screening period (up to 4 weeks before study treatment), the double-blind treatment period of the study for up to 52 weeks, participation in the open-label extension treatment period for up to 52 weeks and an End of Study (EOS) visit at 4 weeks after the last dose of study drug.</div>\n</div>\n<p>\n  </p>\n
      • short_titleHibiscus 2 - Site 252
      • protocol_noECCT/25/05/05
      • version_no3
      • date_of_protocol30-09-2024
      • study_drugEtavopivat
      • disease_conditionSickle 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_nameetavopivat
      • 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_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_applicantNatasha Boshoff
      • declaration_date128-05-2025
      • declaration_principal_investigatorDr Videlis Nduba - PI
      • declaration_date228-05-2025
      • placebo_presentYes
      • study_objectives<div>\n The objective of the present study is to confirm efficacy and safety of etavopivat (compared to</div>\n<div>\n placebo) on annualised vaso-occlusive crises (VOC) rates, measures of end organ damage,</div>\n<div>\n functional exercise capacity, as measured by the 6-minute walk test (6MWT), and quality of life</div>\n<div>\n (QOL) measures (including fatigue) in adolescents and adults with sickle cell disease (SCD)</div>\n<div>\n enrolled in the study. Additional Patient Reported Outcome (PRO) QOL measures, including pain,</div>\n<div>\n emotional and functional impact, will also be used to confirm efficacy of etavopivat in adult and</div>\n<div>\n adolescents with SCD. These results are intended to support additional clinical studies within the</div>\n<div>\n etavopivat SCD program.</div>\n
      • principal_inclusion_criteria<div>\n  </div>\n<div>\n <ol>\n <li>\n Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.</li>\n <li>\n Male or female.</li>\n <li>\n Age 12 years or above at the time of signing the informed consent.</li>\n <li>\n Confirmed diagnosis of sickle cell disease.\n <ul>\n <li>\n Documentation of sickle cell disease (SCD) genotype (sickle cell haemoglobin (HbSS), HbSβ0-thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing or screening test results from central laboratory. Molecular genotyping is not required. SCD genotype may be determined from the results of haemoglobin (Hb) electrophoresis, high-performance liquid chromatography (HPLC) or similar testing. Note that Hb electrophoresis is performed by the central laboratory at screening.</li>\n </ul>\n </li>\n <li>\n Have 2−15 episodes of documented VOC (defined in protocol section 8.2.2) within the 12 months prior to screening. Documentation must exist in the participant’s medical record prior to randomisation. Events based solely on participant recall without supporting documentation should not be counted towards eligibility.</li>\n <li>\n Hb ≥5.0 and ≤10.0 g/dL (≥50 and ≤100 g/L) at screening.</li>\n <li>\n Participants on hydroxyurea (HU) treatment at the time of consent may be eligible if they:\n <ul>\n <li>\n Have been on a stable dose (no more than a 20% change in dosing) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments during the study (except for weight-based changes)</li>\n <li>\n and have been ≥80% compliant with planned regimen prior to the time of consent, at the discretion of the investigator.</li>\n </ul>\n </li>\n <li>\n Participants on l-glutamine oral powder (Endari®) treatment at the time of consent may be eligible if they:\n <ul>\n <li>\n Have been on a stable dose for ≥12 months at the time of consent (i.e., no changes to the dose except for changes to weight or for safety reasons) and</li>\n <li>\n Have been ≥80% compliant with the planned regimen during the 12 months prior to the time of consent, at the discretion of the investigator.</li>\n </ul>\n </li>\n </ol>\n</div>\n<ol>\n <li>\n Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.</li>\n <li>\n Male or female.</li>\n <li>\n Age 12 years or above at the time of signing the informed consent.</li>\n <li>\n Confirmed diagnosis of sickle cell disease.\n <ul>\n <li>\n Documentation of sickle cell disease (SCD) genotype (sickle cell haemoglobin (HbSS), HbSβ0-thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing or screening test results from central laboratory. Molecular genotyping is not required. SCD genotype may be determined from the results of haemoglobin (Hb) electrophoresis, high-performance liquid chromatography (HPLC) or similar testing. Note that Hb electrophoresis is performed by the central laboratory at screening.</li>\n </ul>\n </li>\n <li>\n Have 2−15 episodes of documented VOC (defined in protocol section 8.2.2) within the 12 months prior to screening. Documentation must exist in the participant’s medical record prior to randomisation. Events based solely on participant recall without supporting documentation should not be counted towards eligibility.</li>\n <li>\n Hb ≥5.0 and ≤10.0 g/dL (≥50 and ≤100 g/L) at screening.</li>\n <li>\n Participants on hydroxyurea (HU) treatment at the time of consent may be eligible if they:\n <ul>\n <li>\n Have been on a stable dose (no more than a 20% change in dosing) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments during the study (except for weight-based changes)</li>\n <li>\n and have been ≥80% compliant with planned regimen prior to the time of consent, at the discretion of the investigator.</li>\n </ul>\n </li>\n <li>\n Participants on l-glutamine oral powder (Endari®) treatment at the time of consent may be eligible if they:\n <ul>\n <li>\n Have been on a stable dose for ≥12 months at the time of consent (i.e., no changes to the dose except for changes to weight or for safety reasons) and</li>\n <li>\n Have been ≥80% compliant with the planned regimen during the 12 months prior to the time of consent, at the discretion of the investigator.</li>\n </ul>\n </li>\n</ol>\n
      • principal_exclusion_criteria<p style=\"margin-left: 6.8pt;\">\n 1. Known or suspected hypersensitivity to study intervention or related products.</p>\n<p style=\"margin-left: 6.8pt;\">\n 2. Previous dosing in this study or participated in other etavopivat trials.</p>\n<p style=\"margin-left: 6.8pt;\">\n 3. More than one rescreening for this study as specified in 5.4 of study protocol.</p>\n<p style=\"margin-left: 6.8pt;\">\n 4. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using adequate contraceptive method, as defined in Appendix 4 (Section 10.4) of study protocol. Pregnancy test must be negative at screening and day of randomisation.</p>\n<p style=\"margin-left: 6.8pt;\">\n 5. Participation (i.e., signed informed consent) in any other interventional clinical study within 28 days or 5 half-lives of trial product, whichever is longer, before dosing.</p>\n<p style=\"margin-left: 6.8pt;\">\n 6. Use of voxelotor or similar agent within 28 days prior to starting study treatment or anticipated need for this agent during the study.</p>\n<p style=\"margin-left: 6.8pt;\">\n 7. Use of a selectin antagonist (e.g., crizanlizumab, monoclonal antibody or small molecule) within 28 days or 5 half-lives (whichever is longer) prior to starting study treatment or anticipated need for such agents during the study.</p>\n<p style=\"margin-left: 6.8pt;\">\n 8. Receiving regularly scheduled blood (red blood cells - RBC) transfusion therapy (also termed chronic, prophylactic or preventive transfusion) or ≥ 6 transfusion events in the previous 12 months (i.e., an average of 1 transfusion event every 60 days).</p>\n<p style=\"margin-left: 6.8pt;\">\n 9. Participants who have received an RBC transfusion for any reason within 90 days prior to the screening visit are only eligible if HbA (adult Hb) <10% by Hb electrophoresis is documented prior to starting study treatment.</p>\n<p style=\"margin-left: 6.8pt;\">\n 10. Receiving or use of concomitant medications that are strong inducers of CYP3A4 (see Section 6.8) within 2 weeks of starting study treatment or anticipated need for such agents during the study.</p>\n<p style=\"margin-left: 6.8pt;\">\n 11. Use of erythropoietin or other haematopoietic growth factor treatment within 28 days of starting study treatment or anticipated need for such agents during the study.</p>\n<p style=\"margin-left: 6.8pt;\">\n 12. Receipt of prior cellular-based therapy (e.g., haematopoietic cell transplant, gene modification therapy).</p>\n<p style=\"margin-left: 6.8pt;\">\n 13. Hepatic dysfunction characterized by:</p>\n<ul>\n <li>\n Alanine aminotransferase (ALT) >4.0 × upper limit of normal (ULN) or</li>\n <li>\n Direct bilirubin >3.0 × ULN.</li>\n</ul>\n<p style=\"margin-left: 6.8pt;\">\n 14. Participants with active and clinically significant bacterial, fungal, parasitic or viral infection requiring systemic therapy at time of screening or randomisation. If infection is acute, participants should delay screening until active therapy has been completed.</p>\n<p style=\"margin-left: 6.8pt;\">\n Note: Infection prophylaxis is allowed and may be required in some regions of the world where malaria is endemic</p>\n<p style=\"margin-left: 6.8pt;\">\n 15. Participants who are not taking or are unable to take antimalarial prophylaxis at the time of consent and during the study if they live in areas of endemic malaria where prophylaxis is recommended.</p>\n<p style=\"margin-left: 6.8pt;\">\n 16. Diagnostic test results positive for human immunodeficiency virus (HIV) type 1 (HIV-1) or HIV-2 infection.</p>\n<p style=\"margin-left: 6.8pt;\">\n 17. Active infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and hepatitis B core antibody [HepBcAb] positive).</p>\n<p style=\"margin-left: 6.8pt;\">\n 18. Active hepatitis C (HepC) infection (HepC Ab positive with positive HepC PCR).</p>\n<p style=\"margin-left: 6.8pt;\">\n 19. Severe renal dysfunction (estimated glomerular filtration rate [eGFR] at screening, calculated by the central laboratory <30 mL/min/1.73 m2) or on chronic dialysis.</p>\n<p style=\"margin-left: 6.8pt;\">\n 20. Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix or in situ prostate cancer) within 5 years prior to screening.</p>\n<p style=\"margin-left: 6.8pt;\">\n 21. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:</p>\n<ul>\n <li>\n Unstable angina pectoris or myocardial infarction or elective coronary intervention.</li>\n <li>\n Congestive heart failure requiring hospitalization.</li>\n <li>\n Uncontrolled clinically significant arrhythmias.</li>\n <li>\n Any history of overt clinical stroke.</li>\n</ul>\n<p style=\"margin-left: 6.8pt;\">\n 22. Presence of clinically significant gastrointestinal disorders potentially affecting absorption of trial product and/or nutrients, as judged by the investigator. This includes major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable).</p>\n<p style=\"margin-left: 6.8pt;\">\n 23. Participants with iron deficiency (e.g., serum iron less than the lower limit of normal</p>\n<p style=\"margin-left: 6.8pt;\">\n [LLN] or ferritin <10 µg/L) who are not taking or are unable to take iron supplements at the time of consent and during the study or if there is a concern for gastrointestinal bleed as the cause. Participants with low serum iron levels due to chronic inflammation or other causes in which supplemental iron therapy is not indicated are not excluded.</p>\n<p style=\"margin-left: 6.8pt;\">\n 24. Participants with folate (or folic acid or Vitamin B9) or Vitamin B12 deficiency</p>\n<p style=\"margin-left: 6.8pt;\">\n (e.g., folate or Vitamin B12 levels less than the LLN) who are not taking or are unable to take supplements before the first dose of trial product and during the study.</p>\n<p style=\"margin-left: 6.8pt;\">\n 25. History of deep venous thrombosis requiring systemic anti-coagulation therapy for</p>\n<p style=\"margin-left: 6.8pt;\">\n ≥6 weeks, occurring within 6 months prior to randomisation.</p>\n<p style=\"margin-left: 6.8pt;\">\n Note: participants on ≥6 months of chronic or prophylactic anti-coagulation therapy are allowed in the study. </p>\n<p style=\"margin-left: 6.8pt;\">\n 26. Any disorder, unwillingness, or inability which in the investigator’s opinion, might jeopardise the participant’s safety or compliance with the protocol.</p>\n<p style=\"margin-left: 6.8pt;\">\n 27. Mental incapacity, language barriers or unwillingness to comply with the requirements of the protocol, which may preclude adequate understanding or co-operation during the study as judged by the investigator.</p>\n<p style=\"margin-left: 6.8pt;\">\n 28. Inadequate venous access as determined by the investigator or site staff.</p>\n<p style=\"margin-left: 6.8pt;\">\n 29. Anticipated change in lifestyle (e.g., eating, exercise or sleeping pattern) during the study.</p>\n<p style=\"margin-left: 6.8pt;\">\n 30. Six-minute walking distance on standardized 6MWT below 100 m at screening.</p>\n<p style=\"margin-left: 6.8pt;\">\n 31. Any surgery scheduled for the duration of the study, or other indications, that would impact walking ability at the discretion of the investigator.</p>\n
      • primary_end_points<p style=\"margin-left: 6.8pt;\">\n <strong>Primary</strong></p>\n<p style=\"margin-left: 6.8pt;\">\n Number of adjudicated vaso-occlusive crises (VOC) events with a medical contact^a</p>\n<p style=\"margin-left: 6.8pt;\">\n  </p>\n<p style=\"margin-left: 6.8pt;\">\n <strong>Secondary</strong></p>\n<p style=\"margin-left: 6.8pt;\">\n Confirmatory</p>\n<ul>\n <li>\n Change in haemoglobin (Hb) >1 g/dL (yes/no)</li>\n <li>\n Time to onset of first adjudicated VOC^a</li>\n <li>\n Change in distance travelled during the 6-minute walking test (6MWT)</li>\n <li>\n Change in standardised T-score on the PROMIS Fatigue 7a Scale</li>\n</ul>\n<p style=\"margin-left: 6.8pt;\">\n  </p>\n<p style=\"margin-left: 6.8pt;\">\n a. See protocol section 8.2.2 for description.</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 <u><strong>Site 252 – KEMRI-CRDR Siaya Site</strong></u></p>\n<p style=\"margin-left: 6.2pt;\">\n KEMRI/CRDR Siaya Clinical Research Annex is located in Siaya County within Siaya County Referral Hospital Grounds. Siaya County is located about 70 km West of Kisumu. The administrative offices of the PI, Procurement and Human Resource functions are housed at the KEMRI Kisian Campus. KEMRI has a modern research annex at with capacity to conduct Phase I to Phase IV studies through training and experience.</p>\n<p style=\"margin-left: 6.2pt;\">\n After community mobilization, recruitment, screening and enrollment, Investigational Product storage and dispensation and follow-up study activities will occur at the study clinic.</p>\n<p style=\"margin-left: 6.2pt;\">\n Site investigators responsible for day to day running of the project includes: the Principal Investigator-Study oversight, 2 Medical Officers- Medical Officers do eligibility, randomization, supervise the study clinicians who do safety assessments, and safety assessment and reporting during follow up, 2 Pharmacists and 2 Pharmaceutical technologists-IP management, 6 Nurses- vital signs and anthropometric assessments, 6 Quality Assurance/Quality Control Officers- quality check of site processes and documentations and ethics/ regulatory authority submissions, 4 Clinical Officers-eligibility assessments and safety assessments during screening and follow up, 7 Community Interviewers- Community engagement team does community mobilization, participant recruitment and retention activities, 4 Data personnel- Data team does local system maintenance, data transcription and support all other departments with internet services, 3 administrative officers- do administrative activities and 5 Laboratory Personnel- Laboratory team does biological sample management.</p>\n<p style=\"margin-left: 6.2pt;\">\n <strong>Prof. </strong><strong>Videlis Nduba</strong><strong>, Principal Investigator</strong></p>\n<p style=\"margin-left: 6.2pt;\">\n Will be responsible for the overall conduct of the trial at this study site, administrative actions between site, Institutional Review Boards, and the sponsor, oversight of site activities and clinical care provision to study participants. He will contribute to the writing of the scientific report.</p>\n<p style=\"margin-left: 6.2pt;\">\n <strong>Dr.  </strong><strong>Mercy Mwale</strong><strong>, Dr. Mike Odoyo, Sub- Investigator</strong></p>\n<p style=\"margin-left: 6.2pt;\">\n Will be responsible for the clinical conduct of the trial, the care provided to patients, oversight of study activities at the site. Reviewing potential Study participants for eligibility, supervising Clinical Officers, review of laboratory results, adverse events and serious adverse events surveillance, documentation and reporting, providing first hand clinical care to participants. Data entry.</p>\n<p style=\"margin-left: 6.2pt;\">\n <strong>Dr. Emily Naiserian Nyakeriga Pharmacist</strong></p>\n<p style=\"margin-left: 6.2pt;\">\n Application of import license for Investigational Products, IMP accountability from receipt to storage, cold chain maintenance, preparation and dispensing and accountability logs, and IMP destruction. Supervision of the Pharmaceutical Technologists at each of the study sites.</p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width: 162px; height: 34px;\">\n <p align=\"center\">\n <strong>Site Staff Name</strong></p>\n </td>\n <td style=\"width: 153px; height: 34px;\">\n <p align=\"center\">\n <strong>Designation</strong></p>\n </td>\n <td style=\"width: 172px; height: 34px;\">\n <p align=\"center\">\n <strong>Qualification</strong></p>\n </td>\n <td style=\"width: 162px; height: 34px;\">\n <p align=\"center\">\n <strong>Experience</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n Prof Videlis Nduba</p>\n </td>\n <td style=\"width: 153px; height: 18px;\">\n <p>\n PI</p>\n </td>\n <td style=\"width: 172px; height: 18px;\">\n <p>\n MBChB, PhD</p>\n </td>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n 16 years</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n Dr. Mercy Muderi Mwale</p>\n </td>\n <td style=\"width: 153px; height: 18px;\">\n <p>\n Sub-Investigator</p>\n </td>\n <td style=\"width: 172px; height: 18px;\">\n <p>\n MBChB</p>\n </td>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n 4 years</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n Dr. Mike Onyango Odoyo</p>\n </td>\n <td style=\"width: 153px; height: 18px;\">\n <p>\n Sub-Investigator</p>\n </td>\n <td style=\"width: 172px; height: 18px;\">\n <p>\n MBChB</p>\n </td>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n 2 years</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n Emily Nyakeriga</p>\n </td>\n <td style=\"width: 153px; height: 18px;\">\n <p>\n Study Pharmacist</p>\n </td>\n <td style=\"width: 172px; height: 18px;\">\n <p>\n BPharm</p>\n </td>\n <td style=\"width: 162px; height: 18px;\">\n <p>\n 4 years</p>\n <div>\n  </div>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The trial will not be conducted in the Sponsor country (Denmark) due to the very limited number of participants with Sickle Cell Disease.</p>\n
      • other_details_regulatory_notapproved<ul>\n <li style=\"margin-left: 7.1pt;\">\n Saudi Food & Drug Authority (SFDA) - Saudi Arabia: 04 Nov 2024</li>\n <li style=\"margin-left: 7.1pt;\">\n National Agency for Food and Drug Administration and Control (NAFDAC) - Nigeria: 14 Nov 2024</li>\n <li style=\"margin-left: 7.1pt;\">\n Food and Drugs Authority (FDA) - Ghana: 18 Nov 2024</li>\n <li style=\"margin-left: 7.1pt;\">\n European Medicines Agency (EU Clinical Trial Regulation) - European Union: 11 Nov 2024</li>\n <li style=\"margin-left: 7.1pt;\">\n Uganda National Drug Authority - Uganda: 25 Mar 2025</li>\n</ul>\n
      • other_details_regulatory_approved<p style=\"margin-left: 8.65pt;\">\n Initial Health Authority approvals have been received in the following countries for the current study (NN7535-7807):</p>\n<ul>\n <li style=\"margin-left: 7.1pt;\">\n USA - 15 June 2024* (47 sites)</li>\n <li style=\"margin-left: 7.1pt;\">\n Canada – 12 August 2024  (8 sites)</li>\n <li style=\"margin-left: 7.1pt;\">\n Australia – 26 August 2024 (6 sites)</li>\n <li style=\"margin-left: 7.1pt;\">\n UK – 13 September 2024 (6 sites)</li>\n <li style=\"margin-left: 7.1pt;\">\n Brazil – 10 October 2024 (6 sites)</li>\n <li style=\"margin-left: 7.1pt;\">\n India - 20 November 2024 (14 sites)</li>\n <li style=\"margin-left: 7.1pt;\">\n Turkey - 19 December 2024 (5 sites)</li>\n</ul>\n<p style=\"margin-left: 7.1pt;\">\n *The US FDA does not issue approval letters for protocols. According to the Code of Federal Regulations, an IND applicant may proceed with a clinical investigation once the applicant has been notified by the FDA that the investigation may proceed, or after 30 days if the IND is not placed on Clinical Hold. As of 31 January 2024, there has not been communication of a clinical hold from the FDA.</p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration52 weeks
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • 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_states21
      • number_of_sites4
      • multi_country_listAustralia, Belgium, Brazil, Canada, Columbia, France,\nGhana, Greece, India, Italy, Lebanon, Kenya, Netherlands, Nigeria, Oman, Saudi Arabia,\nSpain, Turkey, Uganda, United Kingdom, USA
      • data_monitoring_committeeYes
      • total_enrolment_per_siteCompetitive enrolment with a maximum of 16 patients per site:\n1. Dr Ogutu – 16\n2. Dr Nduba - 16\n3. Dr Chite Asirwa - 16\n4. Dr Mutua – 16
      • total_participants_worldwide408
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • 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_consentYes
      • subjects_specifyConsent of pediatric participants (below 18 years of age) is obtained by means of parents or legally acceptable representatives
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBernhards
      • investigator1_middle_name
      • investigator1_family_nameOgutu
      • investigator1_qualificationMBCHB, PHD
      • investigator1_professional_addressAhero Clinical Trails Unit, CREATES Strathmore University, PO.Box 54-40100, Kisumu, Kenya
      • investigator1_telephone+254 733812613 / +254733966065
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_Yes
      • number_participantsApproximately 67 from 4 sites
      • notification
      • approval_date15-10-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted19-05-2025
      • is_child0
      • unsubmitted1
      • initial_date_submitted19-05-2025
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed. Prof Kokwaro (Email approval) and Kimotho approved.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-10-15 18:08:31
      • created2025-05-14 10:39:18
      • total_sites1
      • ecitizen_invoice371383
    • InvestigatorContact(array)
      • 0(array)
        • id1272
        • application_id1542
        • given_nameVidelis
        • middle_name
        • family_nameNduba
        • qualificationMBCHB, PhD
        • professional_addressKEMRI CRDR Siaya Clinical Research Annex, P.O. Box 144-40600, Siaya, Kenya
        • telephone+254 724 522 474
        • emailvnduba@gmail.com
        • created2025-05-14 10:42:17
        • modified2025-05-28 15:01:56
    • SiteDetail(array)
      • 0(array)
        • id1900
        • application_id1542
        • county_id41
        • site_nameKEMRI CRDR Siaya Clinical Research Annex
        • physical_addressKEMRI CRDR Siaya Clinical Research Annex, P.O. Box 144-40600, Siaya, Kenya
        • contact_details+254 724522474 / +254 700 111 395 / vnduba@gmail.com
        • contact_personDr Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2025-05-14 10:42:17
        • modified2025-05-28 15:01:56
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id832
        • application_id1542
        • sponsorNovo Nordisk A/S
        • sponsor_typeOthers
        • contact_personNadine Jabbour
        • addressNovo Allé, 2880 Bagsvaerd, Denmark
        • telephone_number+45-34486032
        • fax_numberN/A
        • cell_number+45-34486032
        • email_addressNDJO@novonordisk.com
        • created2025-05-14 10:42:17
        • modified2025-05-28 15:01:56
  • 2(array)
    • Application(array)
      • id1470
      • user_id927
      • trial_status_id(null)
      • abstract_of_study<p>\n Introduction:</p>\n<div>\n  </div>\n<div>\n Valvular heart disease is linked to significant morbidity and mortality, often necessitating surgery to replace damaged heart valves with mechanical or bioprosthetic valves. Mechanical valves are preferred for their durability, but they require lifelong anticoagulant therapy with vitamin K antagonists as the only approved treatment. Maintaining correct INR levels is crucial, as bleeding in this group has been associated with poorer prognosis. This trial aims to evaluate the safety and efficacy of maintaining a lower INR level between 1.5 and 2.5.</div>\n<div>\n  </div>\n<div>\n Study Setting: This study will enroll approximately 2,625 participants across 30 to 50 sites globally.</div>\n<div>\n  </div>\n<div>\n Study Design:</div>\n<div>\n  </div>\n<div>\n This is a prospective, randomized, open-label, blinded end-point (PROBE), multicenter clinical trial. The intervention of interest is a low INR target range (1.5 to 2.5) compared to the current guideline-recommended practice.</div>\n<div>\n  </div>\n<div>\n Expected Results:</div>\n<div>\n  </div>\n<div>\n Previous studies suggest that lower INR targets may reduce the risk of bleeding while maintaining protection against thromboembolic events. We expect to obtain similar results.</div>\n
      • study_title<p>\n A Low INR to Minimize bleeding with mechanical valves Trial (LIMIT)</p>\n
      • laymans_summary<p>\n The heart has four valves: aortic, mitral, pulmonary, and tricuspid. When these valves are affected by disease, it results in valvular heart disease. This condition impacts a portion of the population, though exact numbers in Africa or Kenya are unknown. However, it's estimated to affect about 2.5% of people in high-income countries. Valvular heart disease can range from mild to severe. Mild cases are often managed with medication, but as symptoms worsen, the disease is categorized as moderate or severe. Severe symptomatic valve disease typically requires surgical intervention.</p>\n<div>\n  </div>\n<div>\n Mechanical heart valves are commonly used devices for treating severe valve disease. Patients with mechanical heart valves need blood thinners to prevent clot formation. Warfarin is the most commonly used blood thinner, and it works by interfering with Vitamin K. To ensure the correct level of blood thinning, a test called the INR (international normalized ratio) is used. Maintaining the INR within a specific range is crucial: insufficient thinning can lead to clots, while excessive thinning can cause bleeding. For patients with mechanical aortic valves, the recommended INR range is often between 2.5 and 3.5, which comes with an increased risk of bleeding. Lowering the INR target range could potentially prevent blood clots while reducing the risk of bleeding.</div>\n<div>\n  </div>\n<div>\n Our study aims to determine if maintaining a lower INR range (1.5 to 2.5) is as safe and effective as the current guidelines in preventing blood clots and reducing bleeding in people with a mechanical aortic valve. Approximately 30 to 50 centers will participate in this study, enrolling a total of 2,625 participants. The Karen Hospital will recruit participants from our satellite clinics, the main hospital, and through medical camps. Participants will be randomly assigned to either the lower INR target group (1.5 to 2.5) or the current practice group. Eligible participants must be at least 18 years old, have a bileaflet mechanical heart valve implant in the aortic position at least 3 months prior, and must provide written informed consent. Those who plan to become pregnant, are pregnant, have another mechanical valve, or have a planned INR level less than 2 will not be enrolled.</div>\n<div>\n  </div>\n<div>\n Although participants and the study team will know the assigned groups, professionals reviewing safety information, such as bleeding or clotting incidents, will remain unaware of the groups. All participants will be followed up during routine clinic visits, with at least 10 INR tests conducted each year. Follow-up visits will monitor for illnesses and assess overall well-being, continuing until 131 clot-related events have occurred.</div>\n<div>\n  </div>\n<div>\n Participation in the study is voluntary, and participants can withdraw at any time. All participants will be closely monitored and treated if they experience any side effects or health issues, regardless of their group.</div>\n<div>\n  </div>\n
      • short_titleLIMIT
      • protocol_noECCT/25/04/04
      • version_no9.0
      • date_of_protocol14-06-2023
      • study_drugWarfarin
      • disease_conditionmechanical bileaflet valve in the aortic valve position
      • 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_namewarfarin
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressresource.center@karenhospital.org
      • 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_applicant+254700535280
      • declaration_date124-04-2025
      • declaration_principal_investigatorDr Anthony Gikonyo - Principal Investigator
      • declaration_date224-04-2025
      • placebo_presentNo
      • study_objectives<p style=\"margin: 4px 0px; font-stretch: normal; font-size: 16px; line-height: normal; font-family: Helvetica; font-size-adjust: none; font-kerning: auto; font-variant-alternates: normal; font-variant-ligatures: normal; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-position: normal; font-feature-settings: normal; font-optical-sizing: auto; font-variation-settings: normal; color: rgb(0, 0, 0);\">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">The objectives are to evaluate the safety and efficacy of a common, lower INR target range in patients with bileaflet aortic mechanical valves.</span></span></p>\n
      • principal_inclusion_criteria<p>\n <span style=\"font-size:11px;\"><span style=\"font-family:comic sans ms,cursive;\">For inclusion in the study, patients must fulfil the following requirements:</span></span></p>\n<ol>\n <li>\n <span style=\"font-size:11px;\"><span style=\"font-family:comic sans ms,cursive;\">Have had a bi-leaflet mechanical heart valve implant in the aortic position ≥ 3 months ago</span></span></li>\n <li>\n <span style=\"font-size:11px;\"><span style=\"font-family:comic sans ms,cursive;\">Be ≥18 years of age at the time of enrolment.</span></span></li>\n <li>\n <span style=\"font-size:11px;\"><span style=\"font-family:comic sans ms,cursive;\">Provide written informed consent (either from the patient or a substitute decision-maker)</span></span></li>\n</ol>\n<div>\n  </div>\n<div>\n <span style=\"font-size:11px;\"><span style=\"font-family:comic sans ms,cursive;\"><span style=\"color: rgb(0, 0, 0);\">NB: Patients on aspirin (ASA) or with additional thrombotic risk factors (e.g., atrial fibrillation will not be excluded</span></span></span></div>\n
      • principal_exclusion_criteria<p>\n <span style=\"font-family:comic sans ms,cursive;\"><span style=\"font-size:12px;\"><span new=\"\" times=\"\">Patients will be excluded if they meet any of the following criteria: </span></span></span></p>\n<ol>\n <li>\n <span style=\"font-family:comic sans ms,cursive;\"><span style=\"font-size:12px;\">Have a second implanted mechanical valve (any position)</span></span></li>\n <li>\n <span style=\"font-family:comic sans ms,cursive;\"><span style=\"font-size:12px;\">Lower boundary of planned INR range is less than 2.0</span></span></li>\n <li>\n <span style=\"font-family:comic sans ms,cursive;\"><span style=\"font-size:12px;\">Pregnant or expecting to become pregnant during the study follow-up</span></span></li>\n</ol>\n
      • primary_end_points<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">The primary outcomes are thrombosis/thromboembolism (composite of ischemic stroke, systemic thromboembolism, valve thrombosis) and major bleeding.</span></span></p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specifyA prospective, randomized, open-label, blinded end-point (PROBE), multicenter\nclinical trial. The intervention of interest is a low INR target range (1.5 to 2.5)\ncompared to the current practice as per guideline recommendations.
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Study staff:</p>\n<p>\n Principal investigator - Dr Anthony Gikonyo (Cardiologist)</p>\n<p>\n Co-Investigator- Dr Stephen Omondi Otieno(Cardiologist)</p>\n<p>\n Pharmacist - Dr Jane Njama (Pharmacist)</p>\n<p>\n Study nurse - Maureen Keire Orina - Diploma in nursing (Kenya registered nurse)</p>\n<p>\n Study nurse - Linda Karimi - Diploma in nursing (Kenya registered nurse)</p>\n<p>\n Study coordinator - Duncan Luvayo - Diploma in information science</p>\n<p>\n Study coordinator assistant- Cindy Njeri - Bachelors in economics</p>\n<p>\n Quality Assurance - Asha Mwangi - Bachelors in health communication and development</p>\n<p>\n Lab tech - Kelvin Wafula - Diploma in medical lab science</p>\n<p>\n  </p>\n<p>\n Hospital Overview:</p>\n<div>\n  </div>\n<div>\n The Karen Hospital is a tertiary-level facility located along Lang'ata Road in Nairobi. It has a capacity of 100 beds and is equipped with an Accident & Emergency (A&E) department, High Dependency Unit (HDU), and Intensive Care Unit (ICU). The hospital also features a cath lab, multiple operating theatres, and a dedicated research section. </div>\n<div>\n  </div>\n<div>\n The research area includes three research rooms, a triage/nursing room, a procedure and recovery room, and a comfortable waiting area. Additionally, it has an onsite storage facility and an offsite archive for secure data management. The hospital is supported by an ISO-certified laboratory and a fully functional pharmacy.</div>\n<div>\n  </div>\n
      • other_details_explanation<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\"> LIMIT is a multicentre study that is actively recruiting in Canada, Belgium, Spain, The Netherlands, Brazil, and China. The trial is expanding in Kenya to provide a representative sample of patient population.</span></span></p>\n
      • other_details_regulatory_notapproved<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">Approval by regulators have been granted in the UK, Spain, the Netherlands, Belgium, Brazil and Saudi Arabia.</span></span></p>\n
      • other_details_regulatory_approved<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\"><b font-size:=\"\" helvetica=\"\" style=\"color: rgba(0, 0, 0, 0.85); font-family: \">KEMRI ERC, Kenya, 1 site</b></span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   The Karen Hospital approved on September 3, 2024</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n  </p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\"><b>HiREB (Hamilton Integrated Research Ethics Board), Ontario, Canada, 3 sites</b></span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   Hamilton General Hospital initially approved August 13, 2019</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   London Health Sciences Centre initially approved April 5, 2023</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   The Ottawa Hospital initially approved August 30, 2024</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n  </p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\"><b>Quebec, Canada, 1 site</b></span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">The Jewish General initially approved February 20, 2020</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n  </p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\"><b>CONEP, Brazil, 5 sites</b></span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   INCOR initially approved 2023-01-22</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   HEW Cardiologia initially approved 2024-02-07</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   Instituto de Cardiologia e Transplantes do Distrito Federal initially approved 2023-12-12</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\"> Sociedade Hospitalar Angelina Caron initially approved 2023-11-28</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   Dante Pazzanese Institute of Cardiology initially approved 2023-10-30</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n  </p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\"><b>UZ/KU Leuven Ethics Committee, Belgium, 2 sites</b></span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   UZ Leuven initially approved 2023-09-06</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   Ziekenhuis Oost-Limburg initially approved 2024-03-28</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n  </p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\"><b>Fuwai Hospital, CAMS & PUMC ethics committee, China, 1 site</b></span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   Fuwai Hospital, CAMS & PUMC initially approved 2023-10-31</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n  </p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\"><b>Erasmus METC, Netherlands, 1 site</b></span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   Erasmus University Medical Center initially approved 2021-12-14</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n  </p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\"><b>Research Ethics Committee KFSH&RC, Saudi Arabia, 1 site</b></span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   King Faisal Specialist Hospital & Research Centre initially approved 2023-11-21</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n  </p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\"><b>Hospital de la Santa Creu i Sant Pau Ethics Committee, Spain, 1 site</b></span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   Hospital de la Santa Creu i Sant Pau initially approved 2021-07-20</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n  </p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\"><b>E. Meshalkin National Medical Research Center Ethics Committee, Russia, 1 site</b></span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">   E. Meshalkin National Medical Research Center initially approved 2019-12-26</span></span></p>\n
      • other_details_regulatory_rejected<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">MHRA in UK initially approved 2024-05-31</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">AEMPs in Spain initially approved 2021-03-09</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">CCMO in Netherlands initially approved 2021-12-14</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">FAMHP in Belgium initially approved 2021-08-02</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">Saudi FDA in Saudi Arabia initially approved 2024-02-04</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">CONEP in Brazil initially approved 2023-10-25</span></span></p>\n<p color:=\"\" font-feature-settings:=\"\" font-kerning:=\"\" font-optical-sizing:=\"\" font-size-adjust:=\"\" font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-ligatures:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" font-variation-settings:=\"\" helvetica=\"\" style=\"margin: 0px; font-stretch: normal; font-size: 13px; line-height: normal; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:comic sans ms,cursive;\">None have been rejected, nor halted by other Regulatory Authorities.</span></span></p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration3 yrs
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorINR target 2-3
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaThe Karen Hospital
      • single_site_physical_addressLangata Road, Nairobi
      • single_site_contact_personDr Anthony Gikonyo
      • single_site_telephone+254700535280
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states50
      • number_of_sites
      • multi_country_listCanada, Belgium, Brazil,\nChina, the Netherlands, Saudi\nArabia, Spain, Russia,\nCameroon, Pakistan, the UK,\nKenya, South Korea, Nepal,\nItaly, Germany, Denmark,\nBotswana, Australia,\nArgentina
      • data_monitoring_committeeYes
      • total_enrolment_per_site20 in the one site (The Karen Hospital)
      • total_participants_worldwide20
      • 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_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • 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_nameAnthony
      • investigator1_middle_nameKibuka
      • investigator1_family_nameGikonyo
      • investigator1_qualificationCardiologist
      • investigator1_professional_addressThe Karen Hospital Langata Road
      • investigator1_telephone+254700535280
      • investigator1_emailanthony.gikonyo@karenhospital.org
      • organisations_transferred_No
      • number_participants20
      • notification<p>\n 1. Kindly submit professional indemnity cover for the pharmacist; Jane Mnjama</p>\n<p style=\"margin-left:18.0pt;\">\n <strong>Karen Site Response:</strong> Dr Jane Mjama is indemnified under Karen Hospital. A copy of the institutions indemnity certificate has been included in this package.</p>\n<p>\n <strong>2. Clinical Trial Agreement-</strong>The copy of the CTA submitted is duly noted. However, we note that Dr. Stephen Omondi is listed as the investigator yet there was a change in PI to Dr. Gikonyo, kindly clarify and amend accordingly.</p>\n<p style=\"margin-left:18.0pt;\">\n <strong>Karen Site Response:</strong> The CTA with the updated PI details is undergoing changes led by the sponsor and the current PI. This will be provided within the earliest convinience upon its finalization.</p>\n<p style=\"margin-left:18.0pt;\">\n  </p>\n<p>\n  </p>\n
      • approval_date12-11-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted15-07-2025
      • is_child0
      • unsubmitted1
      • initial_date_submitted24-04-2025
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-11-12 16:07:18
      • created2024-09-09 12:09:03
      • total_sites1
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1159
        • application_id1470
        • given_nameAnthony
        • middle_nameKIBUKA
        • family_nameGikonyo
        • qualificationCardiologist
        • professional_addressThe Karen Hospital Langata Road
        • telephone+254700535280
        • emailanthony.gikonyo@karenhospital.org
        • created2024-09-10 09:23:27
        • modified2025-07-15 14:15:45
    • SiteDetail(array)
      • 0(array)
        • id1786
        • application_id1470
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2024-09-10 09:23:27
        • modified2025-07-15 14:15:45
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id781
        • application_id1470
        • sponsorLIMIT Project Office, Population Health Research Institute
        • sponsor_typeResearch Institution
        • contact_personEmilie Belley-Cote
        • address237 Barton Street East, Hamilton, Ontario, Canada L8L 2X2
        • telephone_number(905) 521-2100
        • fax_number
        • cell_number(905) 521-2100
        • email_addressLIMIT@PHRI.ca
        • created2024-09-10 09:23:27
        • modified2025-07-15 14:15:45
  • 3(array)
    • Application(array)
      • id1125
      • user_id729
      • trial_status_id7
      • abstract_of_study<p>\n Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that emerged in the human population in Wuhan City, Hubei Province, China in December 2019. As of Jan 2022, there are over 328 million SARS-CoV-2 case worldwide and over 5.54 million deaths as a result of infection with SARS-CoV-2 (COVID-19). According to WHO Situation Report on 17 January 2022, Africa has 7 million confirmed cases with over 160, 804 deaths. The COVID-19 pandemic has caused global suffering, mortality, and severe economic pressures. There is thus a continued urgent global need to develop effective and safe vaccines and drugs to make them available at scale and equitably across all countries including in Africa.</p>\n<p>\n Despite the rapid successes in vaccine development and issuance of WHO Emergency Use Listings (EUL), the WHO SAGE Interim Reports and FDA Emergency Use Authorization (EUA) for COVID-19 vaccine evaluations have reported limitations on safety and efficacy data in certain populations including children and adolescents, pregnant women, and immunocompromised individuals such as those with HIV/AIDS who are at higher risk of severe COVID-19 disease. Africa is especially vulnerable in this respect given the high prevalence of HIV/AIDS in countries such as Kenya where the prevalence is over 20% in some places.</p>\n<p>\n The risk of recurring new waves of COVID-19 cases caused by Variants of Concern (VOC) exacerbate global public health crisis. A weak immune response to either single or two doses of primary vaccination against SARS-CoV-2 has been observed in immunocompromised population. Emerging data from observational studies consistently show waning immunity to primary vaccination for SARS-CoV-2 mutants, and a decline in vaccine effectiveness against SARS-CoV-2 infection and COVID-19 with time since primary vaccinations. These factors have led to consideration of the potential need for, and optimal timing of, booster doses for vaccinated populations. However, vaccine inequality, lack of availability of the same vaccine product used for primary vaccinations and unpredictable vaccine supply remain a challenge in LMIC. Consideration of heterologous COVID-19 vaccine to allow interchangeability (mix and match) use of vaccine products available in LMIC would therefore allow for programmatic flexibility.</p>\n<p>\n Based on a recent systematic review and meta-regression analysis, across the four WHO EUL COVID-19 vaccines with the most data (i.e., BNT162b2, mRNA 1273, Ad26.COV2.S and ChAdOx1-S [recombinant] vaccine), vaccine effectiveness against severe COVID-19 decreased by about 8% (95% confidence interval (CI): 4-15%) over a period of 6 months in all age groups. In adults above 50 years, vaccine effectiveness against severe disease decreased by about 10% (95% CI: 6 – 15%) over the same period. Vaccine effectiveness against symptomatic disease decreased by 32% (95% CI: 11 – 69%) for those above 50 years of age. For some inactivated vaccines (CoronaVac and COVID-19 vaccine BIBP), WHO has already issued the recommendation for the administration of an additional dose to those aged 60 years or older as part of the primary series to make initial immunity more robust.</p>\n<p>\n The FDA issued a EUA for the Janssen Ad26.COV.S1 COVID-19 vaccine for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older. In September 2021, both the single dose and 2 dose Janssen COVID-19 vaccine regimens demonstrated high efficacy (79% protection (CI, 77%-80%) for COVID-19-related infections and 81 percent (CI, 79%-84%) for COVID-19-related hospitalizations. vs 94% (CI, 58%-100%) protection against symptomatic COVID-19 in the U.S. respectively. Furthermore, the safety profile of the vaccine remained consistent and generally well-tolerated in the 2 regimens. Finally, when a booster of the Janssen COVID-19 vaccine given 6 months after the single shot, antibody levels increased nine-fold one week after the booster and continued to climb to 12-fold higher four weeks after the booster.</p>\n<p>\n On June 14, 2021, Novavax reported the results of its PREVENT-19 pivotal Phase 3 trial of the NVX-CoV2373. The results showed an overall vaccine efficacy of 90.4% (95% CI: 82.9 – 94.6) in the US and Mexico. Sequenced data showed a vaccine efficacy was 93.2% (95% CI: 83.9 – 97.1) against Variants of Concern and Variants of Interest which represented 82% of cases. Studies of NVX-CoV2373 with Matrix-M adjuvant have demonstrated an acceptable safety and reactogenicity profile in adults ≥18 years of age. On December 20, 2021, the WHO issued interim recommendations and authorized under its emergency use listing (EUL) procedure, the NVX-CoV2373 COVID-19 vaccine developed by Novavax and Serum Institute of India.</p>\n<p>\n The FDA and WHO have both recommended continued evaluation of vaccine effectiveness following issuance of a EUA and/or licensure which is critical to address the existing uncertainties, with high urgency to understand homologous and heterologous boosting, both for improved coverage of variants of concern and due to limitations of global vaccine availability. The VIBRI Consortium proposes to carry out a Multi-Centre Phase 2b RCT to evaluate the Safety and Immunogenicity of the Janssen Ad26COVS1 and the Novavax NVX-CoV2373 used as homologous and heterologous boost strategies among HIV positive adolescents and adults with a small control arm of HIV (-) participants. The trial will enroll about 300 HIV(+) adolescents 12-17 years and about 1,650 adults aged 12 to 64 years, who have completed a primary series with a homologous vaccine series based on any one platform of a) mRNA (Moderna or Pfizer), b) adenovirus 26 (J&J) or c) inactivated (Sinopharm). These three have been the main vaccine platforms introduced across the three participating countries (Kenya, Democratic Republic of Congo and Rwanda) as of the current protocol. Participants must have completed the primary series 3-6 months prior to enrollment.</p>\n<p>\n Given the difference in vaccine rollout between countries, the timing of enrollment within each country is expected to stagger. All participants will be randomized 1:1 within their primary vaccine platform to receive either a single dose of either Janssen Ad26COVS1 vaccine or Novavax NVX-CoV2373 COVID-19 vaccine between 5 and 7 months from completion of their primary series. Due to the uncertainty of vaccine supply and to allow for adequate capture of participants, the pre-booster vaccination enrollment period may vary anywhere from -85 days to 0 days till the time of boost (Day 0).</p>\n
      • study_title<p>\n A Multi-Centre, Randomized, Double Blind, Phase 2b Trial to Evaluate the Safety and Immunogenicity of Janssen Ad26COVS1 and Novavax NVX-CoV2373 COVID-19 vaccines for Homologous and Heterologous Boosting in Adolescents and Adults Aged 12 to 64 Years with and without HIV infection in 3 African Countries (Kenya, Democratic Republic of Congo, and Rwanda).</p>\n
      • laymans_summary<p>\n COVID-19 is a worldwide disease that emerged in the human population in Wuhan, China in December 2019. As of January 2022, there were over 328 million cases worldwide and over 5.54 million deaths as a result of the infection. According to WHO Situation Report obtained 17 January 2022, Africa has 7 million confirmed cases with over 160, 804 deaths. The worldwide disease (pandemic) has caused global suffering, mortality, and severe economic pressures, hence the urgent global need to develop effective and safe vaccines and drugs to make them available at scale and equitably across all countries. Despite the rapid successes in vaccine development, the World Health Organization and US Food and Drug Administration (FDA) have reported that the COVID-19 vaccines require additional information that was not available from the big vaccine studies. Africa has a high burden of HIV with Kenya having about 5% of the population infected and in some counties in Western Kenya reporting as high as 20% of the population according to the National AIDS and STI Control Programme (NASCOP) in 2020.</p>\n<p>\n Emerging variants of concern such as Delta and Omicron, have led to new waves of COVID-19 cases worldwide and caused public health problems. Studies suggest that some individuals, especially those with poor immunity, who received either a single dose or two doses of primary vaccination against COVID-19, developed only a weak immune response to the disease. However, other studies have shown reducing immunity to primary vaccination against new cases, and a declining vaccine effectiveness against COVID-19 from about 6 months after primary vaccinations. These factors have led to consideration of the need for booster doses for vaccinated populations.</p>\n<p>\n A few studies have shown that some of the WHO approved COVID-19 vaccines are more effective when a mix and match primary and boosting schedules is used, by reducing in the number of severe COVID-19 disease and hospital admissions. Studies are currently being done on emerging COVID-19 variants, vaccine constraints, and the need to achieve a broad immune response based on mix and match boosting strategies. There is need for additional studies to assess how effective the vaccines are in the context of heterologous boost in populations with low immunity in order to address existing gaps in medical information.</p>\n<p>\n The Victoria Biomedical Research Institute (VIBRI) in Kenya, together with research partners from Kenya, Rwanda and the Democratic Republic of Congo plan to conduct a vaccine study in these countries to assess safety, and immune responses seen when a mix and match booster vaccination schedule is given to participants, how long the immune responses last after the booster and monitoring for new COVID-19 cases after vaccination. The study is important because it addresses the need for more people to access COVID-19 vaccines and make it more equal and also protects our population from shortage of vaccine supplies.</p>\n
      • short_titleVIBRI COVID-19-001/2021
      • protocol_noECCT/22/03/04
      • version_no2.0
      • date_of_protocol28-02-2022
      • study_drugJanssen Ad26COVS1 and Novavax NVX-CoV2373
      • disease_conditionCOVID-19
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameJanssen Ad.26COV2.S1 and Novavax NVX-CoV2373 in the HIV negative participants.
      • comparator_registeredJanssen Ad.26COV2.S1
      • comparator_countriesJanssen Ad.26COV2.S1is registered in over 126 countries including Kenya, South Africa, Ghana,European Union, USA, Canada, united Kingdom, Uganda, Tanzania 1. Afghanistan\n2. Andorra\n3. Argentina\n4. Bahamas\n5. Bahrain \n6. Bangladesh \n7. Benin\n8. Bolivia\n9. Botswana\n10. Brazil\n11. Brunei\n12. Burkina Faso\n13. Cambodia\n14. Cameroon\n15. Central African Republic\n16. Chile\n17. Colombia\n18. Congo-Kinshasa\n19. Djibouti\n20. Egypt\n21. Eswatini\n22. Ethiopia\n23. Gabon\n24. Ghana\n25. Guinea\n26. Honduras\n27. India\n28. Indonesia\n29. Iran\n30. Ivory Coast\n31. Jordan\n32. Kenya\n33. Kuwait\n34. Laos\n35. Lesotho\n36. Liberia\n37. Libya\n38. Madagascar\n39. Malawi\n40. Malaysia\n41. Maldives\n42. Mali\n43. Marshall Islands\n44. Mauritania\n45. Mexico \n46. Micronesia\n47. Moldova\n48. Morocco\n49. Mozambique\n50. Namibia\n51. Nepal\n52. New Zealand\n53. Nicaragua\n54. Nigeria\n55. Palau\n56. Palestine\n57. Papua New Guinea\n58. Peru\n59. Philippines\n60. Qatar\n61. Rwanda\n62. Saudi Arabia\n63. Senegal\n64. Singapore\n65. Somalia\n66. South Africa\n67. South Korea\n68. South Sudan\n69. Sudan\n70. Syria\n71. Taiwan \n72. Tanzania\n73. Thailand\n74. Tunisia\n75. Uganda\n76. Ukraine\n77. United Kingdom\n78. United States \n79. Vietnam \n80. Yemen\n81. Zambia \n82. Zimbabwe\nEMA countries \n1. Austria\n2. Belgium\n3. Bulgaria\n4. Croatia\n5. Cyprus\n6. Czech Republic\n7. Denmark\n8. Estonia\n9. Finland\n10. France\n11. Germany\n12. Greece\n13. Hungary\n14. Iceland\n15. Ireland\n16. Italy\n17. Latvia\n18. Liechtenstein\n19. Lithuania\n20. Luxembourg\n21. Malta\n22. Netherlands\n23. Norway\n24. Poland\n25. Portugal\n26. Romania\n27. Slovakia\n28. Slovenia\n29. Spain\n30. Sweden\nCARPHA countries\n1. Antigua and Barbuda\n2. Bahamas\n3. Barbados\n4. Belize\n5. Dominica\n6. Grenada\n7. Guyana\n8. Haiti\n9. Jamaica\n10. Saint Kitts and Nevis\n11. Saint Lucia\n12. Saint Vincent and the Grenadines\n13. Suriname\n14. Trinidad and Tobago\n\nNon-country entities \n• American Samoa\n• Anguilla\n• Aruba\n• Bermuda\n• British Virgin Islands\n• Caribbean Netherlands\n• Cayman Islands\n• Curaçao\n• French Polynesia\n• Greenland\n• Guam\n• Montserrat\n• New Caledonia\n• Northern Cyprus\n• Northern Mariana Islands\n• Puerto Rico\n• Sint Maarten\n• Turks and Caicos Islands\n\n\n\n.Novavax NVX-CoV2373 is registered in over 36 coutries e.g. • India \n• Indonesia \n• New Zealand \n• Philippines \n• Singapore\n• United Kingdom\n\n• Austria \n• Belgium \n• Bulgaria \n• Croatia \n• Cyprus \n• Czech Republic \n• Denmark \n• Estonia \n• Finland \n• France \n• Germany \n• Greece\n• Hungary \n• Iceland \n• Ireland \n• Italy \n• Latvia \n• Liechtenstein \n• Lithuania \n• Luxembourg \n• Malta \n• Netherlands \n• Norway \n• Poland\n• Portugal \n• Romania \n• Slovakia \n• Slovenia \n• Spain \n• Sweden\n• Hong Kong \n• Palau \n• Panama \n• St. Kitts and Nevis \n• St. Lucia\n• St. Vincent and the Grenadines \n• Switzerland \n• Turkey \n• United Arab Emirates \n• United States\n
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressi.omollo13@gmail.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_applicantDr Lucas Otieno Tina
      • declaration_date111-03-2022
      • declaration_principal_investigatorPrincipal Investigator
      • declaration_date211-03-2022
      • placebo_presentNo
      • study_objectives<p>\n <strong>Primary safety Objectives</strong></p>\n<p>\n 1. To evaluate reactogenicity (solicited adverse events (AEs) Ad26.COV2S1 and NVX-CoV2372 following boosting. 2. To evaluate Serious Adverse events related to vaccination of Ad26.COV2S1 or NVX-CoV2372 during the entire study.</p>\n<p>\n <strong>Primary Immunogenicity Objectives</strong></p>\n<p>\n To evaluate the immunogenicity of Ad26.COV2S1 and NVX-CoV2372 vaccines at day 28.</p>\n<p>\n <strong>Secondary safety Objectives</strong></p>\n<p>\n 1.To evaluate all unsolicited AEs post-vaccination through 28 days and treatment emergent adverse events through 85 days in all participants. 2.To evaluate safety in terms of adverse events of special interest (AESIs) following vaccination, for HIV (+) participants through end of study. 3.To describe severe adverse events through end of study in all participants.</p>\n<p>\n <strong>Secondary Immunogenicity Objectives</strong></p>\n<p>\n 1.To compare the immunogenicity of heterologous boost in participants at Day 28 (IgG ELISA and neutralization). 2.To compare the durability of response through end of study (IgG ELISA and neutralization). 3.To evaluate mucosal immunogenicity of heterologous boost in participants at Day 28 (S-IgA ELISA). Exploratory Objectives 1.To evaluate the occurrence SARS-CoV-2 variants of concern in HIV (+) participants with moderate to severe disease following boosting vaccination. 2.To evaluate the Cell Mediated Immune response of Ad26.COV2S1 and NVX-CoV2372 vaccines in adults HIV (+) and HIV (-) participants. 3.To demonstrate the continued efficacy of either vaccine (Ad26.COV2S1 or NVX-CoV2372), when given in a heterologous boost setting, in the prevention of SARS-CoV-2 infection in HIV (+) and HIV (-) participants. 4.To identify a threshold of immune protection for HIV (+) and HIV (-) participants to prevent SARS-CoV-2 following vaccination.</p>\n
      • principal_inclusion_criteria<p>\n <strong>Inclusion Criteria To be eligible for the study, each HIV (+) participants must satisfy all of the following criteria:</strong></p>\n<p>\n 1. Adolescent male or female aged ≥ 12 to 17 years at screening and adult male or female aged ≥ 18 to 64 years at screening (inclusive).</p>\n<p>\n 2. Written informed consent (and assent if adolescent), after review of the consent form and having adequate opportunity to discuss the study with an investigator or a qualified designee. For participants who cannot read or write, the consent must be witnessed by a literate third party not involved in study conduct.</p>\n<p>\n 3. Comply with study procedures, including potential home visits for COVID-19 follow-up.</p>\n<p>\n 4. Has completed a primary homologous vaccination series at least 3 months but no more than 6 months prior to enrollment. Vaccinations allowed include:</p>\n<p>\n a) mRNA (Moderna mRNA-1273 or Pfizer/BNT) – primary series is 2 doses</p>\n<p>\n b) Adenovector 26 (Janssen Ad26COVS1) – primary series is 1 dose;</p>\n<p>\n c) Inactivated whole virus (Sinopharm-BIBP) – primary series is 2 doses;</p>\n<p>\n 5. Female participants of childbearing potential (defined as any female who has experienced menarche and who is NOT surgically sterile [i.e, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months or documented plasma follicle-stimulating hormone level ≥40 mIU/mL]) must agree to consistently use an effective method of contraception from enrolment and agree to continue adequate contraception until 12 weeks after vaccination:</p>\n<p>\n a. Condoms (male or female)</p>\n<p>\n b. Diaphragm with spermicide</p>\n<p>\n c. Cervical cap with spermicide</p>\n<p>\n d. Intrauterine device</p>\n<p>\n e. Oral or patch contraceptives</p>\n<p>\n f. Hormonal Contraceptives implants or injection e.g., Norplant®, Depo-Provera®.</p>\n<p>\n g. Abstinence, as a form of contraception, is acceptable if in line with the participant’s lifestyle.</p>\n<p>\n NOTE: Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. These procedures and laboratory test results must be confirmed by physical examination, by participant recall of specific date and hospital/facility of procedure, or by medical documentation of said procedure.</p>\n<p>\n 6. Medically stable at screening, as determined by the investigator (based on review of health status, vital signs, medical history, and targeted physical examination). Acceptable Vital signs as determined by the Principal Investigator or designee.</p>\n<p>\n 7. Receiving highly active antiretroviral therapy (HAART) and using the same regimen the past 8 weeks before screening. Changes in antiretroviral dosage within 8 weeks prior to entering the study are permitted. In addition, the exchange of pharmacological formulation (e.g., the conventional formulation for combination formulations) is allowed. If regimen has changed then the participant can be reconsidered for inclusion once the 8 weeks has passed.</p>\n<p>\n 8. An HIV-1 viral load < 1000 copies/mL and/or CD4 Count ≥ 200 cells/mm3 within 3 months before randomization. May be taken during screening or utilize medical testing from clinic.</p>\n<p>\n 9. Documentation of HIV positivity by HIV rapid test or assay as per the Ministry of Health guidelines in the respective countries. Each HIV (-) participant must meet all the following criteria to be enrolled in this study:</p>\n<p>\n 1. Male or female aged ≥ 18 to 64 years at screening, inclusive.</p>\n<p>\n 2. Willing and able to give informed consent prior to study enrolment and comply with study procedures, including potential home visits for COVID-19 follow-up. 3. Has completed a primary homologous vaccination series at least 3 months but no more than 6 months prior to enrollment. Vaccinations allowed include:</p>\n<p>\n a. mRNA (Moderna mRNA-1273 or Pfizer/BNT) – primary series is 2 doses</p>\n<p>\n b. Adenovector 26 (Janssen Ad26COVS1) – primary series is 1 dose;</p>\n<p>\n c. Inactivated whole virus (Sinopharm-BIBP) – primary series is 2 doses;</p>\n<p>\n 4. Female participants of childbearing potential (defined as any female who has experienced menarche and who is NOT surgically sterile [i.e, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months or documented plasma follicle-stimulating hormone level ≥40 mIU/mL]) must agree to abstain from enrolment and through 6 months after the last vaccination OR agree to consistently use an effective method of contraception from enrolment and through 6 months after the last vaccination:</p>\n<p>\n a. Condoms (male or female)</p>\n<p>\n b. Diaphragm with spermicide</p>\n<p>\n c. Cervical cap with spermicide</p>\n<p>\n d. Intrauterine device</p>\n<p>\n e. Oral or patch contraceptives</p>\n<p>\n f. Hormonal Contraceptives implants or injection e.g., Norplant®, Depo-Provera®.</p>\n<p>\n g. Abstinence, as a form of contraception, is acceptable if in line with the participant’s lifestyle.</p>\n<p>\n NOTE: Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. These procedures and laboratory test results must be confirmed by physical examination, by participant recall of specific date and hospital/facility of procedure, or by medical documentation of said procedure.</p>\n<p>\n 5. Medically stable at screening, as determined by the investigator (based on review of health status, vital signs, medical history, and targeted physical examination). Acceptable vital signs by PI.</p>\n<p>\n 6. Documentation of negative HIV rapid test (or assay) as per the Ministry of Health guidelines in the respective countries.</p>\n
      • principal_exclusion_criteria<p>\n <strong>Participants with any of the following criteria will be excluded:</strong></p>\n<p>\n 1. Use of a heterologous COVID-19 primary series at the platform level (mRNA, Adenovector and inactivated vaccine).</p>\n<p>\n 2. Use of an extended primary vaccination series or prior booster with any SARS-COV2 vaccine.</p>\n<p>\n 3. Any subject with prior Adverse Events of Special Interest Relevant to COVID-19 (see table 6).</p>\n<p>\n 4. Unstable or Severe Chronic disease inclusive of:</p>\n<p>\n a. Hypertension (elevated blood pressure [SBP>160mmHg or DBP>100mmHg]). Note that participants can be retested once after resting or return on another day for retesting. Participants may also have anti-hypertensive medication adjusted and may be reassessed after at least 2 weeks.</p>\n<p>\n b. Congestive heart failure (CHF) stage 3 or greater or diagnosed cardiovascular disease that is not controlled using medication in the past 6 months.</p>\n<p>\n c. Chronic obstructive pulmonary disease (COPD) with a history of an acute exacerbations repeated in the past 2 years. Note: If participant has been stable the last 6 months and are not Gold stage 3 or greater, they may be included.</p>\n<p>\n d. Asthma stage 4 and/or unstable cases with asthma therapy adjustments in the past that 2 months.</p>\n<p>\n e. Type 1 or any type 2 diabetes (adult onset) of severe grade by history/medical review or with an HbA1c > 8.5 in the last 6 months.</p>\n<p>\n f. Chronic kidney disease requiring dialysis or GFR <30 (may use associated creatinine based on age and gender).</p>\n<p>\n g. Chronic hepatic disease with evidence of hepatic compromise by history/medical review. Includes known Hepatitis B or C.</p>\n<p>\n h) Chronic or serious neurological diseases (e.g. cerebrovascular disease (including transient ischemic attacks), autoimmune disorders, neurologic deterioration (including dementia), Guillain Barre syndrome).</p>\n<p>\n i) Any ongoing, symptomatic acute illness requiring medical or surgical care or chronic illness of severe grade or that is not stable over the past 6 months (at the discretion of the investigator).</p>\n<p>\n j) HIV Stage III/IV</p>\n<p>\n 5. Cognitive impairment – congenital or acquired</p>\n<p>\n 6. A child in care i.e., a child who is in the custody, care or guardianship of a director or a director of adoption.</p>\n<p>\n 7. Participation in research involving an investigational product (drug/biologic/device) within 30 days prior to first study vaccination and planned participation during this study. Exception is if participant in a follow up safety phase and the investigation product has been given > 6 months previously.</p>\n<p>\n 8. Prior receipt of an Ebola vaccine i.e., Ad26.ZEBOV/MVA-BN-Filo vaccines.</p>\n<p>\n 9. Received any other vaccine within 4 weeks prior to first study vaccination or planned vaccination within 4 weeks after study vaccination (including mass vaccination campaigns). Participants may be revaluated after the window has passed.</p>\n<p>\n 10. Any autoimmune or immunodeficiency disease/condition (iatrogenic or congenital), excluding HIV. Note: Stable endocrine disorders that have a confirmed autoimmune etiology (e.g., thyroid, pancreatic), including stable diabetes are allowed.</p>\n<p>\n 11. Chronic administration (>14 continuous days) of immunosuppressant, systemic glucocorticosteroids, or other immune-modifying drugs within 60 days prior to first study vaccination, excluding HAART. Note: An immunosuppressant dose of glucocorticoid is defined as a systemic dose ≥ 10 mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted.</p>\n<p>\n 12. Received immunoglobulin, blood-derived products, or other immunosuppressant drugs within 90 days prior to first study vaccination, excluding HAART.</p>\n<p>\n 13. Known disturbance of coagulation (iatrogenic or congenital). Note: The use of low-dose aspirin (≤ 325 mg/day) as prophylaxis is acceptable in dosages consistent with local standards of care, but the use of other platelet aggregation inhibitors, thrombin inhibitors, Factor Xa inhibitors, or warfarin derivatives is exclusionary, regardless of bleeding history, because these imply treatment or prophylaxis of known cardiac or vascular disease.</p>\n<p>\n 14. Any disease or disorder that would indicate a life expectancy less than 3 years such as active cancer.</p>\n<p>\n 15. Any known allergies to products contained in the investigational product or latex allergy or any history of anaphylaxis in relation to any previous vaccination. 16. Women who are breastfeeding or who are pregnant at the time of screening or plan to become pregnant within the first 12 months of the study.</p>\n<p>\n 17. A serious adverse event that occurs between screening and randomization. Subjects will not be allowed to be randomized.</p>\n<p>\n 18. History of alcohol abuse or drug addiction within 2 years prior to the first study vaccination.</p>\n<p>\n 19. Any condition (other than HIV) that, in the opinion of the investigator, would pose a health risk to the participant if enrolled (including neurologic or psychiatric conditions deemed likely to impair the quality of safety reporting).</p>\n<p>\n 20. Study team member or first-degree relative of any study team member (inclusive of sponsor, and site personnel involved in the study).</p>\n<p>\n <strong>Temporary exclusions: </strong></p>\n<p>\n 21. Acute respiratory and/or non-respiratory illness or documented temperature of > 38°C in the past 24 hours. Note: Participant may be re-evaluated after symptoms have resolved for at least 3 days.</p>\n<p>\n 22. Positive RT-PCR SARS-CoV-2 test during screening or at time of randomization. Subject must be SARS-COV-2 symptom free and have a negative test prior to randomization. 23. Documented severe SARS-CoV-2 infection in the last 3 months. May be rescreened when this period has passed.</p>\n
      • primary_end_points<p>\n <strong>Primary safety end points:</strong></p>\n<p>\n 1. Occurrence of solicited AEs (local and systemic) reactogenicity events through 7 days following boosting vaccination. Analysis to include by HIV status, age group, booster treatment group, and heterologous vaccination series (primary platform + boosted vaccine).</p>\n<p>\n 2. Incidence of vaccine related Serious Adverse Events (SAEs) throughout the study period. Analysis to include by HIV status, age group, booster treatment group, and heterologous vaccination series (primary platform + boosted vaccine).</p>\n<p>\n <strong>Primary Immunogenicity end points: </strong></p>\n<p>\n 1. SARS-CoV-2 neutralization: SARS-CoV-2 neutralizing titers in serum measured by a virus neutralization assay (VNA) using pseudovirion expressing S protein (standardized to 50% neutralization with 95% CI).</p>\n<p>\n 2. Serum IgG antibodies to SARS-CoV-2 rS protein measured by enzyme-linked immunosorbent assay (ELISA) using geometric mean titers (GMT with 95% CI). 3. Geometric mean fold ratio over baseline (IgG and VNA). Analysis to include by HIV status, age group and booster treatment group (Ad26.COV2S1 or NVX-CoV2373)</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyImmunogenicity, prevention
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n The site is equiped to conduct clinical trials with qualified site Investigators and personnel by experience, eduaction and training. The site has emergency facilities, both clinical and laboratory equipment including adequate facilities to conduct the trials i.e.Participant wating area/Reception, vital site stations, Clinical rooms, Laboratory, Study Pharmacy, data entry room, conference room, monitoring room and administrative offices. Study site is located within the Kisumu County Referal Hospital and therfore has access to outpatient, inpatient facilities and medical personnel within the Hospital.</p>\n<p>\n Below is a list of staff names with their roles:</p>\n<p>\n <strong>Name:                    Role:</strong></p>\n<p>\n Lucas Otieno Tina- PI</p>\n<p>\n Walter Otieno- Sub-I</p>\n<p>\n Dismas Oketch- Sub-I</p>\n<p>\n Henry Nyongesa- Sub-I</p>\n<p>\n Antony Oindo- Sub-I</p>\n<p>\n Millicent Melanie- Pharmacist</p>\n<p>\n Anne Rogena -Pharmacist</p>\n<p>\n David Ogolla- Project Manager</p>\n<p>\n Geoffrey Olado- CRC</p>\n<p>\n Brenda Okuba -CRC</p>\n<p>\n Jew Ochola -Lab Manager</p>\n<p>\n Vincent Omondi- Lab Tech</p>\n<p>\n Nicakanor Odiwour -Lab Tech</p>\n<p>\n Eunice Oyola- Clinician</p>\n<p>\n Leah Martha Atieno -Clinician</p>\n<p>\n Annette Imojong Onyamasi- Nurse</p>\n<p>\n Gaudensia Oyugi Nyauke- Nurse</p>\n<p>\n Jane Atieno Oriato- Nurse</p>\n<p>\n Lydiah Otitah- Data clerk</p>\n<p>\n Franciscah Awino -Data clerk</p>\n<p>\n Alfred Ochieng Data clerk</p>\n<p>\n Fredrick Otieno- Field coordinator</p>\n<p>\n Serphine Wamboga- Field</p>\n<p>\n Edith Aluoch Field- Assistant</p>\n<p>\n Paul Osodo HTS -provider</p>\n<p>\n Sharon Omollo- Procurement</p>\n<p>\n Josephine Akinyi -Administrator</p>\n<p>\n Mary Onyango- HR</p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n 1. Rwanda FDA-Submission Feb  2022.</p>\n<p>\n 2. Directorate of Pharmacy and Medicine (Direction de la Pharmacie et du Médicament (DPM) planned for Mar 2022.</p>\n
      • other_details_regulatory_approved<p>\n Approval still pending for Rwanda and DRC</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration24 months
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparator Ad.26COV2.S1, NVX-CoV237
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaVictoria Biomedical Research Institute,
      • single_site_physical_addressKisumu Country Referal Hospital
      • single_site_contact_personDr. Lucas Otieno Tina
      • single_site_telephone+ 254 720 597654
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states2
      • number_of_sites
      • multi_country_listRwanda and Democratic Republic of Congo(DRC)
      • data_monitoring_committeeYes
      • total_enrolment_per_siteOne site participating in Kenya. 1000 participants for the participating Kenyan site.
      • total_participants_worldwide1950
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • 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_nameDr. Lucas
      • investigator1_middle_nameOtieno
      • investigator1_family_nameTina
      • investigator1_qualificationMBChB, MSc. DLSHTM
      • investigator1_professional_addressVictoria Biomedical Research Institute, Kisumu County Hospital, P.O. Box 7180-40100, Kisumu, Kenya
      • investigator1_telephone+ 254 720 597654
      • investigator1_emailItina@vibriafrica.org
      • organisations_transferred_Yes
      • number_participants1000 participants.
      • notification
      • approval_date04-05-2022
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted28-04-2022
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonComments raised by reviewers have been addressed sufficiently
      • final_report<div>\n <strong>Report Overview</strong></div>\n<div>\n This report presents an analysis of enrollment, safety, and immunogenicity data following the database lock on February 5, 2025. Key tables summarising the findings are included within the main body of the report, while additional tables and figures referenced throughout the text are provided in the appendices.</div>\n<div>\n <strong>Study Site Status</strong></div>\n<div>\n All three study sites in Kenya, DRC, and Rwanda successfully completed enrollment and follow-up for both adults and adolescents.</div>\n<div>\n <strong>Enrollment Status</strong></div>\n<div>\n • 1919 subjects (1619 adults and 300 adolescents) were enrolled in this study.</div>\n<div>\n <strong>Participant Status</strong></div>\n<div>\n • All the 1919 participants were administered with a booster vaccine.</div>\n<div>\n <strong>Pausing Rules</strong></div>\n<div>\n No pausing rules were enforced throughout the study. However, as noted in the previous DSMB meeting (1st interim analysis), one participant (01-0862) recorded a grade 4 fever (40.5°C) in the diary card following vaccination. Upon clinical evaluation at Visit 3, the participant reported no history of fever or chills after vaccination. Based on clinical judgment, this event was not considered potentially life-threatening.</div>\n<div>\n <div>\n <strong>Safety Summary</strong></div>\n <div>\n • 206/300 (69%) adolescent participants reported at least one local AE (Pfizer BNT: 105/150 (70%) and Novavax: 101/150 (67%). While 171/300 (57%) participants reported at least one systemic AE (Pfizer BNT: 87/150 (58%) and Novavax: 84/150 (56%)). Lastly, 90/300 (30%) participants reported at least one unsolicited AE (Pfizer BNT: 43/150 (29%) and Novavax: 47/150 (31%)).</div>\n <div>\n • Safety findings for booster vaccines (Pfizer BNT/Novavax) in adolescents indicate predominantly mild local and systemic adverse events (AEs), with Pfizer BNT showing a higher proportion of moderate events compared to Novavax. Local AEs, such as pain, were common, but no severe or life-threatening events occurred. Unsolicited AEs were infrequent and not life-threatening.</div>\n <div>\n • 652/1619 (40%) adult participants reported at least one local AE (Ad26.COV2S1: 365/808 (45%) and NVX-CoV2373: 287/811 (35%). While 750/1619 (46%) participants reported at least one systemic AE (Ad26.COV2S1: 388/808 (48%) and NVX-CoV2373: 362/811 (45%)). Lastly, 585/1619 (36%) participants reported at least one unsolicited AE (Ad26.COV2S1: 279/803 (35%) and NVX-CoV2373: 306/811 (38%)).</div>\n <div>\n • In adults following booster vaccines (Janssen/Novavax, mild local AEs predominated, with the Adenovector platform exhibiting more prevalence. Grade 3 and 4 events were reported in a small percentage, including pain and systemic AEs like fever and fatigue. Unsolicited AEs mirrored solicited ones, with Grade 2 events more frequent on the Adenovector platform. Severe unsolicited AEs were diverse, but none were directly linked to the vaccines.</div>\n <div>\n • Overall, 94 serious adverse events were documented among 60 participants, and none were associated with the vaccines.</div>\n <div>\n • The pooled breakthrough prevalence was relatively low at 6%.</div>\n <div>\n • Breakthrough cases among adults displayed a varied severity mix, predominantly presenting as asymptomatic or mild, in line with the vaccines' primary objective of minimising illness severity. Noteworthy, although infrequent, were instances of moderate and severe cases.</div>\n <div>\n • Temporal patterns in breakthrough infections varied among vaccine platforms. Adults vaccinated with mRNA and Adenovector platforms experienced a more extended duration before a substantial reduction in breakthrough infections, approximately extending to month 6. In contrast, breakthrough cases in adults receiving the Inactivated platform exhibited an earlier deceleration, initiating</div>\n <div>\n around month 3.</div>\n <div>\n <div>\n <strong>Immunogenicity Summary</strong></div>\n <div>\n • The analysis of ELISA results (ELU/mL, BAU/mL) and the neutralization assay (NT50/ml, IU/ml) consistently showed that both booster vaccines led to a significant increase in antibodies against SARS-CoV-2 across all three platforms, especially at Day 28.</div>\n <div>\n • Following booster vaccinations, both adolescents and adults exhibited a substantial rise in SARS-CoV-2 antibody levels at Day 28, signaling a robust increase in immune response compared to Day 0.</div>\n <div>\n • Adults showed a marked elevation in immune response at Day 28, with subsequent gradual declines, and a significant decrease at Month 12 for those who received primary vaccination with Adenovector followed by Ad26.COV2S1 booster and mRNA platform followed by both vaccines.</div>\n <div>\n • Platform-specific effects showed the inactivated platform provoking the strongest immune response. Demographic analyses revealed subtle differences, with no significant distinctions in responses among HIV+ and HIV- participants, and slight age-related variations.</div>\n <div>\n • Confirmatory results in ELISA results (ELU/mL, BAU/mL), aligned with Neutralisation assay (NT50/ml, IU/mL) findings.</div>\n <div>\n • Cell Mediated Immunity (IFN-y): Vaccine A on the Adenovector platform showed a marginal decline in cell-mediated immune response at Day 7, while Vaccine B exhibited a significant boost. On the mRNA platform, both vaccines demonstrated a substantial surge in cell-mediated immune response at Day 7.</div>\n <div>\n <div>\n <strong>Protocol Deviations</strong></div>\n <div>\n A total of 152 Protocol Deviations were reported:</div>\n <div>\n • 70 (68 in DRC and 2 in Kenya) were missed visits, lost to follow up, out of window visits.</div>\n <div>\n • 19 (10 Kenya and 9 DRC) were temperature excursions.</div>\n <div>\n • 12 (1 Kenya and 11 DRC) were related to randomisation of participants in incorrect stratification groups (now corrected).</div>\n <div>\n • 51 were due to various reasons from late reporting of SAEs, issues to do with consenting procedure (incorrect versions, missing date/signatures etc.), Reactogenicity data gathered earlier than the 30mins set time, participant being a spouse of trial staff, among others.</div>\n <div>\n • 1 was related with incorrect masking procedures at Rwanda site.</div>\n <div>\n  </div>\n </div>\n </div>\n</div>\n
      • implication_results<div>\n <strong>DISCUSSION</strong></div>\n<div>\n This study provides a comprehensive evaluation of the safety, immunogenicity, and durability of COVID-19 booster vaccinations across diverse vaccine platforms, encompassing both adolescents and adults, including individuals living with HIV. The findings generate valuable insights into vaccine reactogenicity, serious adverse events (SAEs), immune responses, and the comparative efficacy of heterologous versus homologous booster strategies. These results have significant implications for public health policies, particularly in African settings where vaccine availability, comorbidities, and the high burden of infectious diseases necessitate a tailored approach to COVID-19 booster strategies.</div>\n<div>\n  </div>\n<div>\n <strong>Safety and reactogenicity</strong></div>\n<div>\n The reactogenicity profile observed in this study aligns with prior large-scale clinical trials (Polack et al., 2020; Voysey et al., 2021). Local adverse events (AEs) were predominantly mild to moderate, with injection site pain being the most frequently reported symptom across all vaccine groups. Adolescents exhibited a higher incidence of local reactogenicity than adults, with Grade 1 and Grade 2 pain being more prevalent in the mRNA group. Redness and swelling were relatively infrequent and limited to Grade 1 severity, with only isolated cases of Grade 2 swelling. Systemic adverse events followed a similar trend, with fatigue, headache, and muscle ache being the most commonly reported symptoms. Fever incidence was low, with most cases classified as Grade 1 or 2, and only a small proportion experiencing Grade 3 fever. Notably, mRNA vaccine recipients reported higher rates of systemic reactogenicity compared to NVX-CoV2373 recipients, consistent with global findings (Munro et al., 2021).</div>\n<div>\n Among adults, local reactogenicity was comparatively lower than in adolescents, particularly among Ad26.COV2.S recipients, who exhibited the lowest rates of injection site pain. NVX-CoV2373 recipients demonstrated slightly higher local reactogenicity than Ad26.COV2.S vaccine recipients but remained within established safety parameters. Systemic AEs were less frequent in adults, with mRNA vaccine recipients reporting the highest rates of fatigue and headache, while inactivated vaccine recipients exhibited the lowest systemic AE rates.</div>\n<div>\n Serious adverse events (SAEs) were reported in approximately 3% of participants, with infections such as malaria, pneumonia, and sepsis being the primary causes of hospitalisation. Notably, none of these SAEs were directly attributed to vaccination, reinforcing the strong safety profile of the booster vaccines under investigation. These findings highlight the importance of continued pharmacovigilance, especially in regions with high endemic disease burdens (Madhi et al., 2022).</div>\n<div>\n  </div>\n<div>\n <strong>Immunogenicity of booster vaccination</strong></div>\n<div>\n Antibody responses, assessed at Day 28 post-booster administration, demonstrated significant elevations across all vaccine platforms. The GMTs for both binding and neutralising antibodies peaked at this time point, with mRNA-based boosters (Moderna/Pfizer) eliciting the highest responses, followed by NVX-CoV2373 and Ad26.COV2.S. These findings are consistent with data from the COV-BOOST study and other global immunogenicity trials (Munro et al., 2021; Feng et al., 2022). In adolescents, mRNA-based boosters yielded the highest GMR of antibody titers, reinforcing their prioritisation for this age group. NVX-CoV2373 also demonstrated strong</div>\n<div>\n immune responses in adolescents. In adults, NVX-CoV2373 exhibited superior immune responses compared to Ad26.COV2.S, with HIV-positive participants mounting immune responses comparable to their HIV-negative counterparts. These findings reaffirm the effectiveness of booster vaccination in immunocompromised populations (Madhi et al., 2022; Andrews et al., 2023).</div>\n<div>\n  </div>\n<div>\n <strong>Durability of immune responses and breakthrough infections</strong></div>\n<div>\n Although peak antibody responses were robust, immune titers began to decline by Day 85, with continued waning observed at Month 6. The most pronounced decline was observed among mRNA vaccine recipients, whereas Ad26.COV2.S recipients demonstrated more sustained antibody levels over time. These findings are consistent with global trends, where mRNA vaccines elicit strong initial responses but exhibit relatively rapid waning compared to adenovector vaccines (Bar-On et al., 2021; Falsey et al., 2022).</div>\n<div>\n Breakthrough infections were predominantly reported among adults, with higher infection rates observed in mRNA vaccine recipients. This suggests that despite robust initial immunogenicity, periodic boosting is necessary to maintain long-term protection, particularly in high-risk populations. Given that most infections occurred within six months of booster administration, an evidence-based approach to reboosting should prioritise a six-month interval, especially for immunocompromised individuals and high-risk populations. However, continued serological monitoring is essential to assess long-term immune kinetics and refine reboosting strategies accordingly.</div>\n<div>\n <strong>Heterologous vs. homologous boosting strategies</strong></div>\n<div>\n The study also assessed the comparative immunogenicity of heterologous versus homologous boosting strategies. Among adolescents, boosting with an mRNA vaccine following a primary mRNA series resulted in superior immune responses. In adults, heterologous boosting with NVX-CoV2373 yielded stronger immune responses relative to homologous boosting. These findings reinforce international recommendations advocating for heterologous booster strategies to maximise immunogenicity (Atmar et al., 2021; Munro et al., 2021).</div>\n<div>\n  </div>\n<div>\n <strong>Potential policy implications</strong></div>\n<div>\n • Strategic booster deployment: mRNA vaccines should be prioritised for adolescents due to their superior immunogenicity. For adults, NVX-CoV2373 has demonstrated robust and durable responses, making it an ideal choice, particularly for individuals living with HIV.</div>\n<div>\n • Heterologous booster strategies: Given the enhanced immune responses observed with heterologous boosting, national immunisation policies should incorporate heterologous booster regimens where feasible to optimize protection.</div>\n<div>\n • Reboosting based on immune durability and infection trends: The high incidence of infections within six months post-booster suggests that reboosting should be scheduled at six-month intervals, particularly for high-risk groups such as immunocompromised individuals and healthcare workers. However, serological monitoring should inform personalised booster schedules.</div>\n<div>\n • Enhanced pharmacovigilance and surveillance: Continuous safety monitoring is essential, especially in regions with high infectious disease burdens. Strengthening pharmacovigilance infrastructure will support early detection of adverse events and enhance vaccine confidence.</div>\n<div>\n  </div>\n<div>\n <strong>Conclusion</strong></div>\n<div>\n This study reinforces the safety, immunogenicity, and effectiveness of COVID-19 booster vaccines across diverse platforms and populations. The findings provide a strong evidence base to inform national vaccination strategies, particularly in African settings characterised by variable vaccine availability and diverse population health profiles. While all vaccines demonstrated strong initial immune responses, variations in durability underscore the need for tailored booster strategies. Continuous surveillance, data-driven reboosting schedules, and strategic public health messaging will be pivotal in sustaining immunity and ensuring long-term protection against COVID-19.</div>\n<div>\n  </div>\n<div>\n <strong>REFERENCES</strong></div>\n<div>\n Pinheiro, J.C. (2014). Linear Mixed Effects Models for Longitudinal Data. In Wiley StatsRef: Statistics Reference Online (eds N. Balakrishnan, T. Colton, B. Everitt, W. Piegorsch, F. Ruggeri and J.L. Teugels). https://doi.org/10.1002/9781118445112.stat05514</div>\n<div>\n  </div>\n
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        • given_nameDr. Lucas
        • middle_nameOtieno
        • family_nameTina
        • qualificationMBChB, MSc. DLSHTM
        • professional_addressVictoria Biomedical Research Institute, Kisumu County Hospital, P.O. Box 7180-40100, Kisumu, Kenya
        • telephone+ 254 720 597654
        • emailItina@vibriafrica.org
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        • sponsorVictoria Biomedical Research Institute
        • sponsor_typeResearch Institution
        • contact_personDr. Lucas Otieno Tina
        • addressVictoria Biomedical Research Institute, Kisumu County Referal Hospital, P.O. Box 7180-40100, Kisumu, Kenya
        • telephone_number+ 254 720 597654
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      • abstract_of_study<p>\n This study aims to evaluate PK, safety, tolerability and efficacy of a new formulation of artemether-lumefantrine dispersible tablets in neonates and infants with acute uncomplicated Plasmodium falciparum malaria.</p>\n<p>\n Malaria is a disease that has a much higher prevalence and severity in infants and children. Although relatively infrequent as compared to the number of cases in infants and children greater or equal to 5kg, confirmed malaria in neonates and infants less than 5kg does exist in certain endemic countries and calls for evaluation of appropriate treatment. It is still significant unmet medical need as there are no approved treatments for this vulnerable group of patients</p>\n
      • study_title<p>\n A multicenter, open-label, single-arm study to evaluate the PK, safety, tolerability and efficacy of a new artemether-lumefantrine (2.5 mg:30 mg) dispersible tablet in the treatment of infants and neonates <5 kg body weight with acute uncomplicated Plasmodium falciparum malaria.</p>\n<p>\n Study number: CCOA566B2307</p>\n
      • laymans_summary<p>\n  This Phase II/III study aims to evaluate Pharmacokinetics, safety, tolerability  and efficacy of a new artemether-lumefantrine dispersible tablet in infants and neonates less than 5 Kg body weight with acute uncomplicated Plasmodium falciparum malaria. This will be a multicenter, open-label, single-arm, adaptive design with dose adaptation (de-escalation and escalation_ study in infants and neonates with P. falciparum malaria.</p>\n
      • short_titleCALINA STUDY
      • protocol_noECCT/20/12/03
      • version_no00
      • date_of_protocol02-12-2019
      • study_drugCoartem®/Riamet® - Artemether:lumefantrine 2.5 mg:30 mg (COA566 2.5 mg:30 mg)
      • disease_conditionPlasmodium falciparum malaria
      • 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_nameArtemether Lumefantrine
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressraps.clinicaltrials@novartis.com
      • applicant_covering_letter1
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      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
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      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantSarah Muthuri
      • declaration_date118-12-2020
      • declaration_principal_investigatorBenhards Ogutu
      • declaration_date218-12-2020
      • placebo_presentNo
      • study_objectives<p>\n Primary objective</p>\n<ul>\n <li>\n <p>\n To assess the key PK parameter of artemether in infants and neonates < 5 kg body weight dosed with the new formulation of artemether-lumefantrine</p>\n <p>\n dispersible tablet</p>\n </li>\n</ul>\n<p>\n Secondary objectives</p>\n<ul>\n <li>\n <p>\n To assess other key PK parameters of artemether, DHA and lumefantrine in infants and neonates <5 kg body weight dosed with the new formulation of artemether-lumefantrine dispersible tablet</p>\n </li>\n <li>\n <p>\n To evaluate the safety and tolerability of the new formulation of artemether-lumefantrine dispersible tablet in infants and neonates <5 kg body weight with acute uncomplicated <em>P. falciparum </em>malaria </p>\n </li>\n <li>\n <p>\n To determine the efficacy of the new formulation of artemether-lumefantrine dispersible tablet for treatment of acute uncomplicated <em>P. falciparum malaria in infants and neonates <5 kg body weight</em></p>\n </li>\n</ul>\n<p>\n Exploratory objectives</p>\n<ul>\n <li>\n <p>\n To assess model-derived exposure metrics based on population PK modeling of artemether, DHA and lumefantrine in infants and neonates <5 kg body weight dosed with the new formulation of artemether-lumefantrine dispersible tablet</p>\n </li>\n <li>\n <p>\n To further evaluate safety of the new formulation of artemether-lumefantrine dispersible tablet in infants and neonates <5 kg body weight</p>\n </li>\n <li>\n <p>\n To explore the effect of the new formulation of artemether-lumefantrine dispersible tablet on gametocytes</p>\n </li>\n</ul>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p style=\"margin-left: 7.2pt;\">\n Subjects meeting any of the following criteria are not eligible for inclusion in this study:</p>\n<ol>\n <li>\n Male or female neonates / infants</li>\n</ol>\n<p style=\"margin-left: 7.2pt;\">\n 2. Body weight <5 kg but ≥ 2kg</p>\n<p style=\"margin-left: 7.2pt;\">\n 3. In Cohort 1, infants aged >28 days; in Cohort 2, neonates aged 1 to ≤ 28 days (3 subgroups: 15-28 days; 8-14 days; 1-7 days)</p>\n<p style=\"margin-left: 7.2pt;\">\n 4. Microscopically confirmed diagnosis of <em>P. falciparum </em>malaria (or mixed infections)</p>\n<ul>\n <li>\n in Cohort 1: of ≥500 and <100,000 parasites/μL asexual <em>P. falciparum parasitemia</em></li>\n <li>\n in Cohort 2: of ≥100 and <100,000 parasites/μL asexual <em>P. falciparum parasitemia</em></li>\n <li>\n either congenital or neonatal</li>\n <li>\n either symptomatic or asymptomatic</li>\n</ul>\n<p style=\"margin-left: 7.2pt;\">\n 5. Parental/legal guardian informed consent obtained and signed prior to any study related procedure. If the parent/legal guardian is unable to read or write, then a witnessed consent according to local ethical standards is permitted (formally documented and witnessed, via an independent trusted witness)</p>\n<p style=\"margin-left: 7.2pt;\">\n 6. The parent/legal guardian is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions for their child and is likely to complete the study as planned</p>\n<p>\n  </p>\n
      • principal_exclusion_criteria<p>\n Subjects meeting any of the following criteria are not eligible for inclusion in this study:</p>\n<ol>\n <li>\n Head circumference < - 2 SD z-score in cm following WHO age and sex-specific reference curves (suspicion of microcephaly)</li>\n</ol>\n<p>\n 2. Severe malnutrition (body mass index (BMI) less than 70% of median normalized WHO reference weight)</p>\n<p>\n 3. Presence of severe malaria (according to WHO 2015 definition)</p>\n<p>\n 4. Hemoglobin < 7 g/dL</p>\n<p>\n 5. HIV status:</p>\n<ul>\n <li>\n in Cohort 1 : patient’s or patient's mother's current treatment with ARV</li>\n <li>\n in Cohort 2 : Mother’s known HIV positive status at patient's birth or mother's current treatment with ARV</li>\n</ul>\n<p>\n 6. Presence of the following signs of a critical condition: apnea-bradycardia, sustained bradycardia, tachycardia, desaturation, hypotension, hypothermia; or other severely deteriorated general condition (based on IMCI criteria in sick infants, WHO 2005)</p>\n<p>\n 7. Presence of any clinically significant neurological condition:</p>\n<ul>\n <li>\n any episode of convulsion during the present illness (in keeping with the IMCI list of general danger signs)</li>\n <li>\n known neurological disorders (e.g. chronic seizure disorders, cerebral palsy)</li>\n</ul>\n<p>\n 8. Presence of clinically significant abnormality of the hepatic and renal systems</p>\n<p>\n 9. History of malabsorption or previous gastrointestinal surgery, or history of radiation therapy that could affect drug absorption or metabolism, or any other disorder or history of a condition that could interfere with drug absorption, distribution, metabolism, or excretion</p>\n<p>\n 10. Patients unable to swallow or whose drinking is impaired</p>\n<p>\n 11. Known hypersensitivity of the patient or either patient's parent to artemether, lumefantrine, any of the excipients of Coartem®/Riamet® Dispersible tablet, or to drugs of similar chemical classes.</p>\n<p>\n 12. Known family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to be associated with prolongation of the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease.</p>\n<p>\n 13. Disturbances of electrolyte balance (e.g. hypokalaemia or hypomagnesaemia)</p>\n<p>\n 14. Presence of any age-adjusted clinically or hematologically relevant laboratory and blood chemistry abnormalities.</p>\n<p>\n 15. Patients who received any antimalarial drug, including antibiotics with antimalarial activity, within 14 days of trial start, or any other prohibited drug.</p>\n<p>\n 16. Patients who received an investigational drug within 5 half-lives of enrollment or participated in an investigational study or within 30 days, whichever is longer.</p>\n<p>\n  </p>\n<p>\n NOTE: Where information is either not available or insufficient (e.g. from medical history, charts) to assess whether a patient meets a specific exclusion criterion, the study site team shall use its best medical judgement to make an inclusion/exclusion decision for the patient.</p>\n<p>\n  </p>\n
      • primary_end_points<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\">\n <tbody>\n <tr>\n <td style=\"width: 338px;\">\n <p>\n <strong>Objective(s)</strong></p>\n </td>\n <td style=\"width: 338px;\">\n <p>\n <strong>Endpoint(s)</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 338px;\">\n <p>\n <strong>Primary objective(s)</strong></p>\n </td>\n <td style=\"width: 338px;\">\n <p>\n <strong>Endpoint(s) for primary objective(s)</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 338px;\">\n <p>\n To assess the key PK parameter of artemether in</p>\n <p>\n infants and neonates < 5 kg body weight dosed with</p>\n <p>\n the new formulation of artemether-lumefantrine</p>\n <p>\n dispersible tablet</p>\n </td>\n <td style=\"width: 338px;\">\n <p>\n Artemether Cmax (represents the</p>\n <p>\n higher concentration between the</p>\n <p>\n concentrations at 1 hour and 2 hours</p>\n <p>\n after first dose)</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 338px;\">\n <p>\n <strong>Secondary objective(s)</strong></p>\n </td>\n <td style=\"width: 338px;\">\n <p>\n <strong>Endpoint(s) for secondary objective(s)</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 338px;\">\n <p>\n To assess other key PK parameters of artemether,</p>\n <p>\n DHA and lumefantrine in infants and neonates <5</p>\n <p>\n kg body weight dosed with the new formulation of</p>\n <p>\n artemether-lumefantrine dispersible tablet</p>\n </td>\n <td style=\"width: 338px;\">\n <p>\n Lumefantrine Day 8 concentration</p>\n <p>\n (C168h) Artemether AUC, DHA and</p>\n <p>\n Lumefantrine Cmax and AUC as</p>\n <p>\n appropriate</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 338px;\">\n <p>\n To evaluate the safety and tolerability of the new</p>\n <p>\n formulation of artemether-lumefantrine dispersible</p>\n <p>\n tablet in infants and neonates <5 kg body weight</p>\n <p>\n with acute uncomplicated <em>P. falciparum </em>malaria</p>\n </td>\n <td style=\"width: 338px;\">\n <p>\n Serious adverse events (SAEs),</p>\n <p>\n adverse events (AEs), and routine</p>\n <p>\n safety laboratory assessments</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 338px;\">\n <p>\n To determine the efficacy of the new formulation of</p>\n <p>\n artemether-lumefantrine dispersible tablet for</p>\n <p>\n treatment of acute uncomplicated <em>P. falciparum</em></p>\n <p>\n malaria in infants and neonates <5 kg body weight</p>\n </td>\n <td style=\"width: 338px;\">\n <p>\n PCR-corrected Adequate Clinical</p>\n <p>\n and parasitological Response</p>\n <p>\n (ACPR) at Days 15, 29, and 43</p>\n <p>\n Uncorrected ACPR at Days 8, 15,</p>\n <p>\n 29, and 43</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 338px;\">\n <p>\n  </p>\n </td>\n <td style=\"width: 338px;\">\n <p>\n Incidence rate of recrudescence and</p>\n <p>\n new infections at Days 15, 29 and 43</p>\n <p>\n Parasite and Fever clearance Times</p>\n <p>\n (PCT and FCT)</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 338px;\">\n <p>\n <strong>Exploratory objective(s)</strong></p>\n </td>\n <td style=\"width: 338px;\">\n <p>\n <strong>Endpoint(s) for exploratory</strong></p>\n <p>\n <strong>objective(s)</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 338px;\">\n <p>\n To assess model-derived exposure metrics based</p>\n <p>\n on population PK modeling of artemether,</p>\n <p>\n DHA and lumefantrine in infants and neonates <5</p>\n <p>\n kg body weight dosed with the new formulation</p>\n <p>\n of artemether-lumefantrine dispersible tablet</p>\n </td>\n <td style=\"width: 338px;\">\n <p>\n Model-derived exposure metrics as</p>\n <p>\n appropriate (e.g. AUC0-24h)</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 338px;\">\n <p>\n To further evaluate safety of the new formulation</p>\n <p>\n of artemether-lumefantrine dispersible tablet in</p>\n <p>\n infants and neonates <5 kg body weight</p>\n </td>\n <td style=\"width: 338px;\">\n <p>\n Neurodevelopment assessment</p>\n <p>\n (Shoklo Malaria Research Unit</p>\n <p>\n Assessment) at Day 4 and at 12</p>\n <p>\n months of age and head</p>\n <p>\n circumference at 12 months of age</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 338px;\">\n <p>\n To explore the effect of the new formulation</p>\n <p>\n of artemether-lumefantrine dispersible tablet on</p>\n <p>\n gametocytes</p>\n </td>\n <td style=\"width: 338px;\">\n <p>\n Number of patients with gametocytes</p>\n <p>\n over time and gametocyte</p>\n <p>\n concentration</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy1
      • 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_exploratory1
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width: 687px;\" width=\"0\">\n <tbody>\n <tr>\n <td style=\"width: 21px; height: 41px;\">\n <p align=\"center\">\n  </p>\n </td>\n <td style=\"width: 87px; height: 41px;\">\n <p align=\"center\">\n <strong>Site staff designation</strong></p>\n </td>\n <td style=\"width: 105px; height: 41px;\">\n <p align=\"center\">\n <strong>Name</strong></p>\n </td>\n <td style=\"width: 48px; height: 41px;\">\n <p align=\"center\">\n <strong>Telephone number</strong></p>\n </td>\n <td style=\"width: 203px; height: 41px;\">\n <p align=\"center\">\n <strong>Cellphone number</strong></p>\n </td>\n <td style=\"width: 219px; height: 41px;\">\n <p align=\"center\">\n <strong>Email address</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 21px; height: 37px;\">\n <p>\n <strong>1</strong></p>\n </td>\n <td style=\"width: 87px; height: 37px;\">\n <p>\n <strong>Principal Investigator</strong></p>\n </td>\n <td style=\"width: 105px; height: 37px;\">\n <p>\n <strong>Professor Berhards Ogutu</strong></p>\n </td>\n <td style=\"width: 48px; height: 37px;\">\n <p>\n <span class=\"baec5a81-e4d6-4674-97f3-e9220f0136c1\" style=\"white-space: nowrap;\">+254-572020798<a href=\"#\" style=\"margin: 0px; border: currentColor; border-image: none; left: 0px; top: 0px; width: 16px; height: 16px; right: 0px; bottom: 0px; overflow: hidden; vertical-align: middle; float: none; display: inline; white-space: nowrap; position: static !important;\" title=\"Call: +254-572020798\"><img src=\"data:image/png;base64,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\" style=\"margin: 0px; border: currentColor; border-image: none; left: 0px; top: 0px; width: 16px; height: 16px; right: 0px; bottom: 0px; overflow: hidden; vertical-align: middle; float: none; display: inline; white-space: nowrap; position: static !important;\" title=\"Call: +254-572020798\" /></a></span></p>\n </td>\n <td style=\"width: 203px; height: 37px;\">\n <p>\n <span class=\"baec5a81-e4d6-4674-97f3-e9220f0136c1\" style=\"white-space: nowrap;\">+254-733-812613<a href=\"#\" style=\"margin: 0px; border: currentColor; border-image: none; left: 0px; top: 0px; width: 16px; height: 16px; right: 0px; bottom: 0px; overflow: hidden; vertical-align: middle; float: none; display: inline; white-space: nowrap; position: static !important;\" title=\"Call: +254-733-812613\"><img src=\"data:image/png;base64,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\" style=\"margin: 0px; border: currentColor; border-image: none; left: 0px; top: 0px; width: 16px; height: 16px; right: 0px; bottom: 0px; overflow: hidden; vertical-align: middle; float: none; display: inline; white-space: nowrap; position: static !important;\" title=\"Call: +254-733-812613\" /></a></span></p>\n </td>\n <td style=\"width: 219px; height: 37px;\">\n <p>\n <u>bernhards.ogutu@usamru-k .org </u></p>\n <p>\n <u>ogutu6@gma il.com</u></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 21px; height: 40px;\">\n <p>\n <strong>2</strong></p>\n </td>\n <td style=\"width: 87px; height: 40px;\">\n <p>\n <strong>Sub-Investigator</strong></p>\n </td>\n <td style=\"width: 105px; height: 40px;\">\n <p>\n Dr Godfrey Allan Otieno</p>\n </td>\n <td style=\"width: 48px; height: 40px;\">\n <p>\n <span class=\"baec5a81-e4d6-4674-97f3-e9220f0136c1\" style=\"white-space: nowrap;\">+254-572020798<a href=\"#\" style=\"margin: 0px; border: currentColor; border-image: none; left: 0px; top: 0px; width: 16px; height: 16px; right: 0px; bottom: 0px; overflow: hidden; vertical-align: middle; float: none; display: inline; white-space: nowrap; position: static !important;\" title=\"Call: +254-572020798\"><img src=\"data:image/png;base64,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\" style=\"margin: 0px; border: currentColor; border-image: none; left: 0px; top: 0px; width: 16px; height: 16px; right: 0px; bottom: 0px; overflow: hidden; vertical-align: middle; float: none; display: inline; white-space: nowrap; position: static !important;\" title=\"Call: +254-572020798\" /></a></span></p>\n </td>\n <td style=\"width: 203px; height: 40px;\">\n <p>\n <span class=\"baec5a81-e4d6-4674-97f3-e9220f0136c1\" style=\"white-space: nowrap;\">+254 733 893481<a href=\"#\" style=\"margin: 0px; border: currentColor; border-image: none; left: 0px; top: 0px; width: 16px; height: 16px; right: 0px; bottom: 0px; overflow: hidden; vertical-align: middle; float: none; display: inline; white-space: nowrap; position: static !important;\" title=\"Call: +254 733 893481\"><img src=\"data:image/png;base64,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\" style=\"margin: 0px; border: currentColor; border-image: none; left: 0px; top: 0px; width: 16px; height: 16px; right: 0px; bottom: 0px; overflow: hidden; vertical-align: middle; float: none; display: inline; white-space: nowrap; position: static !important;\" title=\"Call: +254 733 893481\" /></a></span>, <span class=\"baec5a81-e4d6-4674-97f3-e9220f0136c1\" style=\"white-space: nowrap;\">+254 723 934706<a href=\"#\" style=\"margin: 0px; border: currentColor; border-image: none; left: 0px; top: 0px; width: 16px; height: 16px; right: 0px; bottom: 0px; overflow: hidden; vertical-align: middle; float: none; display: inline; white-space: nowrap; position: static !important;\" title=\"Call: +254 723 934706\"><img src=\"data:image/png;base64,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\" style=\"margin: 0px; border: currentColor; border-image: none; left: 0px; top: 0px; width: 16px; height: 16px; right: 0px; bottom: 0px; overflow: hidden; vertical-align: middle; float: none; display: inline; white-space: nowrap; position: static !important;\" title=\"Call: +254 723 934706\" /></a></span></p>\n </td>\n <td style=\"width: 219px; height: 40px;\">\n <p>\n <a href=\"mailto:Allan.Otieno@usamru-k.org\">Allan.Otieno@usamru-k.org</a></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 21px; height: 20px;\">\n <p>\n <strong>3</strong></p>\n </td>\n <td style=\"width: 87px; height: 20px;\">\n <p>\n <strong>Sub-Investigator</strong></p>\n </td>\n <td style=\"width: 105px; height: 20px;\">\n <p>\n Dr Fredrick Olewe</p>\n </td>\n <td style=\"width: 48px; height: 20px;\">\n <p>\n  </p>\n </td>\n <td style=\"width: 203px; height: 20px;\">\n <p>\n  +254727863357</p>\n </td>\n <td style=\"width: 219px; height: 20px;\">\n <p>\n <a href=\"mailto:fred84doc@gmail.com\">fred84doc@gmail.com</a></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 21px; height: 38px;\">\n <p>\n <strong>4</strong></p>\n </td>\n <td style=\"width: 87px; height: 38px;\">\n <p>\n <strong>Pharmacist</strong></p>\n </td>\n <td style=\"width: 105px; height: 38px;\">\n <p>\n Ruth Ongoro Wasuna</p>\n </td>\n <td style=\"width: 48px; height: 38px;\">\n <p>\n +254  733333530 </p>\n </td>\n <td style=\"width: 203px; height: 38px;\">\n <p>\n <span class=\"baec5a81-e4d6-4674-97f3-e9220f0136c1\" style=\"white-space: nowrap;\">+254 722763832<a href=\"#\" style=\"margin: 0px; border: currentColor; border-image: none; left: 0px; top: 0px; width: 16px; height: 16px; right: 0px; bottom: 0px; overflow: hidden; vertical-align: middle; float: none; display: inline; white-space: nowrap; position: static !important;\" title=\"Call: +254 722763832\"><img src=\"data:image/png;base64,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\" style=\"margin: 0px; border: currentColor; border-image: none; left: 0px; top: 0px; width: 16px; height: 16px; right: 0px; bottom: 0px; overflow: hidden; vertical-align: middle; float: none; display: inline; white-space: nowrap; position: static !important;\" title=\"Call: +254 722763832\" /></a></span></p>\n </td>\n <td style=\"width: 219px; height: 38px;\">\n <p>\n <a href=\"mailto:ruth.wasuna@usamru-k.org\">ruth.wasuna@usamru-k.org</a></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 21px; height: 61px;\">\n <p>\n <strong>5</strong></p>\n </td>\n <td style=\"width: 87px; height: 61px;\">\n <p>\n <strong>Study Coordinator</strong></p>\n </td>\n <td style=\"width: 105px; height: 61px;\">\n <p>\n Ishmael  Osoo Sports</p>\n </td>\n <td style=\"width: 48px; height: 61px;\">\n <p>\n  </p>\n </td>\n <td style=\"width: 203px; height: 61px;\">\n <p>\n +254724106654  / +254733992964.</p>\n </td>\n <td style=\"width: 219px; height: 61px;\">\n <p>\n <u><a href=\"mailto:osoosports@gmail.com%0dishmael.sports@usamru-k.org\">osoosports@gmail.com</a></u></p>\n <p>\n <a href=\"mailto:osoosports@gmail.com%0dishmael.sports@usamru-k.org\">ishmael.sports@usamru-k.org</a></p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The Sponsor has decided that Switzerland (the host country of the Sponsor) will not be conducting this study due to low recruitment potential.</p>\n<p>\n  </p>\n
      • other_details_regulatory_notapproved<p>\n Not applicable. The study is approved in all the other countries participating in the trial</p>\n<p>\n  </p>\n
      • other_details_regulatory_approved<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\">\n <tbody>\n <tr>\n <td style=\"width: 156px;\">\n <p>\n <strong>Country</strong></p>\n </td>\n <td style=\"width: 239px;\">\n <p>\n <strong>Agency</strong></p>\n </td>\n <td style=\"width: 156px;\">\n <p>\n <strong>Date of approval</strong></p>\n </td>\n <td style=\"width: 102px;\">\n <p>\n <strong>Number of sites:</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 156px;\">\n <p align=\"center\">\n Burkina Faso</p>\n </td>\n <td style=\"width: 239px;\">\n <p>\n Ministère de la Santé, de la Population et de la Réforme Hospitalière (MSPR)</p>\n </td>\n <td style=\"width: 156px;\">\n <p>\n 17-Aug-2020</p>\n </td>\n <td style=\"width: 102px;\">\n <p>\n 2</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 156px;\">\n <p align=\"center\">\n Democratic Republic of Congo</p>\n </td>\n <td style=\"width: 239px;\">\n <p>\n Direction de la Pharmacie et du Médicament (DPM)</p>\n <p>\n  </p>\n </td>\n <td style=\"width: 156px;\">\n <p>\n 11-Jun-2020</p>\n </td>\n <td style=\"width: 102px;\">\n <p>\n 1</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 156px;\">\n <p align=\"center\">\n Mali</p>\n </td>\n <td style=\"width: 239px;\">\n <p>\n Ministère de la Santé et des Affaires Sociales (MSAS)</p>\n </td>\n <td style=\"width: 156px;\">\n <p>\n 15-Oct-2020</p>\n </td>\n <td style=\"width: 102px;\">\n <p>\n 1</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 156px;\">\n <p align=\"center\">\n Nigeria</p>\n </td>\n <td style=\"width: 239px;\">\n <p>\n National Agency for Food and Drug Administration and Control</p>\n </td>\n <td style=\"width: 156px;\">\n <p>\n 21-Sep-2020</p>\n </td>\n <td style=\"width: 102px;\">\n <p>\n 1</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n Not applicable to date. Should the study be rejected in any country during the conduct or the review process, the MoH will be informed accordingly.</p>\n<p>\n  </p>\n
      • other_details_regulatory_halted<p>\n Not applicable to date. Should the study be halted in any country during the conduct or the review process, the MoH will be informed accordingly.</p>\n<p>\n  </p>\n
      • estimated_durationApproximately 31 months: First Patient First Visit is planned for 07Jan2020 Last Patient Last Visit is planned for 01Dec2020
      • design_controlled_randomisedNo
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorN/A
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI-Centre for Clinical Research (CCR)
      • single_site_physical_addressKEMRI-Centre for Clinical Research (CCR) Kondele Children\'s Hospital, Off Kisumu-Kakamega Road, P.o. Box, 54-40100, Kisumu. Kenya
      • single_site_contact_personBenhards ogutu
      • single_site_telephone254733966065
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states5
      • number_of_sites
      • multi_country_listBurkina Faso\nDemocratic Republic of Congo\nKenya\nMali\nNIgeria
      • data_monitoring_committeeYes
      • total_enrolment_per_siteApproximately sixteen (16) babies are expected to join this study in Kenya.
      • total_participants_worldwideApproximately ninety-eight (98) babies are expected to join this study worldwide.
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornYes
      • population_newbornYes
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentNo
      • 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_consentYes
      • subjects_specifyInfants and neonates <5 kg body weight. Parental/legal guardian informed consent will be obtained and signed prior to any study related procedure. If the parent/legal guardian is unable to read or write, then a witnessed consent according to local ethical standards is permitted (formally documented and witnessed, via an independent trusted witness)
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBenhards
      • investigator1_middle_nameRagama
      • investigator1_family_nameOgutu
      • investigator1_qualificationMD
      • investigator1_professional_addressKEMRI-Centre for Clinical Research (CCR) Kondele Children\'s Hospital, Off Kisumu-Kakamega Road, P.O. Box, 54-40100, Kisumu Kenya
      • investigator1_telephone+254 572020798
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_No
      • number_participantsApproximately sixteen (16) babies are expected to join this study in Kenya.
      • notification<p>\n None</p>\n
      • approval_date08-03-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted18-12-2020
      • 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<p>\n “The objective of this Phase II/III study was to test the new artemether- lumefantrine dispersible tablet formulation to determine exposure to artemether, DHA and lumefantrine as well as its safety, tolerability and efficacy in patients <5 kg with uncomplicated <em>P. falciparum </em>malaria. The results of artemether and lumefantrine concentration, are in same ranges as in patients ≥5 kg as per historical data from Study B2303, which is also reflected in efficacy and safety outcomes. The PCR-corrected ACPR and overall efficacy was consistent with historical data.</p>\n<p>\n  </p>\n<p>\n The safety profile was consistent with the known safety profile of artemether and lumefantrine. There were no new or unexpected safety signals reported during this study. Neurodevelopmental assessments showed no significant adverse findings in the small sample studied; however, results must be viewed with caution.</p>\n<p>\n  </p>\n<p>\n In conclusion, the results of this study demonstrate the exposures, safety and efficacy of artemether-lumefantrine 2.5 mg:30 mg dispersible tablet formulation at a twice daily dose of 5 mg:60 mg in infants weighing less than 5 kg with acute uncomplicated <em>P. falciparum </em>malaria are similar as previously observed in the pivotal Study B2303, and thus, this dose is found appropriate for the treatment of patients <5 kg</p>\n
      • implication_results<p>\n The results will enable healthcare professionals to take informed decisions based on evidence-based medicine about dosing of artemether lumefantrine in very young patients weighing <5 kg and thereby reducing the chances of inaccurate dosing leading to safety concerns. ”</p>\n<p>\n  </p>\n
      • quantity_imported20
      • quantity_dispensed0
      • quantity_destroyed20
      • quantity_exported0
      • balance_site0
      • final_date0000-00-00
      • modified2025-02-20 09:45:06
      • created2020-12-15 18:53:31
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id610
        • application_id965
        • given_nameBenhards
        • middle_nameRagama
        • family_nameOgutu
        • qualificationMD
        • professional_addressKEMRI-Centre for Clinical Research (CCR) Kondele Children\'s Hospital, Off Kisumu-Kakamega Road, P.O. Box, 54-40100, Kisumu Kenya
        • telephone+254 572020798
        • emailbernhards.ogutu@usamru-k.org
        • created2020-12-15 19:22:49
        • modified2020-12-18 19:46:57
    • SiteDetail(array)
      • 0(array)
        • id844
        • application_id965
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2020-12-15 19:22:49
        • modified2020-12-18 19:46:57
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id474
        • application_id965
        • sponsorNovartis Pharma AG
        • sponsor_typeIndustry
        • contact_personSarah Muthuri
        • addressP O Box 46057 00100 GPO
        • telephone_number254 20 245 9112
        • fax_number
        • cell_number254 722706941
        • email_addresssarah.muthuri@novartis.com
        • created2020-12-15 19:22:49
        • modified2020-12-18 19:46:57
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App Constants

CakePHP Constants

PHP Environment

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• 1/var/www/html/ctr/lib
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• 4-> /var/www/html/ctr/lib/Cake/

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