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    • Application(array)
      • id816
      • user_id81
      • trial_status_id4
      • abstract_of_study<p>\n Malaria is a disease of major public health importance. The only vaccine available is partially effective and targets the pre-erythrocytic stages of the life cycle. Thus, there is a need to identify other potential vaccine targets as well as to develop models to test vaccine efficacy, especially that of transmission-blocking vaccines. Controlled human malaria infection (CHMI) has been shown to be an important tool for the assessment of the efficacy of novel malaria vaccines and drugs. CHMI also allows for the evaluation of immunity to malaria and monitoring of parasite growth rates <em>in vivo</em>. This is particularly useful in individuals from endemic areas with varying levels of exposure and immunity to malaria. Thus, CHMI in individuals with prior exposure to malaria has potential to accelerate malaria vaccine development. In this study, we aim to use CHMI in semi-immune adults to develop a model to assess transmissibility of malaria infection to mosquitoes, to study immune responses that are directed against sexual stages that might block transmission, and as a platform to test vaccines. To achieve this, the study will be carried out in two phases A (N=45 participants) and B (N=60 participants) over a period of 4-6months. We will vary the parasite dose in individuals enrolled for CHMI and use low-doses of anti-malarial drugs to promote the production of gametocytes <em>in vivo</em> (Phase A) and demonstrate transmissibility in mosquito feeding assays (Phase B). Thus, the main outcomes of the study will be: (1) optimisation of sporozoite dose for infections success in individuals with moderate-high malaria exposure; (2) use of sub-curative anti-malaria treatment for induction of gametocytes; and (3) infection of mosquitoes in mosquito feeding assays by induced gametocytes. To achieve this, we will screen up to 250 semi-immune adults who will be recruited from known areas of malaria endemicity in Kenya with varying exposure to malaria and enrol 105 individuals to conduct CHMI studies with serial quantitative polymerase chain reaction (PCR) to measure asexual parasite growth and induction of transmission stages <em>in vivo</em>. In addition, we will comprehensively characterize immunity and identify targets in relation to function assessed by various laboratory assays.</p>\n
      • study_title<p>\n Safety and feasibility of a malaria transmission model in semi-immune Kenyan adults using <em>Plasmodium falciparum</em> sporozoites</p>\n
      • laymans_summary<address>\n <strong>Formal Title: </strong>Safety and feasibility of a malaria transmission model in semi-immune Kenyan adults using <em>Plasmodium falciparum</em> sporozoites</address>\n<address>\n <strong>Lay Title: </strong>Use of malaria infection by injection to study malaria transmission</address>\n<address>\n <strong>What is the problem/background?</strong></address>\n<p>\n Malaria remains a major public health problem with up to half a billion-people infected with the parasite that causes the disease. In recent and ongoing studies, we have conducted controlled malaria infection in 189 Kenyan adults. By measuring malaria parasites in the blood, we have gained insights into the growth of parasites that will guide vaccine development. One other approach to vaccination is to target the transmitting stages of the malaria parasites such that mosquitoes feeding on the infected person would not become infected, thus breaking the life cycle of the parasite. There is a need to develop experimental methods to test the effect of candidate vaccines designed to interrupt transmission to mosquitoes so that vaccines showing evidence of efficacy can then be prioritized for large trials in the field. Furthermore, studying natural immunity in humans to the stages involved in malaria transmission will help characterize potential targets for new vaccines. </p>\n<address>\n <strong>What questions are we trying to answer?</strong></address>\n<p>\n We wish to develop a method to test the efficacy of vaccines and/or drugs designed to block transmission of malaria to mosquitoes and to identify the targets of transmission-blocking immunity to malaria.</p>\n<address>\n <strong>Where is the study taking place, how many people does it involve and how are they selected?</strong></address>\n<p>\n The study will take place in Kilifi, Kenya. The study will involve the recruitment and screening of up to 250 individuals from Ahero and Kilifi to determine eligibility for participation and past exposure to malaria. This will be done after a programme of sensitisation and information giving about the study. The study will be conducted in two phases where individuals with moderate to high malaria exposure will be enrolled to participate in the following:</p>\n<ol>\n <li>\n Phase A (N = 45): “dose-finding” of the dose of sporozoites given and optimisation of the dose of anti-malarial drug that will be used to promote development of transmission stages without clearing the infection completely (i.e. a “sub-curative dose”);</li>\n <li>\n Phase B (N = 60): assessing infectivity of induced malaria transmission stages to mosquitoes.</li>\n</ol>\n<p>\n For each of these phases, selection will be based on level of past malaria exposure and health status. To determine these, blood samples will be taken at the point of screening for each individual participant.</p>\n<address>\n <strong>What does the study involve for those who are in it?</strong></address>\n<p>\n For screening, a blood sample of 21ml will be collected at the time of recruitment. A urine sample and medical history will also be obtained in addition to undergoing a clinical assessment and a test to check the functioning of the heart. For enrollment, a participant will need to have moderate to high malaria exposure and have no clinical disease. Those that meet this criteria, some will be enrolled into phase A and some into phase B (phase A will happen before phase B) for malaria infection studies and be required to stay at an in-patient facility in Kilifi near KEMRI-Kilifi. The participants will be asked to stay at the facility throughout the study so that they are closely monitored by the study staff. To transmit malaria to mosquitoes the human challenge model must first reliably induce infection and of a sufficient duration before being able to develop transmitting stages. We will:</p>\n<ol>\n <li>\n For Phase A: Assign individuals to one of three groups to be given different doses of malaria by injection. These individuals will be further assigned to receive two different anti-malarial drugs (sub-curative treatment)</li>\n <li>\n For Phase B: Based on results from Phase A, give individuals malaria infection by injection at the most successful dose and provide sub-curative treatment that promotes the most transmission stages. At peak time points of transmission stage induction (based on results from Phase A), mosquito feeding assays will be undertaken to determine infectivity to mosquitoes.</li>\n</ol>\n<p>\n Multiple blood samples will be taken for those enrolled for malaria infections (both Phase A and B). For both phases, blood samples will be drawn as follows: a day before infection (40ml); at five days after infection (8ml); twice daily every day from seven days after infection until the day they will receive a sub-curative treatment (cumulative total of 185ml); and then once daily afterwards to twenty-one days after infection (cumulative total of 70ml); then every other day from day twenty-one until day forty-two (cumulative total of 71ml); once daily during curative treatment (cumulative total of 18ml);  and on day fifty-six after infection (40ml). In addition, for participants enrolled into Phase B, direct skin mosquito feeding and blood samples for mosquito membrane feeding assays will also be taken to assess mosquito infectivity (cumulative total of 28ml). The specific days for assessing mosquito infectivity will be dependent on the results from Phase A of the study. For the entire duration of the study (4-6months), a total of 465ml per participant of blood will be drawn for those enrolled in Phase A and a total of 493mls for those in Phase B. This total volume of blood is less than the volume taken during a blood donation. In addition to blood sampling, clinical assessments will be repeated a day before infection including collection of a urine sample and measurements of weights and heights. Observed sub-curative treatment for malaria will be administered on the day the parasites reach a set threshold and a curative dose on day forty-two after infection.</p>\n<address>\n <strong>What are the benefits and risks/costs of the study for those involved?</strong></address>\n<p>\n Controlled human malaria infection has been conducted in one hundred and eighty-nine (189) healthy adults in Kenya (Hodgson et al Front Microbiol. 2014 (Nairobi, N=28 volunteers, 2013) and KEMRI/SERU/CGMR-C/029/3190 (Kilifi, N=161 volunteers, 2016-2018)) and has been proven safe in these individuals. The risks relate to the possibility of developing an allergic reaction upon administration of the malaria infection. In addition, participants may develop signs and symptoms of malaria after infection which are unpleasant, may result in development of severe malaria due to the higher doses of sporozoites being given and may develop some side effects to the drugs used for treatment (sub-curative and curative doses). There are no direct benefits to individuals participating in this study other than information about their health. However, all participants will have their transport costs reimbursed and compensated for all out of pocket expenses for the entire duration of the study.</p>\n<address>\n <strong>How will the study benefit society?</strong></address>\n<p>\n This work is necessary for enhancing our understanding of how malaria transmission stages develop, the immune targets involved and ability to test interventions such as vaccines in populations that have past exposure to malaria. The successful application of such interventions will benefit society by reducing malaria transmission, a major cause of illness, death and impediment to national development. An adaptation of the controlled human malaria infection provides a way of studying transmission of malaria in a very detailed way that is not possible using natural infections, and we believe that this step is now necessary to inform vaccine design and efficacy.</p>\n<address>\n <strong>When does the study start and finish?</strong></address>\n<p>\n The study will start upon receipt of ethical clearance. Data collection, analysis and write up will take place over three years.</p>\n
      • short_titleUse of malaria infection by injection to study malaria transmission
      • protocol_noECCT/19/08/01
      • version_noVersion 3.0
      • date_of_protocol27-03-2019
      • study_drugPfSPZ Challenge CHMI-Transmod
      • disease_conditionMalaria
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressregulatory@kemri-wellcome.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_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data0
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantMelissa Kapulu
      • declaration_date105-08-2019
      • declaration_principal_investigatorMelissa Kapulu
      • declaration_date205-08-2019
      • placebo_presentNo
      • study_objectives<address>\n <strong>Primary objective</strong></address>\n<p>\n To adapt the Controlled Human Malaria Infection (CHMI) model using <em>P. falciparum</em> sporozoites to induce gametocytes and assess their infectivity to mosquitoes.</p>\n<p>\n <strong>Secondary objective(s)</strong></p>\n<address>\n 1. To determine the safety of varied increased doses of <em>P. falciparum</em> sporozoites in CHMI delivered by Direct Venous Inoculation (DVI) in semi-immune volunteers and optimise the dose of sporozoites that results in 100% infectivity in moderate to highly exposed adults;</address>\n<address>\n 2. To determine if the prevalence, peak density and peak time point of gametocytes is altered by drug-regimen and determine the area under the curve of density over time;</address>\n<address>\n 3. To determine the infectivity of drug-induced gametocytes in mosquito feeding assays;</address>\n<address>\n 4. To measure immunity to gametocyte antigens and determine associations between immunity and transmission-blocking activity in the CHMI model;</address>\n<address>\n 5. To explore the perceptions, attitudes, and experiences of research participants and other community and professional stakeholders involved in the CHMI study.</address>\n
      • principal_inclusion_criteria<ul>\n <li>\n Healthy adults aged 18 to 45 years.</li>\n <li>\n Able and willing (in the Investigator’s opinion) to comply with all study requirements.</li>\n <li>\n Informed consent.</li>\n <li>\n Use of effective method of contraception for duration of study (women only). We will ask the female volunteers to come with their family planning records to verify. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female subject’s entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository).</li>\n</ul>\n
      • principal_exclusion_criteria<p>\n Any of the following constitutes exclusion criterion:</p>\n<ul>\n <li>\n Body weight of less than 50kg or body mass index (BMI) less than 18 or greater than 25 kg/m² at screening.</li>\n <li>\n Use of systemic antibiotics with known antimalarial activity within 30 days of administration of PfSPZ Challenge (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin).</li>\n <li>\n Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.</li>\n <li>\n Current participation in another clinical trial or recent participation within 12 weeks of enrolment.</li>\n <li>\n Prior receipt of an investigational malaria vaccine.</li>\n <li>\n Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed). This will also include Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) positivity.</li>\n <li>\n Use of immunoglobulins or blood products within 3 months prior to enrolment.</li>\n <li>\n Any serious medical condition reported or identified during screening that increases the risk of CHMI.</li>\n <li>\n Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination.</li>\n <li>\n Women only; pregnancy, or an intention to become pregnant during the duration of the study.  </li>\n <li>\n Sickle cell trait or disease.</li>\n <li>\n History of drug or alcohol abuse.</li>\n <li>\n Known hypersensitivity to or contraindications for use of artemether-lumefantrine, chloroquine, piperaquine, primaquine, sulfadoxine-pyrimethamine, or history of severe (allergic) reactions to mosquito bites.</li>\n <li>\n Confirmed gametocyte positivity at screening and/or a day before challenge</li>\n <li>\n Confirmed parasite positive by PCR a day before challenge i.e. at C-1.</li>\n</ul>\n<p>\n <strong><em>Exclusion Criterion on Day of Challenge </em></strong></p>\n<ul>\n <li>\n Acute disease, defined as moderate or severe illness with or without fever (temperature >37.5^oC).</li>\n</ul>\n
      • primary_end_points<p>\n Not applicable. There are no primary endpoints.</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_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyHuman challenge study with deliberate infection of participants to induce transmission stages and understand immunogenicity.
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n Medical officer - 1<br />\n Clinical officer - 2<br />\n Nurses - 2<br />\n Fieldworkers - 5<br />\n Research and Assistant Research Officers - 2<br />\n Study Coordinator - 1<br />\n Pharmacisit - 1<br />\n Data Manager - 1<br />\n Data Clerk - 2<br />\n The inpatient facility is already staffed with 3 clincians, 1 paediatrician and 20 nurses.<br />\n All staff are trained in basic life support and resuscitation facilitaties are available.</p>\n
      • other_details_explanation<p>\n Not applicable.</p>\n
      • other_details_regulatory_notapproved<p>\n Submission is only to PPB.</p>\n
      • other_details_regulatory_approved<p>\n Not applicable.</p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable.</p>\n
      • estimated_duration3 years
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI-Wellcome Trust Research Programme (KWTRP) Centre for Geographic Medical Research - Coast (CGMRC), Kilifi, Kenya.
      • single_site_physical_addressKEMRI-Wellcome Trust Research Programme, Off Bofa Road, Kilifi County Hospital, Kilifi, Kenya
      • single_site_contact_personMelissa Kapulu
      • single_site_telephone+254717501319
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site105
      • total_participants_worldwide105
      • 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_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_nameMelissa
      • investigator1_middle_name
      • investigator1_family_nameKapulu
      • investigator1_qualificationPhD
      • investigator1_professional_addressKEMRI-Wellcome Trust Research Programme, P. O. Box 230, Kilifi, Kenya 80108
      • investigator1_telephone+254709983463
      • investigator1_emailmkapulu@kemri-wellcome.org
      • organisations_transferred_No
      • number_participants105
      • notification
      • approval_date15-11-2019
      • submitted1
      • deleted0
      • deleted_date2019-08-09 08:51:39
      • deactivated0
      • date_submitted27-02-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
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      • modified2024-07-29 09:25:54
      • created2019-07-18 14:56:05
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        • id506
        • application_id816
        • given_nameMelissa
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        • family_nameKapulu
        • qualificationPhd
        • professional_addressKEMRI-Wellcome Trust Research Programme, P. O. Box 230, Kilifi, Kenya 80108
        • telephone+254709983463
        • emailmkapulu@kemri-wellcome.org
        • created2019-07-18 15:09:17
        • modified2020-02-27 12:45:15
      • 1(array)
        • id507
        • application_id816
        • given_namePhilip
        • middle_name
        • family_nameBejon
        • qualificationBSc MBBS PhD
        • professional_addressKEMRI-Wellcome Trust Research Programme, P. O. Box 230, Kilifi, Kenya 80108
        • telephone+254709983549
        • emailpbejon@kemri-wellcome.org
        • created2019-07-18 15:10:33
        • modified2020-02-27 12:45:15
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        • created2019-07-18 15:09:17
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        • id395
        • application_id816
        • sponsorUniversity of Oxford
        • sponsor_typeResearch Institution
        • contact_person
        • addressUniversity Offices, Wellington Square, Oxford, OX1 2JD, UK
        • telephone_number+44 1865 270000
        • fax_number
        • cell_number+44 1865 270000
        • email_addressresearch.services@admin.ox.ac.uk
        • created2019-07-18 15:09:17
        • modified2020-02-27 12:45:15
  • 1(array)
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      • id773
      • user_id81
      • trial_status_id8
      • abstract_of_study<p>\n <strong>ABSTRACT</strong></p>\n<p>\n Shigella species are one of the leading causes of diarrhoea in our region affecting primarily infants and children and diarrhoeal disease accounts for close to half a million under five deaths per year worldwide. Following an acute infection shigellosis is associated with post infective complications, developmental repercussions, cognitive impairment and a negative impact on growth. We propose to evaluate the safety and reactogenicity of a candidate Shigella vaccine. Shigella4V, is composed of O-antigen polysaccharides (PS) from four different <em>Shigella</em> strains representing the most epidemiologically relevant strains: <em>S. sonnei</em>, <em>S. flexneri</em> 2a, 3a and 6, conjugated to the exoprotein A of P. aeruginosa EPA. This will be a first-in human trial.  However, several biconjugate vaccines, and one component of Shigella4V have already been evaluated and have been found to be safe and immunogenic. We will conduct a double blind, multi-site trial in KEMRI-CGMRC and KEMRI/MRD-K, Kericho in 2 steps. Step 1 will involve a safety cohort at KEMRI-CGMRC-.  We will use a randomised control, age descending, dose-escalating approach to evaluate safety and reactogenicity in 16 adults (18-50 years), 48 young children (aged 2-5 years) and 60 infants aged 8-10 months of age. The second step will aim to enrol 468 infants to further evaluate safety and identify the optimum immunogenic dose. Infants in step 2 will be randomised on enrolment to 1 of 4 vaccine doses of (4 ,12, 24, 48 µg) or control vaccines. Adults will receive a 2 dose schedule, 1 month apart  with a total of 7 visits in clinic, and they will be in the trial for about 8 months; children will receive a 3 dose schedule (2 doses 1 month apart then a booster dose 6 months after the 2nd dose) with a total of  10 visits in clinic and they will be in the trial for about 13 months;  infants will receive a 3 dose schedule (2 doses  three months apart then a booster dose 6 months after the 2^nd dose) and a total of 11 visits in clinic, and they  will be in the trial for approximately 15 months. For each vaccine dose, formulation with and without Aluminium adjuvant will be tested.</p>\n
      • study_title<p>\n Safety and immunogenicity of a Shigella-tetravalent bioconjugate vaccine: A phase 1/2 randomized controlled and age descending study including dose finding in 9-month-old infants</p>\n
      • laymans_summary<div>\n  </div>\n<div>\n <strong>What is the problem/background?</strong></div>\n<div>\n LimmaTech Biologics Ab (LMTB) develops vaccines called “glycoprotein bioconjugates”</div>\n<div>\n through a new process. Bioconjugates are sugar/protein mixtures that are made using bacterial</div>\n<div>\n cells. Although this is a first in human trial of this precise bioconjugate, six previous clinical</div>\n<div>\n studies have been conducted with the same technology and protein component as used for this</div>\n<div>\n vaccine. Vaccination with bioconjugates in more than 1000 healthy adults has been reported</div>\n<div>\n as safe and well tolerated. This trial will evaluate a vaccine against Shigella, a disease that</div>\n<div>\n causes diarrhoeal illness. The vaccine targets a disease of major importance for</div>\n<div>\n children/infants in low and middle-income countries (LMICs). According to the Global</div>\n<div>\n Burden of Disease study 2015, diarrhoea is the fourth leading cause of death for children and</div>\n<div>\n is responsible for 8.6% of all deaths of children aged under 5years. The impact of diarrheal</div>\n<div>\n disease (DD) goes well beyond mortality, causing a significant amount of disease that mostly</div>\n<div>\n affects children under 5 years of age. Shigella is the leading pathogen causing DD in LMICs</div>\n<div>\n in children > 1 year of age and is among the top six causes of diarrhoea in children < 1 year.</div>\n<div>\n <strong>What questions are we trying to answer?</strong></div>\n<div>\n We plan to evaluate if Shigella4V, a candidate shigella vaccine, is safe at different doses in</div>\n<div>\n healthy Kenyan adults (aged 18-50 years), young children (aged 2-5 years) and infants (8-10</div>\n<div>\n months) and investigate the immune response following vaccination. We will also determine</div>\n<div>\n the ideal dose for an adequate immune response and the associated safety profile in infants.</div>\n<div>\n <div>\n <strong>Where is the study taking place, how many people does it involve and how are they</strong></div>\n <div>\n <strong>selected?</strong></div>\n <div>\n The study is taking place in two research sites; CGMR-C (Kilifi site) and in CCR (Kericho</div>\n <div>\n site). We aim to recruit healthy participants, exclusion will include conditions such as HIV,</div>\n <div>\n hepatitis B and C, heart, lung and conditions, pregnancy amongst others. This study will</div>\n <div>\n evaluate the safety and immune responses to the vaccine in 2 steps. The 1st step will recruit 16</div>\n <div>\n adults, 48 young children and 60 infants at one research site. Once safety has been</div>\n <div>\n established in this first step, we will progress to determine the best dose in 468 infants at both</div>\n <div>\n sites until the target number is enrolled. We will screen potential participants until we identify</div>\n <div>\n the required number of healthy participants from the different age groups.</div>\n <div>\n <strong>What does the study involve for those who are in it?</strong></div>\n <div>\n Individuals who provide consent and pass screening examination will be enrolled in the study.</div>\n <div>\n Screening will involve a series of blood tests to check for good health, an examination and a</div>\n <div>\n urine test for pregnancy in women. All participants will have pre-test counselling for</div>\n <div>\n Hepatitis and HIV as per local practices and guidelines. Additionally, participants at the</div>\n <div>\n KEMRI/CGMRC site will be screened for sickle cell disease (SCD) after pre-test counselling.</div>\n <div>\n Such test will not be routinely done at the site in Kericho as not supported by the geographical</div>\n <div>\n incidence of SCD. For individuals who are selected for participation, blood will be drawn at</div>\n <div>\n the different time-points (infant volumes will be described in SSA and will be within the</div>\n <div>\n limits stipulated by the World Health Organisation/National Institute of Health Guidelines).</div>\n <div>\n Adults will have an average 459mls taken over 8-10 months, Children 120mls over 13-16</div>\n <div>\n months and infants 90mls over 15-18 months in Kilifi and 130 mls in Kericho. Adults will</div>\n <div>\n have 75 mls of blood taken at each visit except screening when 9 mls will be taken. Children</div>\n <div>\n will have 12 mls taken at all visits. Infants in Kilifi will have 5mls taken at 6 visits and 12 mls</div>\n <div>\n at 5 visits. Infants in Kericho will have on average 12mls taken at 11 visits. The higher blood</div>\n <div>\n volumes collected in a subpopulation of infants (Kericho site) will allow exploratory analyses</div>\n <div>\n for further evaluation of the immune response to the Shigella vaccine. Repeat blood samples</div>\n <div>\n may be taken to verify abnormal results. Urine samples will be collected for adult females to</div>\n <div>\n test for pregnancy and medical history will also be obtained in addition to undergoing a</div>\n <div>\n clinical assessment. Listening to the heart will serve as an assessment of heart function with further investigations if clinically indicated. Those that pass screening will be enrolled in the</div>\n <div>\n trial and for those that don’t if a clinically significant condition is identified they will be</div>\n <div>\n counselled as appropriate then referred to a government facility. Eligible participants will be</div>\n <div>\n randomised to receive Shigella 4V or a control vaccine. Blood will be taken at screening,</div>\n <div>\n prior to each vaccination (to check baseline immunity to Shigella4V in all participants and for</div>\n <div>\n rabies in a small group of the children receiving rabies as a control vaccine), and at several</div>\n <div>\n time points (2 to 3 time points) post each vaccination (to evaluate response to vaccination).</div>\n <div>\n There will be a total of 7 clinic visits for adults, 10 for children and 11 for infants, plus home</div>\n <div>\n visits whenever needed in the week following each vaccination. Should a participant develop</div>\n <div>\n diarrhoea during the course of the study 4mls of blood will be collected in children and</div>\n <div>\n infants and 9 mls of blood will be collected in adults and a stool sample to determine if</div>\n <div>\n diarrhea was caused by Shigella and treatment will be provided. The study duration for each</div>\n <div>\n participant will be approximately 8 to 10 months for adults, 13 to 16 months for children and</div>\n <div>\n 15 to 18 months for infants.</div>\n <div>\n <strong>What are the benefits and risks/costs of the study for those involved?</strong></div>\n <div>\n Participants may benefit from receipt of the vaccine if the immune response is favourable and</div>\n <div>\n the vaccine is safe. Participants will also have close oversight and treatment support from the</div>\n <div>\n study team although this will primarily be for risk monitoring. Participants will benefit from a</div>\n <div>\n vaccine against meningitis (adults and infants), rabies (children) or an additional dose of</div>\n <div>\n DTaP vaccine that will be administered to the infants of the control group and offered free of</div>\n <div>\n charge at the end of the study, to the infants randomized to Shigella4V. Although the</div>\n <div>\n administration schedule of the rabies vaccine being used has been evaluated in clinical trials it</div>\n <div>\n is currently not standard practice, therefore for all children we will recommend that should</div>\n <div>\n they have exposure to high risk bite they get full post-exposure prophylaxis.</div>\n <div>\n There will also be wider benefit in the field of shigella vaccine development and in building</div>\n <div>\n on data available on safety and immune responses to bioconjugate vaccines. Although 1 of the</div>\n <div>\n 4 components of the vaccine has been evaluated in humans before this will be the first study</div>\n <div>\n of Shigella 4V in humans, however 6 very similar vaccines have been evaluated in >1000</div>\n <div>\n healthy adults and been found to be safe and illicit a good immune response. A careful</div>\n <div>\n approach to vaccinate a small number of adults sequentially then children and infants with increasing doses and with close follow up in the days and months following vaccination have</div>\n <div>\n been planned to safeguard the safety of all participants.</div>\n <div>\n At its first administration, Shigella4V will be co-administered with the measles-rubella</div>\n <div>\n vaccine in infants which is routinely given at 9 months of age. Several trials have shown an</div>\n <div>\n acceptable safety profile and non-inferiority in the immune-response when conjugate vaccines</div>\n <div>\n are co-administrated together with measles and rubella vaccine. Furthermore immune</div>\n <div>\n response to measles and rubella will be analysed. Higher volumes of blood are being collected</div>\n <div>\n from infants at KEMRI/MRD-K, Kericho to allow for detailed analysis of the immune</div>\n <div>\n response to all components of the Shigella 4V vaccine. Recurrent venepuncture can lead to</div>\n <div>\n anaemia and as such we will monitor heamoglobin levels to ensure we only collect the</div>\n <div>\n volumes of blood planned at the KEMRI/MRD-K, Kericho site if the haemoglobin (Hb) is</div>\n <div>\n 10g/dL or above. Hemoglobin monitoring will be done at the clinic using HemoCue method</div>\n <div>\n prior to the visit blood draw. Should the level fall below 10g/dL blood volumes will be taken</div>\n <div>\n as specified at KEMRI-CGMRC.</div>\n <div>\n Participants will not have any costs associated to their participation to this trial.</div>\n <div>\n <strong>How will the study benefit society?</strong></div>\n <div>\n Diarrhoea is a big problem all around the world and there is a need to develop vaccines for</div>\n <div>\n vulnerable populations-such as infants and young children, particularly in endemic areas. This</div>\n <div>\n study will build on safety and immunogenicity data of Shigella4V and will provide safety and</div>\n <div>\n immune responses which will inform the nature and need of clinical development of this</div>\n <div>\n vaccine. There is reason to believe this is a promising candidate vaccine given components of</div>\n <div>\n the vaccine and vaccines made using a similar technology have been shown to be safe and to</div>\n <div>\n raise an immune response.</div>\n <div>\n <strong>When does the study start and finish?</strong></div>\n <div>\n The study will start on receipt of ethical and regulatory approvals and will take approximately</div>\n <div>\n 2.5 years.</div>\n</div>\n<p>\n  </p>\n
      • short_titleA study to determine if a new shigella vaccine (Shigella4V) is safe, induces immunity and the best dose among Kenyan infants.
      • protocol_noECCT/19/04/01
      • version_no3.1
      • date_of_protocol09-07-2019
      • study_drugShigella-tetravalent bioconjugate vaccine
      • disease_conditionShigellosis
      • 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_nameMenveo, Verorab, Infanrix
      • comparator_registeredYes
      • comparator_countriesMenveo: Not registered in Kenya\nVerorab: Registered in Kenya\nInfanrix: Registered in Kenya
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressctfuser@kemri-wellcome.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_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data0
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr. Mainga Hamaluba, Dr. Josphat Kosgei
      • declaration_date103-04-2019
      • declaration_principal_investigatorDr. Mainga Hamaluba
      • declaration_date203-04-2019
      • placebo_presentYes
      • study_objectives<div>\n Study objectives</div>\n<div>\n - The primary objective of this Phase 1/2 study is to obtain first-in-human data (safety</div>\n<div>\n and immunogenicity) following administration of 9-month-old infants and to identify</div>\n<div>\n the preferred dose of Shigella4V.</div>\n<div>\n Secondary objectives:</div>\n<div>\n - To further evaluate safety of Shigella4V through collection of laboratory values from</div>\n<div>\n safety laboratory tests.</div>\n<div>\n - To evaluate immunogenicity of Shigella4V when administered to adults and in 2-5-</div>\n<div>\n year-old children.</div>\n<div>\n - To evaluate persistence of the vaccine-induced immune response, 6 months after the</div>\n<div>\n primary vaccination schedule.</div>\n<div>\n - To evaluate the immunological response and immune persistence induced by a booster</div>\n<div>\n dose of Shigella4V in children and infants.</div>\n<div>\n <div>\n Exploratory objectives:</div>\n <div>\n In this study, additional investigations may include, but are not limited to, the following</div>\n <div>\n immunological and efficacy objectives:</div>\n <div>\n - IgA immunological response induced by vaccination with Shigella4V (i.e. Serum IgA</div>\n <div>\n responses and fold-increases between post- and pre-vaccination samples, from</div>\n <div>\n participants of step 1 and 2).</div>\n <div>\n - Functionality of the antibodies generated following vaccination with Shigella4V (i.e</div>\n <div>\n measuring serum bactericidal activity (SBA) post and pre-vaccination from</div>\n <div>\n participants of step 1 and 2).</div>\n <div>\n - Development of B-memory response in the vaccinated participants, against serotypes</div>\n <div>\n included in Shigella4V.</div>\n <div>\n - Impact of vaccination toward incidence of diarrhoea episodes caused by Shigella</div>\n <div>\n strains of vaccine serotypes (i.e. Number of participants with Shigella positive</div>\n <div>\n (culture or PCR confirmed) diarrhoea in vaccinated vs. control group).</div>\n <div>\n - Impact of vaccination on the severity of symptoms associated with Shigella-positive</div>\n <div>\n diarrhoea in vaccinated vs. control groups.</div>\n <div>\n - To evaluate concomitant administration of measles-rubella vaccine in 9-month-oldinfants.</div>\n <div>\n The study team will administer the measles-rubella vaccine to allow for its</div>\n <div>\n co-administration with the Shigella vaccine. The team will work with the county</div>\n <div>\n officials to make arrangements for the study participants to receive the measlesrubella</div>\n <div>\n vaccine in the study sites</div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n All participants shall satisfy the following criteria:</p>\n<p>\n <strong>All ages </strong></p>\n<ol>\n <li>\n Healthy by medical history, laboratory findings and physical examination before entering into the study (Participants with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator)</li>\n <li>\n Seronegative for HIV, hepatitis B and C (as per screening laboratory tests)</li>\n <li>\n Resident in the study area village during the whole trial period (Kilifi -Kilifi Health and Demographic Surveillance System (Described in more detail in the SSA); Kericho-a 75km radius from the Kericho Clinical Research Centre).</li>\n <li>\n Previously completed routine primary vaccinations (6,10 and 14 weeks or thereabouts) to the best knowledge of the participant/parent/guardian.</li>\n <li>\n Signed/thumb written informed consent, in accordance with local practice, provided by adult volunteers (participants 18 years of age and older), parents or legal representatives for children and infants participants as applicable, who, in the opinion of the investigator, can and will comply with the requirements of the protocol</li>\n <li>\n Demonstrated comprehension of the protocol procedures by passing score of 90% or better on a written/verbal comprehension test.</li>\n</ol>\n<p>\n <strong>Adults</strong></p>\n<ol>\n <li value=\"7\">\n Female and male participants between, and including 18-50 years at the time of first vaccination</li>\n <li>\n Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. Female volunteers of childbearing potential may be enrolled in the study if the participant: has a negative urine pregnancy test at the day of screening and vaccinations, respectively, and</li>\n</ol>\n<ul>\n <li>\n agree to use effective contraception for 30 days prior to vaccination and</li>\n <li>\n agree to continue contraception at least for 2 months after completion of vaccination series.</li>\n</ul>\n<p>\n <em>To demonstrate adequate contraception use we will ask female participants to attend with their family planning records for verification. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female participant’s entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository)</em></p>\n<p>\n  </p>\n<p>\n <strong>Children and Infants</strong></p>\n<ol>\n <li value=\"7\">\n Female and male aged 9 months (+/- 1 month) old (infants) or between, and including, 2-5 years of age (children) at the time of the first vaccination</li>\n <li>\n Born full-term (i.e. after a gestation period of 37 to less than 42 completed weeks)</li>\n</ol>\n
      • principal_exclusion_criteria<p>\n A participant meeting any of the exclusion criteria listed below must be excluded from participating in the trial.</p>\n<p>\n <strong>All ages</strong></p>\n<ol>\n <li>\n Any clinically significant deviation from the normal range in biochemistry or haematological blood tests. Normal ranges for Hb are site specific, as following:</li>\n</ol>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:150px;\">\n <p>\n Hb values (g/dl)</p>\n </td>\n <td style=\"width:85px;\">\n <p>\n Kilifi</p>\n </td>\n <td style=\"width:85px;\">\n <p>\n Kericho</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:150px;\">\n <p>\n Infants and Children</p>\n </td>\n <td style=\"width:85px;\">\n <p>\n 8.2-12.7</p>\n </td>\n <td style=\"width:85px;\">\n <p>\n 10-15.6</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:150px;\">\n <p>\n Adults_Women</p>\n </td>\n <td style=\"width:85px;\">\n <p>\n 8.0-14.9</p>\n </td>\n <td style=\"width:85px;\">\n <p>\n 9.5-16.1</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:150px;\">\n <p>\n Adults_Men</p>\n </td>\n <td style=\"width:85px;\">\n <p>\n 10.6-17.0</p>\n </td>\n <td style=\"width:85px;\">\n <p>\n 13.3-18.1</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p style=\"margin-left:36.0pt;\">\n  </p>\n<ol>\n <li value=\"2\">\n Suspected or known hypersensitivity (including allergy) to any of the vaccine components or to previous vaccine, or to medicinal products or medical equipment whose use is foreseen in this study</li>\n <li>\n Clinical conditions representing a contraindication to intramuscular vaccination and blood draws         </li>\n <li>\n Any confirmed or suspected immunosuppressive or immune-deficient condition.</li>\n <li>\n Systemic administration of corticosteroids (PO/IV/IM): prednisone ≥20 mg/day, or equivalent for more than 14 consecutive days from birth (for infants) / within 90 days prior to informed consent. Inhaled except for doses > 800 mg/day and topical steroids are allowed.</li>\n <li>\n Administration of antineoplastic or radiotherapy from birth / within 90 days prior to informed consent. Participants may be on chronic or as needed medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to participant safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition</li>\n <li>\n Known exposure to <em>Shigella</em> during lifetime of the subject</li>\n <li>\n Concurrently participating in another clinical study, or participation in the preceding month, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device)</li>\n <li>\n Acute disease and /or fever at the time of enrolment</li>\n</ol>\n<p>\n Note: enrolment may be postponed/delayed until such transient circumstances have terminated</p>\n<ol>\n <li value=\"10\">\n History of any malignancy of lymphoproliferative disorder</li>\n <li>\n Known to be part of study personnel or being a close family member to the personnel conducting this study.</li>\n <li>\n Previous history of significant persistent neutropenia, or drug related Neutropenia</li>\n <li>\n Adults with clinical wasting; children with weight-for-age Z score less than -3SD.</li>\n <li>\n History of any chronic or progressive disease (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease) that according to judgment of the investigator could interfere with the study outcomes or pose a threat to the participant's health</li>\n <li>\n History of surgical splenectomy or Sickle cell disease (SCD test performed  at KEMRI-CGMRC only).</li>\n <li>\n Administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine</li>\n <li>\n Any medical, social condition, or occupational reason that, in the judgment of the investigator, is a contraindication to protocol participation or impairs the volunteer's/parent’s/guardian’s ability to give informed consent, increases the risk to the potential participant because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data   .</li>\n <li>\n Women who are breastfeeding</li>\n</ol>\n<p>\n <strong>Adults</strong></p>\n<ol>\n <li value=\"19\">\n History of chronic alcohol consumption and/or drug abuse. Chronic alcohol consumption is defined as: a prolonged period of frequent, heavy alcohol use; the inability to control drinking once it has begun; physical dependence manifested by withdrawal symptoms when the individual stops using alcohol; tolerance, or the need to use more and more alcohol to achieve the same effects; a variety of social and/or legal problems arising from alcohol use.</li>\n</ol>\n
      • primary_end_points<p>\n <strong><u>Safety</u></strong></p>\n<p>\n Safety and tolerability of the candidate vaccine Shigella4V as determined by occurrence, severity and relationship, of solicited and unsolicited adverse events (AEs) and serious AEs (SAEs), through:</p>\n<ul>\n <li>\n solicited local and systemic AEs during 7 days following each vaccination </li>\n <li>\n unsolicited AEs during 28 days following each vaccination</li>\n <li>\n SAEs and medically relevant AEs throughout the study duration</li>\n</ul>\n<p>\n <strong><u>Immunology</u></strong><strong>:</strong></p>\n<ul>\n <li>\n Serum IgG responses and fold-increases between post- and pre-vaccination samples from infants of step 2, as determined by ELISA against LPS corresponding to the 4 Shigella serotypes included in the Shigella4V bioconjugate.</li>\n</ul>\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 and dose finding
      • trial_human_pharmacology0
      • trial_administration_humans1
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Kilifi: </strong></p>\n<p>\n The KEMRI-Wellcome Trust Research Programme has long history of conducting clinical trials in illnesses that cause high disease burden and mortality in the local community. These range from locally led ‘academic’ type clinical research and product development/drug registration trials.</p>\n<p>\n The programme has built up experience from assessing safety and efficacy in phase I trials through to evaluating real-life effectiveness in phase IV trials.</p>\n<p>\n There are ongoing trials in the wards and out-patient departments of Kilifi District Hospital, health centres and dispensaries within Kilifi district.</p>\n<p>\n The Clinical Trials Facility (CTF) of the KEMRI-Wellcome Trust Research Programme was set up in 2006 to provide a global standard trial centre within the collaborative programme. Based in Kilifi, the CTF works to help ensure all trials conducted meet international quality standards from the point of setting the research question to analysis and reporting. The core aim of the CTF is to enhance the way trials are organized while at the same time providing an optimum environment for developing highly skilled African trialists. The Clinical Trial Laboratory (CTL) is Good Clinical Laboratory Practices (GCLP) accredited has been audited by regulatory bodies and certification institutions like GlasxoSmithKline Biological (GSK Biologicals), Contract Lab Services (CLS) and Food and Drug Administration (FDA).</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n In addition to the principal investigator and co-investigators, we will have the following staff: Medical officer-1, Clinical officer - 3, Nurses -2, Fieldworkers - 12, Assistant Research Officer - 2, Study Coordinator -1, Pharmacisit-1</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Pharmacy Technician-1, Data Manager-1, Data Clerk-2, and Lab Archivist-1</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The inpatient facility is already staffed with 3 clincians, 1 paediatrician and 20 nurses. All staff are trained in basic life support and resuscitation facilitaties are available</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Kericho:</p>\n<p>\n The KEMRI/WRP CRC is the primary research site in USAMRD-K. Situated on the grounds of the Kericho County Referral Hospital (KDH)/Ministry of Health (MoH), the 7100 square feet CRC supports both research and HIV care & treatment in the southern Rift Valley Province. The CRC is staffed with 5 doctors, 2 pharmacists, 8 clinical officers, 10 nurses, 38 laboratory and auxiliary staff. The Principal Investigator at the site for this study is Dr Josphat Kosgei and the Study Coordinator is Linet Cherono. The CRC is composed of a clinical area including a central pharmacy that has the capacity to support both vaccine and therapeutic studies as well as provide additional non-study medicines for other non-study related care. The CRC laboratory is College of American Pathologist (CAP) accredited laboratory with a state-of-the-art Information Technology (IT) center that supports both HIV research and treatment programs. Both the CRC pharmacy and laboratory are approved by the National Institute of Allergy and Infectious Diseases/Division of AIDS (NIAID/DAIDS) to participate in DAIDS sponsored vaccine (Site # 1521) and therapeutics (Site #12501) studies. To support research, the Kericho CRC has a freezer farm equipped with liquid nitrogen plant and freezers for sample storage. The site has two fully equipped emergency rooms, with a standby ambulance to offer emergency response.</p>\n
      • other_details_explanation<p>\n Not applicable</p>\n
      • other_details_regulatory_notapproved<p>\n <span style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">We are only submitting to PPB.</span></p>\n
      • other_details_regulatory_approved<p>\n Not applicable</p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration2.5 years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorplacebo and control vacci
      • design_controlled_other_medicinalYes
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherYes
      • design_controlled_medicinal_specifyMenveo Verorab Infanrix
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites2
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site1. Kilifi (n=292)\nStep 1 (Safety cohort)= 124 \nStep 2 (dose-finding) =168\n2. Kericho (n=300)\nStep 2=300
      • total_participants_worldwide592
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • 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_consentYes
      • subjects_specifyWe will recruit young children (aged 2-5 years) and infants (8-10 months) who are not capable of giving consent.
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameMainga
      • investigator1_middle_name
      • investigator1_family_nameHamaluba
      • investigator1_qualificationMBChB MRCPCH MD
      • investigator1_professional_addressP.O.Box 230, Kilifi 80108, Kenya
      • investigator1_telephone(+254) 795 3204 22
      • investigator1_emailMHamaluba@kemri-wellcome.org
      • organisations_transferred_Yes
      • number_participantsExpected number of participants=592
      • notification
      • approval_date08-07-2019
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted20-02-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n This phase 1/2 trial multicentre, randomized controlled, double blind, trial is with two steps:</p>\n<p>\n -  step 1: a safety cohort conducted only at KEMRI-CGMRC site</p>\n<p>\n -  step 2: a dose-finding cohort conducted at both KEMRI-CGMRC and KEMRI/MRD-K sites.</p>\n<p>\n Safety of the Shigella4V vaccine was evaluated first in adults and subsequently in children and infants through an age-descending and dose escalation approach (safety cohort, step 1). Following confirmation of vaccine safety, further cohorts of infants (dose-finding cohort, step 2) were enrolled to evaluate immunogenicity of the vaccine at 4 different doses (4 ,12, 24, 48 μg) with/without adjuvant or control vaccines and expand safety data. A control vaccine was used, and participants were randomized at a ratio of 3:1 in adults, 2:1 in children, 2:1 in infants in step 1 and 8:1 in infants in step 2, to receive the candidate vaccine versus the control vaccine.</p>\n<p>\n Screening and enrollment for eligible participants into the safety cohort (step 1) of the trial was completed on 6^th November 2020 with a total number of 124 participants, including 16 adults (1 withdrawal), 48 children (1 withdrawal) and 60 infants (4 withdrawals) and they all completed the study visits and end of study.</p>\n<p>\n Adults were scheduled to have 7 clinic visits, children to have 10 clinic visits and infants to have 11 clinic visits. At selected visits, participants had blood drawn for the evaluation of safety and/or immunological parameters. All solicited and unsolicited adverse events (AEs), and medications for the first 7 days after each vaccination (day 0 – day 6) were collected and documented. Unsolicited AEs were collected for 28 days following each injection. In addition, from enrolment (1^st injection) through study termination, all serious adverse events (SAEs), all AEs leading to vaccine/study withdrawal, any AE medically relevant and associated concomitant medication, as well as any vaccination received were collected and recorded.</p>\n<p>\n Screening for eligible participants into the dose-finding cohort (step 2) commenced on 14^th December 2020 (Kericho site) and 17^th February 2021 (Kilifi site). Enrolment was completed on 2^nd August 2021 and 3^rd August 2021 at Kericho and Kilifi sites respectively with a combined total of 472 infants (341 infants at Kericho site and 131 infants at Kilifi site), including 74 withdrawals.</p>\n<p>\n All study vaccinations including the booster vaccinations, and all follow up visits were completed at both sites. The last participant last visit was conducted on 11^th November 2022 (Kericho site) and 14^th November 2022 (Kilifi site). The close-out monitoring visit was completed on 3^rd March 2023 (Kilifi) and 28 Feb 2023 (Kericho).</p>\n<p>\n Six protocol amendments were submitted to PPB during the study period and approval letters were received for all the submissions. The last protocol version 5.3 dated 23 Sep 2021 has approval letters from SERU and PPB dated 01 December 2021 and 17 February 2022 respectively.</p>\n<p>\n All protocol deviations and violation that occurred in the study were reported and uploaded onto the PPB portal. Response letters were received from SERU for all reported protocol deviations /violation.</p>\n<p>\n All safety data, including solicited and unsolicited AEs that were reported in the adults, children, and infant cohorts was evaluated by the data safety monitoring board (DSMB) and recommendation to proceed to the next stage and subsequently Step 2 of the study was provided by the DSMB. A total of six meetings to review the safety data were conducted by the DSMB and all six meetings had positive outcomes without concerns toward the safety data collected. All the DSMB safety data reports were submitted to PPB via the PPB clinical trials portal.</p>\n<p>\n A total of eight SAEs have occurred in the study, 5 at Kilifi site and 3 at Kericho site, and all were reported to PPB and SERU. All the SAEs were evaluated as not related to the investigational product and all have resolved. Also, one pregnancy was reported in a participant at Kilifi site that became pregnant (LMP 6^th January 2020) after she had missed her injectable contraceptive (Depo Provera) that was due in January 2020. The participant had completed her 2nd (last) vaccination visit on the 11^th October 2019 and was to have the end-of-study (final) visit on 27th March 2020, but this was disrupted as a result of the covid-19 pandemic. The pregnancy was uneventful, and delivery was at term on 20^th November 2020 with no complications reported. The infant was followed up until 6months of age, no complaints were reported by the mother, and baby remained in good condition. </p>\n<p>\n In conclusion, the studied vaccine candidate Shigella 4V was well tolerated in all formulations tested and did not raise any safety concerns. Shigella 4V elicited a robust humoral immune response against the vaccine antigens, independently if administered alone or in combination with the adjuvant, however combination of Shigella 4V with the adjuvant aluminium hydroxide increased immunogenicity to a larger extent post vaccination across all doses. The first two vaccinations elicited robust immune responses which was further amplified from the administration of a booster vaccination, especially 7 days post vaccination highlighting a potential priming effect provided by the first two vaccinations. The good safety profile combined with the robust immune response here reported for Shigella4V in the target population of young infants, provides the necessary information to advance development of this bioconjugate vaccine toward future phase III pivotal field studies.</p>\n
      • implication_results<p>\n The generation of the four valent vaccine and as well the results of the clinical study (S4V01) carry significant implications for the burden of diarrhoeal diseases found in LMICs, especially amongst children under the age of five. As the incidence of Shigellosis is highest in the 12-24 months age range, the target population used was 9-month-old infants. The safety and strong immunogenicity found following the vaccination will drive advancements in the development of this vaccine. There is no Shigella vaccine licensed to prevent shigellosis. The treatment options include antimicrobials, but the rise of antimicrobial resistance is concerning. The development of a Shigella vaccine is an important goal for public health and will have profound effects on the healthcare outcomes of the children within the LMICs most affected by Shigellosis. We anticipate that vaccination of the target population of 9 months infants will result in a measurable reduction in the burden of Shigellosis, with fewer cases, hospitalizations, and deaths attributable to the targeted illness.</p>\n<p>\n In summary, the implications of our vaccine study's achievements are far-reaching, with anticipated outputs and outcomes spanning licensure, disease prevention, healthcare outcomes, and healthcare policy. By leveraging our collaborative efforts and the support of future funding, we aim to realise these outcomes within the specified timelines, contributing to a healthier, more resilient future for communities in LMIC.</p>\n
      • quantity_importedProduct Name in vials and Quantity Received: S4V01 IMP (800); S4V01 IMP Diluent (1100); S4V01 IMP Adjuvant (500); Menveo (62); Verorab (100); Infanrix (35); Measles/ Rubella (114).
      • quantity_dispensedProduct Name in vials and Quantity dispensed: S4V01 IMP (538); S4V01 IMP Diluent (738); S4V01 IMP Adjuvant (297); Menveo (52); Verorab (95); Infanrix (20); Measles/ Rubella (110).
      • quantity_destroyedProduct Name in vials and Quantity destroyed: S4V01 IMP (262); S4V01 IMP Diluent (362); S4V01 IMP Adjuvant (183); Menveo (10); Verorab (5); Infanrix (15); Measles/ Rubella (0).
      • quantity_exportedProduct Name in vials and Quantity returned: S4V01 IMP (0); S4V01 IMP Diluent (0); S4V01 IMP Adjuvant (20 returned to Sponsor); Menveo (0); Verorab (0); Infanrix (0); Measles/ Rubella (4 returned to Kilifi County Hospital KEPI stores).
      • balance_siteThere is no balance left of any product.
      • final_date0000-00-00
      • modified2025-01-30 10:16:58
      • created2019-03-12 19:48:22
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id482
        • application_id773
        • given_nameMainga
        • middle_name
        • family_nameHamaluba
        • qualificationMBChB MRCPCH MD
        • professional_addressP.O.Box 230, Kilifi 80108, Kenya
        • telephone(+254) 795 3204 22
        • emailMHamaluba@kemri-wellcome.org
        • created2019-03-12 19:55:04
        • modified2020-02-20 05:20:18
      • 1(array)
        • id484
        • application_id773
        • given_nameKosgei
        • middle_name
        • family_nameJosphat
        • qualificationMBChB MSc DLSHTM
        • professional_addressWalter Reed Project Kericho, P.O. Box 1357, 20200
        • telephone+254 729 110 122
        • emailjosphat.kosgei@usamru-k.org
        • created2019-03-12 20:17:54
        • modified2020-02-20 05:20:18
    • SiteDetail(array)
      • 0(array)
        • id628
        • application_id773
        • county_id35
        • site_nameKEMRI-United States Army Medical Research Unit-Kenya, Kericho
        • physical_addressKericho
        • contact_detailsWalter Reed Project Kericho, P.O. Box 1357, 20200
        • contact_personJosphat Kosgei
        • site_capacity(null)
        • misc(null)
        • created2019-03-12 19:55:04
        • modified2020-02-20 05:20:18
        • County(array)
          • id35
          • county_nameKericho
          • created2012-06-15 10:26:16
          • modified2012-06-15 10:26:16
      • 1(array)
        • id630
        • application_id773
        • county_id3
        • site_nameKEMRI Wellcome Trust Research Program-CGMR-C
        • physical_addressKilifi
        • contact_detailsP.O.Box 230, Kilifi 80108, Kenya
        • contact_personMainga Hamaluba
        • site_capacity(null)
        • misc(null)
        • created2019-03-12 20:50:53
        • modified2020-02-20 05:20:18
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
    • Sponsor(array)
      • 0(array)
        • id376
        • application_id773
        • sponsorLimmaTech Biologics AG
        • sponsor_typeIndustry
        • contact_personCristina Alaimo
        • addressGrabenstrasse 3 8952 Schlieren Switzerland
        • telephone_number+41 (0)44 733 85 77
        • fax_number+41 44 733 85 74
        • cell_number+41 (0)79 386 72 28
        • email_addresscristina.alaimo@lmtbio.com
        • created2019-03-12 19:55:04
        • modified2020-02-20 05:20:18
  • 2(array)
    • Application(array)
      • id131
      • user_id70
      • trial_status_id5
      • abstract_of_study<p>\n  </p>\n<div>\n The RTS,S/AS01E candidate malaria vaccine is being developed for the routine immunization of infants and children living in malaria-endemic areas. The RTS,S/AS01E candidate malaria vaccine consists of sequences of the  ircumsporozoite (CS) protein and hepatitis B surface antigen (HBsAg) with the proprietary adjuvant AS01E (proprietary liposomes, MPL and Stimulon QS21 immunostimulants). The vaccine also induces a strong immune response against hepatitis B.</div>\n<div>\n In studies completed to date, the RTS,S candidate malaria vaccine adjuvanted with GSK’s proprietary Adjuvants  systems has consistently demonstrated efficacy in the pediatric population in malaria endemic countries. It has a favorable safety profile when given to young children and infants in co-administration with EPI routine vaccines.</div>\n<div>\n In order for the RTS,S candidate vaccine to be recommended for vaccination in children and infants in sub-Saharan Africa, safety of the vaccine needs to be demonstrated in HIV positive children, given the HIV disease burden in some parts of Africa.</div>\n<div>\n Approximately 2-3 million children live with HIV in sub- Saharan Africa; about 1500 children are newly infected each day.</div>\n<div>\n Vertical transmission rates are approximately 12-40%, and down to 2% in the context of optimal Prevention of Mother-to-Child Transmission (PMCT).</div>\n<div>\n Although HIV infected children have defective immunity and low immune response to some vaccines, the WHO recommends</div>\n<div>\n that children who are, or are s uspected of being, infected with HIV but are not yet symptomatic should be given all vaccines as recommended by the national EPI program. It is only the BCG and, where applicable, yellow fever vaccine - two live attenuated vaccines - that are contra-indicated in children with symptomatic</div>\n<div>\n HIV infection, because of the risk of disseminated invasive disease post vaccination. In all other situations, benefits of</div>\n<div>\n vaccination by far outweigh any associated risk. For non-live vaccines, HIV infection has not been shown to be associated with an increased risk of adverse vaccine-related event. On the contrary, because of HIV-infected children’s susceptibility towards infections, vaccination is strongly advocated.</div>\n<div>\n As HIV infected children are more susceptible to malaria they may potentially gain additional benefits from receiving the</div>\n<div>\n malaria candidate vaccine. Among HIV-infected children up to 5 years of age, rates of parasitemia and parasite densities are higher than in those without HIV. HIV-infected infants are also at increased risk for severe anemia and for hospitalization due to malaria. Furthermore, malaria episodes can transiently increase viral load, and thus could theoretically have an impact on HIV disease progression and HIV transmission.</div>\n<div>\n This study will assess the safety and immunogenicity of the RTS,S/AS01E candidate malaria vaccine in HIV-infected infants and children. It will also describe the malaria experience, HIV viral load and CD4+ cell count of subjects. Through the monitoring of markers of HIV disease progression we will determine whether a reduction of malaria attacks in these</div>\n<div>\n children translates to a lower rate of HIV disease progression.</div>\n<div>\n We will also be able to exclude a potential detrimental effect of the vaccine on HIV disease progression.</div>\n<div>\n The clinical development of the RTS,S candidate malaria vaccine is conducted under a partnership agreement with the PATH Malaria Vaccine Initiative (MVI) and is guided by a joint MVI/GSK Steering Committee.</div>\n<div>\n This study is overseen by a formally constituted IDMC operating under a charter.</div>\n<div>\n  </div>\n<div>\n <div>\n <u><strong>Detailed Title</strong></u></div>\n <div>\n A Phase III randomized, double blind (observer blinded), controlled study of the safety and immunogenicity of GlaxoSmithKline Biologicals’ candidate Plasmodium falciparum malaria vaccine RTS,S/AS01E (0.5 mL dose), administered IM according to a 0, 1, 2-month vaccination schedule in HIV infected infants and children living in a</div>\n <div>\n malaria-endemic region. Indication Primary immunization of HIV infected male and female infants</div>\n <div>\n and children (between and including 6 weeks and 17 months of age), if eligible according to inclusion and exclusion criteria.</div>\n <div>\n  </div>\n <div>\n <u><strong>Rationale for the study and study design</strong></u></div>\n <div>\n The RTS,S/AS01E candidate malaria vaccine is being developed for the routine immunization of infants and children</div>\n <div>\n living in malaria-endemic areas. The RTS,S/AS01E candidate malaria vaccine consists of sequences of the circumsporozoite (CS) protein and hepatitis B surface antigen (HBsAg) with the proprietary adjuvant AS01E (proprietary liposomes, MPL and Stimulon QS21 immunostimulants). The vaccine also induces a strong immune response against hepatitis B.</div>\n <div>\n In studies completed to date, the RTS,S candidate malaria vaccine adjuvanted with GSK’s proprietary Adjuvants Systems has consistently demonstrated efficacy in the pediatric population in malaria endemic countries. It has a favorable safety profile when given to young children and infants in co-administration with EPI routine vaccines.</div>\n <div>\n In order for the RTS,S candidate vaccine to be recommended for vaccination in children and infants in sub-Saharan Africa, safety of the vaccine needs to be demonstrated in HIV positive children, given the HIV disease burden in some parts of Africa.</div>\n <div>\n Approximately 2-3 million children live with HIV in sub- Saharan Africa; about 1500 children are newly infected each day.</div>\n <div>\n Vertical transmission rates are approximately 12-40%, and down to 2% in the context of optimal Prevention of Mother-to-Child Transmission (PMCT).</div>\n <div>\n Although HIV infected children have defective immunity and low immune response to some vaccines, the WHO recommends that children who are, or are suspected of being, infected with HIV but are not yet symptomatic should be given all vaccines as recommended by the national EPI program. It is only the BCG and, where applicable, yellow fever vaccine - two live attenuated vaccines - that are contra-indicated in children with symptomatic HIV infection, because of the risk of disseminated invasive disease post vaccination. In all other situations, benefits of vaccination by far  outweigh any associated risk. For non-live vaccines, HIV infection has not been shown to be associated with</div>\n <div>\n an increased risk of adverse vaccine-related event. On the contrary, because of HIV-infected children’s susceptibility</div>\n <div>\n towards infections, vaccination is strongly advocated. </div>\n <div>\n As HIV infected children are more susceptible to malaria they may potentially gain additional benefits from receiving the</div>\n <div>\n malaria candidate vaccine. Among HIV-infected children up to 5 years of age, rates of parasitemia and parasite densities are higher than in those without HIV. HIV-infected infants are also at increased risk for severe anemia and for hospitalization due to malaria. Furthermore, malaria episodes can transiently increase viral load, and thus could theoretically have an impact on HIV disease progression and HIV transmission. This study will assess the safety and immunogenicity of the RTS,S/AS01E candidate malaria vaccine in HIV-infected infants and children. It will also describe the malaria experience, HIV viral load and CD4+ cell count of subjects. Through the monitoring of markers of HIV disease progression we will determine whether a reduction of malaria attacks in these children translates to a lower rate of HIV disease progression. </div>\n <div>\n We will also be able to exclude a potential detrimental effect of the vaccine on HIV disease progression. The clinical development of the RTS,S candidate malaria vaccine is conducted under a partnership agreement with the PATH</div>\n <div>\n Malaria Vaccine Initiative (MVI) and is guided by a joint MVI/GSK Steering Committee. </div>\n <div>\n This study is overseen by a formally constituted IDMC operating under a charter.</div>\n <div>\n  </div>\n <div>\n <u><strong>Objectives</strong></u></div>\n <div>\n  </div>\n <div>\n <strong><em>Primary: Safety</em></strong></div>\n <div>\n ï‚· To describe the safety (occurrence of SAEs) of RTS,S/AS01E when administered on a 0, 1, 2-month schedule to</div>\n <div>\n HIV-infected infants and children, until 14 months post Dose 1.</div>\n <div>\n <em><strong>Secondary :Safety</strong></em></div>\n <div>\n ï‚· To describe the reactogenicity profile (occurrence of solicited symptoms) of RTS,S/AS01E when administered on a 0, 1, 2-month schedule to HIVinfected infants and children, during 7 days (day of vaccination and 6 subsequent days) after each vaccination.</div>\n <div>\n ï‚· To describe the safety (occurrence of unsolicited AEs) of RTS,S/AS01E when administered on a 0, 1, 2-month</div>\n <div>\n schedule to HIV-infected infants and children over a 30 day period after each vaccination.</div>\n <div>\n ï‚· To describe the occurrence of non-malaria-related SAEs in HIV infected infants and children vaccinated with RTS,S/AS01E when  dministered on a 0, 1, 2-month schedule, until 14 months post Dose 1.</div>\n <div>\n Immunogenicity</div>\n <div>\n ï‚· To assess the antibody responses to CS and  HBs antigens for RTS,S/AS01E when administered on a 0, 1, 2-month schedule to HIV-infected infants and children up to 12 months post Dose 3.</div>\n <div>\n Malaria monitoring</div>\n <div>\n ï‚· To monitor and describe the occurrence of   malaria disease in HIV infected infants and children occurring during the study period.</div>\n <div>\n <em><strong>Progression of HIV disease</strong></em></div>\n <div>\n ï‚· To describe the evolution of CD4+ cell counts (CD4 % and absolute counts), HIV viral load and HIV WHO clinical classification for  RTS,S/AS01E when administered on a 0, 1,</div>\n <div>\n 2-month schedule to HIV-infected infants and children up to 14 months post Dose 1.</div>\n <div>\n <em><strong>Growth</strong></em></div>\n <div>\n To describe growth in HIV infected infants and children during the study period.</div>\n <div>\n Study design ï‚· Experimental design: Phase III, double blind (observer blind), randomized (1:1 ratio) controlled trial with two groups, one vaccinated with the experimental malaria</div>\n <div>\n candidate vaccine RTS,S/AS01E, the other one with the rabies control vaccine.</div>\n <div>\n ï‚· Parents/Legally Acceptable Representatives (LARs) of HIV-infected infants and children will be identified at HIV clinics and will be informed about the study. If interested, and if the infant/child is eligible based on the inclusion and</div>\n <div>\n exclusion criteria, the parents/LARs will be asked to consent for study participation.</div>\n <div>\n ï‚· Route of vaccine administration: intramuscular (IM) route in the left antero-lateral thigh for infants < 5 months and left deltoid for infants/children  5 months of age.</div>\n <div>\n ï‚· The experimental vaccines will be given outside the context of co-administration with other vaccines. Standard EPI vaccine delivery will be allowed 1 week apart from study vaccines.</div>\n <div>\n <div>\n ï‚· Each subject will be observed for at least 60 minutes after vaccination to evaluate and treat any acute adverse events (AEs).</div>\n <div>\n ï‚· There will be a 7-day follow-up period for solicited AEs post-vaccination. Day 0 evaluation will be carried out by the study clinician at the study center. Subsequently, trained field workers will visit the infants and children to solicit AEs on Days 1 to 5 after each vaccination.</div>\n <div>\n Evaluation on Day 6 post vaccination which will be carried out by the study clinician at the study center.</div>\n <div>\n ï‚· There will be a 30-day (day of vaccination and 29 subsequent days) follow-up after each vaccine dose for reporting unsolicited symptoms.</div>\n <div>\n ï‚· SAEs will be recorded throughout the study period. Prior to vaccination, any SAE due directly to study procedures will be recorded. All SAEs will be recorded beginning with the administration of the first dose and ending 14 months after the first dose of study vaccine. Monthly clinic visits will contribute to maximal capture of SAEs.</div>\n <div>\n ï‚· Safety blood samples for assessment of hematology, hepatic and renal function will be collected at baseline, 6 days post Dose 1, one month post Dose 3, 6 months post Dose 3 and 12 months post Dose 3. (Amended 26 January 2011).</div>\n <div>\n ï‚· IDMC reports:</div>\n <div>\n Safety reports will be sent at three time points after 30 subjects have completed the 7 days of follow-up post Dose</div>\n <div>\n 1, post Dose 2 and post Dose 3. The IDMC will review the data to authorize continuation of enrolment and</div>\n <div>\n vaccinations.</div>\n <div>\n ï‚· Long-lasting insecticide impregnated bednets and directions for use will be distributed at screening, regardless of the decision of parents/LARs to participate in the study or not. </div>\n <div>\n ï‚· Children and infants will be followed passively for the occurrence of clinical malaria for the duration of their participation in the study. Cases will be detected at all</div>\n <div>\n study health facilities.</div>\n <div>\n ï‚· P. falciparum parasitemia will be determined on a crosssectional sample in all study participants at study end (Month 14).</div>\n <div>\n ï‚· This study will be conducted in the context of access to an HIV management unit with availability of Voluntary Counseling and Testing (VCT),pediatric Highly Active Antiretroviral Therapy (HAART), daily  trimethoprimsulfamethoxasole prophylaxis (co-trimoxazole: CTX) for the prevention of opportunistic infections, Prevention of Mother-to-Child Transmission (PMCT) and HIV clinical follow up, including immunology monitoring, according to the national HIV control guidelines. CTX prophylaxis and antiretroviral therapy</div>\n <div>\n (ART) will be monitored during the trial.</div>\n <div>\n ï‚· Subjects with Grade III or IV AIDS, with an acute illness resulting in deferment of vaccination past the 30-day window, or with an abnormal laboratory value at the time of enrolment will not be able to participate in the study  (see exclusion criteria). However, in case the health of the subject improves, he or she might be re-onsidered</div>\n <div>\n for enrolment. In that case, a new ICF should be signed and all screening procedures should be repeated, except possibly the HIV DNA PCR test. (Amended 26 January 2011).</div>\n <div>\n ï‚· There will be a balanced randomization to ensure that both groups are comparable in terms of age and CD4 %</div>\n <div>\n levels. An equivalent number of children of age categories 6 weeks to 4 months and 5 months to 17 months, and with various CD4 % levels (<10%, 10-14%, 15-19%, 20%) will be enrolled in both study groups. Children can be enrolled whether or not they are on ART at enrollment. However all enrolled children will be provided ART and daily septrin, according to national guidelines.</div>\n <div>\n ï‚· Data collection: this study will use electronic case report forms (eCRF) by remote data entry (RDE).</div>\n <div>\n ï‚· Study duration will be approximately 14 months per subject. </div>\n <div>\n ï‚· The final analysis of the study will be conducted on all data collected up to Month 14 (Clinic Visit 19).</div>\n <div>\n <em><strong>Number of subjects </strong></em></div>\n <div>\n 200 infants and children aged 6 weeks to 17 months will be</div>\n <div>\n enrolled.</div>\n <div>\n <em><strong>Primary endpoint :Safety</strong></em></div>\n <div>\n ï‚· Serious adverse events Occurrence of SAEs from the time of first vaccination until 14 months post Dose 1.</div>\n <div>\n <div>\n <em><strong>Secondary endpoints Safety</strong></em></div>\n <div>\n ï‚· Solicited local and general symptoms Occurrence of general and local solicited symptoms over a 7-day follow-up period (day of vaccination and 6 subsequent days) after each vaccination.</div>\n <div>\n ï‚· Unsolicited adverse events Occurrence of unsolicited symptoms over a 30-day followup period (day of vaccination and 29 subsequent days) after each vaccination.</div>\n <div>\n ï‚· Non-malaria-related serious adverse events Occurrence of non-malaria-related SAEs from the time of first vaccination until 14 months post Dose 1.</div>\n <div>\n <em><strong>Immunogenicity</strong></em></div>\n <div>\n ï‚· Immunogenicity of a primary course of investigational vaccine Anti-CS antibody titers prior to vaccination and one month post Dose 3.</div>\n <div>\n Anti-HBs antibody titers prior to vaccination and one month post Dose 3.</div>\n <div>\n Anti-CS antibody titers at 12 months post Dose 3.</div>\n <div>\n Anti-HBs antibody titers at 12 months post Dose 3.</div>\n <div>\n <em><strong>Malaria monitoring</strong></em></div>\n <div>\n ï‚· Malaria disease:Occurrence of malaria disease according to specific case definitions.</div>\n <div>\n ï‚· Malaria parasitemia:Asexual P. falciparum parasitemia prevalence and density at 12 months post Dose 3. Progression of HIV disease</div>\n <div>\n ï‚· HIV viral load:Viral load (copies/mL) at baseline and at 1 month, 6 months and 12 months post Dose 3.</div>\n <div>\n ï‚· T-cell counts CD4+ % and absolute cell counts at baseline and at 1 month, 6 months and 12 months post Dose 3. </div>\n <div>\n ï‚· HIV clinical classification progression:WHO HIV clinical classification at baseline, 1 month, 6 months and 12 months post Dose 3.</div>\n <div>\n <em><strong>Growth</strong></em></div>\n <div>\n ï‚· Growth parameters:Weight, age/length and middle upper arm circumference for age score at baseline and study end.</div>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • study_title<p>\n SAFETY AND IMMUNOGENICITY STUDY OF GSK BIOLOGICALS' <em>Plasmondium falciparum </em>MALARIA VACCINE 257049 ADMINISTERED TO HIV INFECTED INFANTS AND CHILDREN</p>\n
      • laymans_summary(null)
      • short_titleMAL-58 Study: Protocol no. 112745: SAFETY AND IMMUNOGENICITY STUDY OF GSK BIOLOGICALS\' Plasmondium falciparum MALARIA VACCINE 257049 ADMINISTERED TO HIV INFECTED INFANTS AND CHILDREN
      • protocol_noECCT/09/09/02
      • version_noFINAL PROTOCOL
      • date_of_protocol11-08-2009
      • study_drugRTS,S/AS01E
      • disease_conditionMALARIA
      • 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
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressHarun.N.Aketch@gsk.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantHARUN NJAGO AKETCH
      • declaration_date121-05-2013
      • declaration_principal_investigator DECLARATION BY PRINCIPAL INVESTIGATOR Name: Title of the study: A Phase III randomized, double blind (observer blinded), controlled study of the safety and immunogenicity of GlaxoSmithKline Biological’ candidate Plasmodium falci
      • declaration_date216-07-2013
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n  </p>\n<div>\n ï‚· A male or female infant or child between and including 6 weeks to 17 months of</div>\n<div>\n age, at the time of first vaccination.</div>\n<div>\n ï‚· Signed or thumb-printed informed consent obtained from the parent(s)/LAR(s)</div>\n<div>\n of the infant or child. Where parents/LARs are illiterate, the consent form will</div>\n<div>\n be countersigned by a witness.</div>\n<div>\n ï‚· Subjects who the investigator believes that their parents/LARs can and will</div>\n<div>\n comply with the requirements of the protocol should be enrolled in the study.</div>\n<div>\n ï‚· Subjects who are known to be HIV-infected (documented positive DNA PCR),</div>\n<div>\n whether taking HIV antiretroviral treatment (ART) or not.</div>\n<div>\n ï‚· Subjects who are born following a normal gestation period (i.e. gestation period</div>\n<div>\n of minimum 36 weeks and maximum 42 weeks).</div>\n
      • principal_exclusion_criteria<p>\n  </p>\n<div>\n ï‚· Acute disease at the time of enrolment (acute disease is defined as the presence</div>\n<div>\n of a moderate or severe illness with or without fever). However, the presence of</div>\n<div>\n an illness listed as Grade I or Grade II (WHO pediatric AIDS clinical staging;</div>\n<div>\n see Appendix B) will not of itself constitute an exclusion criterion. Enrolment</div>\n<div>\n should be deferred if axillary temperature is  37.5°C.</div>\n<div>\n ï‚· Grade III or Grade IV abnormality on screening laboratory blood sample (see</div>\n<div>\n Table 7).</div>\n<div>\n ï‚· Grade III or IV AIDS at the time of enrolment (WHO pediatric AIDS clinical</div>\n<div>\n staging; see Appendix B).</div>\n<div>\n ï‚· Major congenital defects.</div>\n<div>\n ï‚· Planned administration/administration of a vaccine not foreseen by the study</div>\n<div>\n protocol prior to or within 7 days of study vaccine.</div>\n<div>\n ï‚· Use of any investigational or non-registered product (drug or vaccine) other than</div>\n<div>\n the study vaccine 30 days preceding Dose 1 of study vaccine, or planned use</div>\n<div>\n during the study period.</div>\n<div>\n ï‚· Previous participation in any other malaria vaccine trial.</div>\n<div>\n ï‚· Simultaneous participation in another clinical trial including administration of</div>\n<div>\n experimental treatment.</div>\n<div>\n ï‚· Same sex twins.</div>\n<div>\n ï‚· History of allergic reactions (significant IgE-mediated events) or anaphylaxis to</div>\n<div>\n previous immunizations.</div>\n<div>\n <div>\n History of allergic disease or reactions likely to be exacerbated by any</div>\n <div>\n component of the study vaccine.</div>\n <div>\n ï‚· Child in care.</div>\n</div>\n<p>\n  </p>\n
      • primary_end_points<p>\n  </p>\n<div>\n Safety</div>\n<div>\n ï‚· To describe the safety (occurrence of SAEs) of RTS,S/AS01E when administered on a 0, 1, 2-month schedule to</div>\n<div>\n HIV-infected infants and children, until 14 months post Dose 1.</div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifySAFETY AND IMMUNOGENICITY
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifySafety and immunogenicity, Phase 3
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n -</p>\n
      • other_details_explanation<p>\n THIS TRIAL IS CONDUCTED IN KENYA SINCE THE PRESENCE AND PREVALENCE OF MALARIA HAS BEEN NOTED TO BE HIHG HERE AND NOT THE APPLICANT'S /SPONSOR HOST COUNTRY. </p>\n
      • other_details_regulatory_notapproved<p>\n NONE</p>\n
      • other_details_regulatory_approved<p>\n NONE</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration200
      • 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_comparatorRABIES VACCINE
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • 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_countriesNo
      • multiple_member_states
      • number_of_sites2
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteONE HUNDRED PARTICIPANTS PER SITE
      • total_participants_worldwide200
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_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_nameBERNHARD
      • investigator1_middle_name
      • investigator1_family_nameOGUTU
      • investigator1_qualificationMBCHB,MMED,PAED
      • investigator1_professional_addressKEMRI/Walter Reed Project, P.O. Box 54-40100, kISUMU
      • investigator1_telephone+254-57-22942
      • investigator1_emailbogutu@wrp-ksm.org
      • organisations_transferred_No
      • number_participantsTWO HUNDRED
      • notification
      • approval_date24-06-2010
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted19-07-2013
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2018-07-10 15:46:31
      • created2013-04-30 14:35:52
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id79
        • application_id131
        • given_nameLUCAS
        • middle_nameOTIENO
        • family_nameTINA
        • qualificationMBCHB MPH,
        • professional_addressKEMRI/Walter Reed Project, P.O. Box 54-40100, kISUMU
        • telephone+254-57-22942
        • emailotienol@wrp-ksm.org
        • created2013-04-30 14:50:01
        • modified2013-07-19 16:25:12
      • 1(array)
        • id80
        • application_id131
        • given_nameMARY
        • middle_name
        • family_nameHAMEL
        • qualificationMD,INTERNAL MED.
        • professional_address+254-57-22923
        • telephoneKEMRI-CDC RESEARCH STATION, KISIAN, KISUMU BUSIA ROAD
        • emailmlh8@cdc.gov
        • created2013-04-30 15:32:27
        • modified2013-07-19 16:25:12
    • SiteDetail(array)
      • 0(array)
        • id100
        • application_id131
        • county_id41
        • site_nameKEMRI-CDC,
        • physical_addressKEMRI-CDC RESEARCH STATION,KISIAN,KISUMU-BUSIA ROAD
        • contact_detailsP O Box 1578-40100,KISUMU;TEL +254-57-22923
        • contact_personDR. MARY HAMEL
        • site_capacity(null)
        • misc(null)
        • created2013-04-30 14:50:01
        • modified2013-07-19 16:25:12
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 1(array)
        • id101
        • application_id131
        • county_id42
        • site_nameKEMRI-WRP
        • physical_addressNEXT TO NEW NYANZA PROVINCIAL GENERAL HOSPITAL,KONDELE ,KISUMU
        • contact_detailsWalter Reed Project, Kombewa Clinical Research Center. P.0.Box 54-40100, Kisumu, Kenya , Tel:+254-57-2022942
        • contact_personDR. LUCAS OTIENO
        • site_capacity(null)
        • misc(null)
        • created2013-04-30 15:50:10
        • modified2013-07-19 16:25:12
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id62
        • application_id131
        • sponsorGlaxosmithkline
        • sponsor_type(null)
        • contact_personHarun Njago Aketch
        • address78392-00507
        • telephone_number+254 20 6933200/314
        • fax_number
        • cell_number+254 725669143
        • email_addressHarun.N.Aketch@gsk.com
        • created2013-04-30 14:50:01
        • modified2013-07-19 16:25:12
  • 3(array)
    • Application(array)
      • id858
      • user_id71
      • trial_status_id7
      • abstract_of_study<p>\n This is a Phase 1/2 study to evaluate the safety and tolerability of two broadly neutralizing monoclonal human antibodies (bNAbs), 3BNC117-LS-J, which targets the CD4 binding site on HIV-1 envelope protein, and 10-1074-LS-J which targets the V3 loop of HIV-1 envelope protein. The hypothesis is that the two antibodies will be safe for healthy American and African adults when co-administered subcutaneously or intravenously and, after subcutaneous administration in the optimal ratio, each antibody will maintain trough serum levels >10 µg/ml at steady state. Primary Objectives 1.To evaluate the safety and tolerability of two broadly neutralizing monoclonal human antibodies, 3BNC117-LS-J and 10-1074-LS-J, when given alone and in combination, intravenously (IV) or subcutaneously (SC) to healthy American and African adults. 2.To evaluate the pharmacokinetic profile of two broadly neutralizing monoclonal human antibodies, 3BNC117-LS-J and 10-1074-LS-J, when given alone or in combination, IV or SC to healthy American and African adults. 3.To identify a regimen of the two antibodies that, when given SC every 3 months, will maintain a trough level of > 10 µg/ml for each antibody in >80% of study population. Secondary Objectives 1.To evaluate the effect of participant characteristics (e.g. sex, body weight or body mass index ) on pharmacokinetic parameters. 2.To conduct pharmacokinetic modelling to assess the effect of dose, dose ratio, dosing frequency and loading dose on serum trough levels of each antibody. 3.To assess the incidence and titers of anti-drug antibodies (ADA) against each antibody</p>\n
      • study_title<p>\n Safety and Pharmacokinetics of the Combination Broadly Neutralizing Antibodies, 3BNC117-LS-J and 10-1074-LS-J, in Healthy American and African Adults</p>\n
      • laymans_summary<p>\n This is a clinical research study in which 2 experimental study products either given separately or together are being tested to see if they are safe, and to understand how long they stay in the human body. We hope to learn what kind of side effects one may experience after receiving the study product(s). The two study products being tested are called 3BNC117-LS-J and 10-1074-LS-J. They are human antibodies against HIV that have been made in a laboratory. HIV is the virus that causes Acquired Immunodeficiency Syndrome (AIDS). Scientists are hoping that one day, these antibodies can be used to help prevent HIV infection in people</p>\n
      • short_titleIAVI C100
      • protocol_noECCT/20/06/01
      • version_noVersion 2.0
      • date_of_protocol13-12-2019
      • study_drug3BNC117-LS-J and 10-1074-LS-J
      • disease_conditionHIV
      • 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
      • 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
      • 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_impd0
      • 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_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan0
      • applicant_contractual_agreement0
      • declaration_applicantProf Walter Jaoko
      • declaration_date104-06-2020
      • declaration_principal_investigatorN/A
      • declaration_date204-06-2020
      • placebo_presentYes
      • study_objectives<p>\n Primary Objectives 1. To evaluate the safety and tolerability of two broadly neutralizing monoclonal human antibodies, 3BNC117-LS-J and 10-1074-LS-J, when given alone and in combination, intravenously (IV) or subcutaneously (SC) to healthy American and African adults. 2. To evaluate the pharmacokinetic profile of two broadly neutralizing monoclonal human antibodies, 3BNC117-LS-J and 10-1074-LS-J, when given alone or in combination, IV or SC to healthy American and African adults. 3. To identify a regimen of the two antibodies that, when given SC every 3 months, will maintain a trough level of > 10 µg/ml for each antibody in >80% of study population. Secondary Objectives 1. To evaluate the effect of participant characteristics (e.g. sex, body weight or body mass index ) on pharmacokinetic parameters. 2. To conduct pharmacokinetic modelling to assess the effect of dose, dose ratio, dosing frequency and loading dose on serum trough levels of each antibody. 3. To assess the incidence and titers of anti-drug antibodies (ADA) against each antibody</p>\n
      • principal_inclusion_criteria<p>\n INCLUSION CRITERIA 1. Healthy male and female individuals, as assessed by a medical history, physical exam, and laboratory tests 2. At least 18 years of age on the day of screening and have not reached their 46th birthday on the day of the first administration 3. Willing to undergo HIV testing, risk reduction counseling and receive HIV test results; committed to maintaining low-risk behavior for the trial duration 4. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study; 5. In the opinion of the Principal Investigator or designee and based on Assessment of Understanding results, has understood the information provided and potential impact and/or risks linked to investigational product administration and participation in the trial; written informed consent will be obtained from the participant before any study-related procedures are performed; 6. All male and female participants of reproductive potential who are engaging in sexual activity that could lead to pregnancy must commit to use an effective method of contraception from enrolment until 9months after last administration. 7. All participants born female and of reproductive potential who are not heterosexually active at screening must agree to utilize an effective method of contraception if they become heterosexually active as outlined above. 8. All participants born female and of reproductive potential must be willing to undergo urine pregnancy tests at time points indicated in the Schedule of Procedures 9. Willing to forgo donations of blood, or any other tissues during the study and, for those who test HIV-positive due to antibody-induced seropositivity, until the anti-HIV antibody titers become undetectable on HIV tests used in the community</p>\n
      • principal_exclusion_criteria<p>\n EXCLUSION CRITERIA 1. Confirmed HIV infection 2. Reported risk for HIV infection within 6months prior to investigational product administration as specified by the protocol 3. Any clinically relevant abnormality on history or examination, including history of immunodeficiency or autoimmune disease; use of systemic corticosteroids (the use of topical or inhaled steroids is permitted), immunosuppressive, anticancer, anti-tuberculosis or other medications considered significant by the investigator within the previous 6 months. Limited exceptions are permitted and are described in detail in the protocol. 4. Any clinically significant acute or chronic medical condition that is considered progressive or in the opinion of the investigator makes the participant unsuitable for participation in the study 5. Asthma that is not well controlled 6. If female, pregnant or planning a pregnancy during the study period of enrolment until 9months after final IP administration; or lactating 7. Bleeding disorder diagnosed by a physician (e.g., factor deficiency, coagulopathy or platelet disorder that requires special precautions) 8. History of splenectomy 9. Any of the following abnormal hematological, chemistry and urine laboratory parameters as detailed in the protocol 10. Infectious disease diagnosis: • Hepatitis B infection as measured by HbsAg and/or PCR • Hepatitis C infection Africa: HCV Ab positive and/or PCR; • Active syphilis (positive RPR confirmed by TPHA) 11. Receipt of blood transfusion or blood-derived products within the previous 3 months 12. Participation in another clinical trial of an investigational product currently, within the previous 3 months or expected participation during this study 13. Prior receipt of any investigational HIV vaccine candidate, or HIV monoclonal antibody, 14. History of severe local or systemic reactions to blood or immunoglobulin products or constituents of investigational product (e.g., anaphylaxis, respiratory difficulties, angioedema) 15. Psychiatric condition that compromises safety of the participant and precludes compliance with the protocol. 16. Seizure disorder: A participant who has had a seizure in the last 3 years is excluded. 17. History of malignancy in the past 5 years or ongoing malignancy 18. Body mass index (BMI) >40 19. Active tuberculosis 20. If, in the opinion of the Principal Investigator, it is not in the best interest of the participant to participate in the trial</p>\n
      • primary_end_points<p>\n Primary:</p>\n<p>\n Safety and Tolerability: 1. Proportion of participants with solicited and IP-related unsolicited adverse events that are Grade 2 and above (including confirmed laboratory abnormalities) and their duration. 2. Proportion of participants with solicited and IP-related unsolicited adverse events that are Grade 3 and above (including confirmed laboratory abnormalities) and their duration. 3. Proportion of participants with serious adverse events (SAEs) throughout the study period that are considered related to investigational product and their duration. Pharmacokinetics (PK) 4. The ratio of 3BNC117-LS-J to 10-1074-LS-J that, when injected SC, will maintain similar levels of each bNAb at steady state.</p>\n<p>\n Secondary: 1. Serum concentration of the bNAb in each group at multiple timepoints along with participant characteristics (e.g. sex, weight, and BMI). 2. Serum concentration of 3BNC117-LS-J and 10-1074-LS-J in each group at multiple timepoints along with dose, dose ratio, dosing frequency and loading dose. 3. Serum concentration of anti-3BNC117-LS-J and anti-10-1074-LS-J antibodies in each group at multiple timepoints.</p>\n<p>\n Exploratory: 1. Serum concentration of the bNAb in each group at multiple timepoints along with geographical region, immunoglobulin levels and the subcutaneous site of injection (abdomen vs. arm). 2. Magnitude of serum neutralization of virus isolates sensitive to each antibody at 7 days and 12 weeks after SC administration in selected participants in America and Africa. 3. Proportion of participants with reduction in bNAb half-life concomitant with ADA. 4. Proportion of participants with reduction in bNAb neutralization potency concomitant with ADA. 5. Proportion of participants with pIMDs throughout the study period that are considered related to investigational product and their duration. 6. Relationship of solicited and unsolicited adverse events and pIMDs to ADA. 7. bNAb concentrations in mucosal secretions at selected sites.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong>Number of Staff:</strong> 1 physician, I pharmacist, 2 pharmacy staff, 2 trial clinicians, 3 nurse counselors, 2 community staff, 1 data IT/Data manager, 3 Data staff and 8 lab staff, I labaratory Manager</p>\n<p>\n <strong>Core Staff:</strong></p>\n<p>\n 1. Prof. Omu Anzala MBChB PhD, Co-Investigator,Virologist & Senior Research Scientist 2. Dr. Marianne Mureithi PhD, C100 Mucosal Study team leader 3. Dr Moses Masika MBChB MSc.Laboratory Manager 4.  Ms. Hilda Ogutu BsN, KPHN, KRM,KRN,Study Coordinator 6. Jacquelyn Nyange RN, BA, MSc. Clinical PSY Regulatory compliance</p>\n<p>\n <strong>Site Facities</strong>: Clinic, Labaratory, data and  Pharmacy  space available on site</p>\n<p>\n <strong>Emergency Facities:</strong> 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/A</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_comparatorPlacebo
      • design_controlled_other_medicinalYes
      • 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_states1
      • number_of_sites2
      • multi_country_listKenya \nUSA\nRwanda\nUganda\nSouth Africa
      • data_monitoring_committeeYes
      • total_enrolment_per_site24
      • total_participants_worldwide225 HIV-uninfected participants
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultNo
      • 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_nameN/A
      • investigator1_middle_nameN/A
      • investigator1_family_nameN/A
      • investigator1_qualificationN/A
      • investigator1_professional_addressN/A
      • investigator1_telephoneN/A
      • investigator1_emailgmutua@kaviuon.org
      • organisations_transferred_No
      • number_participants24
      • notification
      • approval_date02-12-2020
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted07-12-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApplication approved by the expert committee
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-04-02 09:06:41
      • created2020-03-06 10:44:03
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id528
        • application_id858
        • given_nameProf Walter Jaoko
        • middle_nameGodfrey
        • family_nameJaoko
        • qualificationMBChB, MTropMed, PhD, PGD (Health Research Ethics)
        • professional_addressP.O Box 19676
        • telephone0727555254
        • emailwjaoko@kaviuon.org
        • created2020-03-06 11:27:32
        • modified2021-12-07 12:35:37
    • SiteDetail(array)
      • 0(array)
        • id703
        • application_id858
        • county_id47
        • site_nameKAVI-Insitute of Clinical Research, KNH site
        • physical_addressCollege of health Sciences, University of Nairobi, Kenyatta National Hospital
        • contact_detailsP.O Box 19676, 00202 KNH
        • contact_personDr Gaudensia Nzembi Mutua
        • site_capacity(null)
        • misc(null)
        • created2020-03-06 11:27:32
        • modified2021-12-07 12:35:37
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id415
        • application_id858
        • sponsorInternational AIDS Vaccine Initiative (IAVI)
        • sponsor_typeOthers
        • contact_personDagna Laufer, MD
        • address125 Broad Street, 9th Floor
        • telephone_number+1 212-328-7459
        • fax_numberN/A
        • cell_number+1 212-328-7459
        • email_addressdlaufer@iavi.org
        • created2020-03-06 11:27:32
        • modified2021-12-07 12:35:37
  • 4(array)
    • Application(array)
      • id425
      • user_id613
      • trial_status_id7
      • abstract_of_study<p>\n The Human Immunodeficiency Virus (HIV) epidemic presents the most serious infectious<br />\n disease threat worldwide. The global incidence of new human immunodeficiency virus (HIV)<br />\n infections peaked in the mid-1990s, and a reduction in this incidence has been observed. In 2012<br />\n there were 2.3 million new cases, down from 3.4 million in 2001. The reduction of HIV<br />\n incidence is due to multiple factors that include prevention and treatment programs. The wider<br />\n availability of antiretroviral therapy (ART), prevention of mother-to-child transmission<br />\n programs, and a diverse array of other interventions have all contributed to turning the tide of the<br />\n epidemic. Long-term use of antiretroviral therapy (ART) in HIV-positive persons may be<br />\n challenged by the need for high-level life long adherence to a daily regimen, development of<br />\n drug resistance and cross-resistance, short and long-term toxicities, and cost. Administration of<br />\n broadly neutralizing monoclonal antibodies has the potential to treat HIV infection by preventing<br />\n viral spread, by facilitating clearance of virus particles and mediating destruction of virusproducing<br />\n cells. This may decrease the viral reservoir and limit chronic immune activation. This<br />\n is a multi-centre, double-blinded, placebo-controlled study of the safety and impact of broadly<br />\n neutralizing monoclonal antibody therapy with VRC01 on viremia in acute HIV infection, alone<br />\n or in combination with antiretroviral therapy (ART). A total of twenty four participants will be<br />\n enrolled, with Kericho site enrolling about six participants. Participants will be randomized to<br />\n three groups; 1, 2 and 3. Group 1 will receive immediate ART only (n=8), Group 2 will receive<br />\n immediate ART and mAb therapy (n=8) and Group 3 will receive immediate mAb therapy and<br />\n subsequent ART from day 7 (n=8). Other sites participating include Uganda, Tanzania and<br />\n Thailand. Participants from the RV217 High Risk Cohort study who become acutely infected<br />\n with HIV will be screened and enrolled into this study. The study duration is 25 weeks. Results<br />\n obtained from this study may inform considerations for the development of broadly neutralizing<br />\n monoclonal antibodies for use in therapeutic settings.</p>\n
      • study_title<p>\n Safety  and  Virologic Effect  Of  A  Human   Monoclonal   Antibody,   VRC-HIVmAb060-00-Ab  (VRCOl),   With Broad  HIV-1  Neutralizing Activity, Administered Intravenously to Adults  During Early Acute HIV Infection.</p>\n
      • laymans_summary<div>\n The Human Immunodeficiency Virus (HIV) epidemic presents the most serious infectious</div>\n<div>\n disease threat worldwide. The global incidence of new human immunodeficiency virus (HIV)</div>\n<div>\n infections peaked in the mid-1990s, and a reduction in this incidence has been observed. In 2012</div>\n<div>\n there were 2.3 million new cases, down from 3.4 million in 2001. The reduction of HIV</div>\n<div>\n incidence is due to multiple factors that include prevention and treatment programs. The wider</div>\n<div>\n availability of antiretroviral therapy (ART), prevention of mother-to-child transmission</div>\n<div>\n programs, and a diverse array of other interventions have all contributed to turning the tide of the</div>\n<div>\n epidemic. Long-term use of antiretroviral therapy (ART) in HIV-positive persons may be</div>\n<div>\n challenged by the need for high-level life long adherence to a daily regimen, development of</div>\n<div>\n drug resistance and cross-resistance, short and long-term toxicities, and cost. Administration of</div>\n<div>\n broadly neutralizing monoclonal antibodies has the potential to treat HIV infection by preventing</div>\n<div>\n viral spread, by facilitating clearance of virus particles and mediating destruction of virusproducing</div>\n<div>\n cells. This may decrease the viral reservoir and limit chronic immune activation. This</div>\n<div>\n is a multi-centre, double-blinded, placebo-controlled study of the safety and impact of broadly</div>\n<div>\n neutralizing monoclonal antibody therapy with VRC01 on viremia in acute HIV infection, alone</div>\n<div>\n or in combination with antiretroviral therapy (ART). A total of twenty four participants will be</div>\n<div>\n enrolled, with Kericho site enrolling about six participants. Participants will be randomized to</div>\n<div>\n three groups; 1, 2 and 3. Group 1 will receive immediate ART only (n=8), Group 2 will receive</div>\n<div>\n immediate ART and mAb therapy (n=8) and Group 3 will receive immediate mAb therapy and</div>\n<div>\n subsequent ART from day 7 (n=8). Other sites participating include Uganda, Tanzania and</div>\n<div>\n Thailand. Participants from the RV217 High Risk Cohort study who become acutely infected</div>\n<div>\n with HIV will be screened and enrolled into this study. The study duration is 25 weeks. Results</div>\n<div>\n obtained from this study may inform considerations for the development of broadly neutralizing</div>\n<div>\n monoclonal antibodies for use in therapeutic settings.</div>\n
      • short_titleVRC01 Monoclonal HIV Antibodies Study
      • protocol_noECCT/15/10/01
      • version_no2.0
      • date_of_protocol29-04-2015
      • study_drugVRC01 Monoclonal Antibodies
      • disease_conditionHIV
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameNormal Saline
      • comparator_registeredYes
      • comparator_countriesKenya
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjosphat.kosgei@usamru-k.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_countries1
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd0
      • applicant_prev_data0
      • applicant_stability_data0
      • applicant_analysis_cert0
      • applicant_pictorial_sample0
      • applicant_gcp_training0
      • applicant_dsmb_charter0
      • applicant_detailed_budget0
      • applicant_indemnity_pi0
      • applicant_practice_license0
      • applicant_registration_ctr(null)
      • applicant_pan_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist0
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr josphat Kosgei
      • declaration_date108-10-2015
      • declaration_principal_investigatorDr Josphat Kosgei
      • declaration_date208-10-2015
      • placebo_presentYes
      • study_objectives<div>\n PRIMARY OBJECTIVES</div>\n<div>\n 1. Safety of VRC01 in acutely HIV-infected viremic individuals</div>\n<div>\n 2. Impact of VRC01 on plasma viremia in each mAb arm compared to the ART plus</div>\n<div>\n placebo control at day 7 (+/- 1 day)</div>\n<div>\n 3.2 SECONDARY OBJECTIVES</div>\n<div>\n 1. Impact of VRC01 on viral dynamics in plasma over the course of 24 weeks.</div>\n<div>\n 2. Impact of VRC01 on HIV reservoir measures in peripheral blood mononuclear cells and</div>\n<div>\n plasma</div>\n<div>\n 3. Impact of VRC01 on clinical outcomes/characteristics of AHI</div>\n<div>\n 4. Impact of VRC01 on CD4 + T cell count</div>\n<div>\n 5. Pharmacokinetics of VRC01 in AHI in peripheral blood</div>\n<div>\n 3.3 EXPLORATORY OBJECTIVES</div>\n<div>\n 1. Impact of VRC01 on reservoir measures in CSF, mucosal, and tissue compartments</div>\n<div>\n 2. Comparison of peripheral blood reservoir measures to those in the CSF, mucosal and</div>\n<div>\n tissue compartments</div>\n<div>\n 3. Impact of VRC01 on reservoir measures in T cell subsets</div>\n<div>\n 4. Pharmacokinetics of VRC01 in CSF and mucosal compartments</div>\n<div>\n 5. Anti-VRC01 antibody detection</div>\n<div>\n 6. Impact of VRC01 on immune responses and activation</div>\n<div>\n 7. Effect of VRC01 on viral sequence, phenotype, and evolution</div>\n<div>\n 8. Predictors of favorable viral dynamics, immune responses, and reservoir seeding</div>\n<div>\n 9. Impact of VRC01 on neuropsychological testing outcomes</div>\n
      • principal_inclusion_criteria<p>\n 1. Able and willing to complete the informed consent process.<br />\n 2. Passes Test of Understanding<br />\n 0 20 40 60 80 100<br />\n 0<br />\n 2<br />\n 4<br />\n 6<br />\n 8<br />\n 10<br />\n Days From First RNA Positive<br />\n VL (log10 cps/ml)<br />\n days to Nadir<br />\n day to EIA<br />\n days to peak<br />\n 42<br />\n 15<br />\n 13<br />\n 4.2<br />\n 6.7<br />\n RV 398/WRAIR 2166 Version 2.0<br />\n 29 April 2015<br />\n Page 26 of 79<br />\n 3. 18 to 50 years of age.<br />\n 4. Experiencing early acute HIV-1 infection as defined by blood samples on at least two<br />\n separate days positive by nucleic acid testing within 21 days of a negative nucleic acid<br />\n HIV-1 test.<br />\n 5. No history of antiretroviral therapy for any indication<br />\n 6. In general good health<br />\n 7. Willing to have blood samples collected and stored.<br />\n 8. Able to participate for 25 weeks for study visits<br />\n 9. Willing to have photo or fingerprint taken for identification purposes<br />\n Female-specific Criteria:<br />\n 10. Agrees not to become pregnant from the time of study enrollment until the last study<br />\n visit. If a woman has no history of hysterectomy, tubal ligation or menopause, she must<br />\n agree to use an effective birth control method: abstinence; male or female condoms;<br />\n diaphragm or cervical cap with spermicide; intrauterine device; contraceptive hormones<br />\n delivered by pills, patch, injections, or vaginally; and hormonal implants under the skin;<br />\n or a male partner who has previously undergone a vasectomy.<br />\n 11. Negative β-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day<br />\n of enrollment for any woman unless she is post-menopause for 24 consecutive months or<br />\n has undergone a surgical procedure that precludes pregnancy.</p>\n
      • principal_exclusion_criteria<p>\n Exclusion Criteria<br />\n 1. Weight < 46 kg or >115kg<br />\n 2. Previous receipt of humanized or human monoclonal antibody whether licensed or<br />\n investigational.<br />\n 3. Ongoing AIDS-related opportunistic infection (including oral thrush or active<br />\n tuberculosis).<br />\n 4. Severe acute retroviral syndrome (as defined in Appendix 1) or other clinical condition<br />\n constituting an indication for immediate antiretroviral therapy per local country<br />\n guidelines.<br />\n 5. Active injection drug use within previous 12 months.<br />\n 6. History of a severe allergic reaction with generalized urticaria, angioedema or<br />\n anaphylaxis in the 2 years prior to enrollment.<br />\n 7. History of chronic urticaria<br />\n 8. Physical finding on examination considered indicative of significant disease such as<br />\n murmur (other than functional), hepatosplenomegaly, focal neurological deficit.<br />\n 9. Hypertension that is not well controlled by medication.<br />\n 10. Positive Hepatitis B surface antigen at any time in the past<br />\n RV 398/WRAIR 2166 Version 2.0<br />\n 29 April 2015<br />\n Page 27 of 79<br />\n 11. History of hepatitis C infection<br />\n 12. Untreated syphilis infection<br />\n 13. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2x the upper<br />\n limit of normal (ULN).<br />\n 14. Absolute neutrophil count (ANC) <740 cells/mm3<br />\n 15. Estimated GFR < 50 ml/min within the past 90 days<br />\n 16. Breast-feeding.<br />\n 17. Pregnancy<br />\n 18. Receipt of licensed vaccine or other investigational study agent within 28 days prior to<br />\n enrollment or past participation in an investigational HIV vaccine study with receipt of<br />\n active product.<br />\n 19. Current or planned participation in another interventional clinical trial during the study<br />\n period.<br />\n 20. Chronic or recurrent use of medications that modify host immune response, e.g., oral or<br />\n parenteral steroids, cancer chemotherapy.<br />\n 21. Any other chronic or clinically significant medical condition that in the opinion of<br />\n investigator would jeopardize the safety or rights of the volunteer. Including, but not<br />\n limited to: diabetes mellitus type I, chronic hepatitis, renal failure; OR clinically<br />\n significant forms of: drug or alcohol abuse, mental illness, severe asthma, autoimmune<br />\n disease, psychiatric disorders, heart disease, or cancer.<br />\n 22. Study site employee</p>\n
      • primary_end_points<p>\n 1. Safety: mAb related - grade 3 or greater reactogenicity and product related AEs<br />\n <br />\n 2. Log change in plasma viral load from day 0 to day 7</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans1
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Site Principal Investigator<br />\n Josphat Kosgei,<br />\n MBChB, MSc<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone: 254-729-110122, E-mail: josphat.kosgei@usamru-­â€k.org<br />\n Study Coordinator<br />\n Elizabeth Ngetich,<br />\n BSN<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n E-mail: elizabeth.ngetich@usamru-­â€k.org<br />\n Associate Investigators<br />\n Fredrick Sawe,<br />\n MBChB, MMed.<br />\n Senior Deputy Director,<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone: 254-724-255-623, E-mail: fredrick.sawe@usamru-­â€k.org<br />\n Samuel Sinei,<br />\n MBChB, MMed<br />\n Program Director<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone: 254-727-531-396, E-mail: samuel.sinei@usamru-­â€k.org<br />\n Deborah Chepng’eno<br />\n Langat, MBChB,<br />\n MSc<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n E-mail: Deborah.langat@usamru-­â€k.org<br />\n RV 398b/WRAIR 2166b Page 2 of 4 Version 2.0<br />\n Protocol Team Roster 08 June 2015<br />\n Lucy C. Koech,<br />\n MBChB<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Pharmacy Head, &Hospital Road, P.O. Box 1357, Kericho, 20200;<br />\n Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone: 254-726-290103, E-mail: lucy.koech@usamru-­â€k.org<br />\n Faith Riziki, B.<br />\n Pharm, MSc<br />\n Pharmacist of Record<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Pharmacy Head, &Hospital Road, P.O. Box 1357, Kericho, 20200;<br />\n Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone: 254-726-290103, E-mail: Faith.Riziki@usamru-­â€k.org<br />\n Joseph Oundo, MSc,<br />\n PhD<br />\n Laboratory Director,<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Clinical Research Center Laboratory.<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n E-mail: joseph.oundo@usamru-­â€k.org<br />\n Ignatius Kiptoo, BSc,<br />\n MSc<br />\n Information Technology Department Head.<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone:254-727-531375; E-mail: ignatius.kiptoo@usamru-­â€k.org<br />\n DoD Research Monitors<br />\n Jonah Maswai,<br />\n MBChB, MPH<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone:254-716-430271; E-mail: jonah.maswai@usamru-­â€k.org<br />\n Appolonia Aoko,<br />\n MBChB, MPH<br />\n Kenya Medical Research Institute/Walter Reed Project HIV Program<br />\n Hospital Road, P.O. Box 1357, Kericho, 20200; Kenya<br />\n Office: (254-52) 30686, 30388, Fax: (254-52) 30546<br />\n Mobile phone:254-715-551234; E-mail: appolonia.aoko@usamru-­â€k.org</p>\n
      • other_details_explanation<p>\n The source cohort study for this study is not being carried out in the USA, hence only the countries with the source cohort are participating. Two protocols (VRC 601 and VRC 602) utiling the same experimental product as this study are being carried out in the USA.</p>\n
      • other_details_regulatory_notapproved<p>\n None.</p>\n
      • other_details_regulatory_approved<p>\n KEMRI. One site in Kenya. Approval date - 21 september 2015.</p>\n
      • other_details_regulatory_rejected<p>\n None.</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable.</p>\n
      • estimated_duration25 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, 0.9% Saline
      • design_controlled_other_medicinalYes
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI Walter Reed Project Kericho
      • single_site_physical_addressHospital Road
      • single_site_contact_personDr Josphat Kosgei
      • single_site_telephone+254 729 110 122
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites
      • multi_country_listKenya, Uganda, Tanzania, Thailand
      • data_monitoring_committeeYes
      • total_enrolment_per_site6
      • total_participants_worldwide24
      • 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_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyNo
      • 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_nameElizabeth
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      • final_report<div>\n <strong>To:</strong> The Registrar,</div>\n<div>\n Pharmacy and Poisons Board,</div>\n<div>\n P.O. Box 27663- 00506</div>\n<div>\n NAIROBI. KENYA.</div>\n<div>\n  </div>\n<div>\n <strong>Attn: Expert Committee on Clinical Trials</strong></div>\n<div>\n  </div>\n<div>\n From: Josphat Kosgei, MBChB; MSc, DLSHTM</div>\n<div>\n Principal Investigator PPB/ECCT/15/10/01</div>\n<div>\n KEMRI/WRP HIV Program</div>\n<div>\n P.O Box 1357- 20200 Kericho, Kenya</div>\n<div>\n Tel; 052 5220 36100</div>\n<div>\n Email: Josphat.Kosgei@usamru-k.org</div>\n<div>\n  </div>\n<div>\n <strong>SUBJECT</strong>: Submission of the Study's Close Out Executive Summary Report for ECCT/15/10/01 protocol titled: “Safety and Virologic Effect Of A Human Monoclonal Antibody, VRC-HIVmAb060-00-Ab (VRCOl), With Broad HIV-1 Neutralizing Activity, Administered Intravenously to Adults During Early Acute HIV Infection.’’(RV 398b).</div>\n<div>\n  </div>\n<div>\n The purpose of this memo is to submit the close out executive summary report for the above-mentioned study for PPB/ECCT notification and acknowledgement.</div>\n<div>\n  </div>\n<div>\n <strong>1. INTRODUCTION:</strong></div>\n<div>\n This was a placebo-controlled study of the safety and impact of broadly neutralizing monoclonal antibody (mAb) therapy with VRC01 on viral dynamics in acute HIV infection, alone or in combination with antiretroviral therapy (ART). Subjects were enrolled during early acute HIV infection (AHI): defined as two positive nucleic acid amplification tests (NAATs) for HIV-1 RNA within 21 days of a prior negative NAAT. They were randomized to one of three groups:</div>\n<div>\n • Group 1, Immediate ART and placebo infusion (n=8): start ART with a single infusion of placebo on day 0 during AHI .</div>\n<div>\n • Group 2, Immediate ART and mAb Therapy (n=8): start ART with a single infusion of 40 milligrams/kilograms (mg/kg) VRC01 on day 0 during AHI</div>\n<div>\n • Group 3, Immediate mAb Therapy and Subsequent ART (n=8): a single infusion of 40 mg/kg VRC01 on day 0 during AHI followed by ART initiation on day 7</div>\n<div>\n  </div>\n<div>\n <strong>2. RESEARCH OBJECTIVES:</strong></div>\n<div>\n a) <strong>Primary Objective</strong></div>\n<div>\n 1. Safety of VRC01 in acutely HIV-infected individuals.</div>\n<div>\n 2. Impact of VRC01 on plasma viremia in each mAb arm compared to the ART plus placebo control at day 7 (+/- 1 day).</div>\n<div>\n 3. <strong>SUMMARY OF STUDY RESULTS:</strong></div>\n<div>\n For groups 1 and 2, participants and study team were blinded to active mAb vs. placebo infusion. After day 7, all groups were on ART and followed for 24 weeks.</div>\n<div>\n US Army Medical Research Directorate-Africa</div>\n<div>\n From 11 December 2016 to 31 May 2018, fifteen subjects were enrolled in RV398 at 3 sites in East Africa and 1 site in Thailand. All fifteen have completed their follow-up. RV217, the source protocol for recruiting acutely HIV-infected participants into RV398, was closed on 30 September 2018. No further study activities have since occurred at the East African sites. From 01 June 2018 to 12 February 2020, there were no enrollments into RV398 as the protocol was modified to recruit acutely HIV-infected participants enrolling in RV254 and to add a new study site, South East Asia Research Collaboration in HIV (SEARCH) Clinic, Thai Red Cross AIDS Research Center (TRCARC), Bangkok, Thailand. Since 13 February 2020 when enrollment began at SEARCH, nine participants have been enrolled into RV398.</div>\n<div>\n The study has now enrolled 24 of the 24 subjects permitted by the protocol. With the onset of the COVID-19 outbreak, the SEARCH team adopted enhanced infection prevention and control measures to mitigate risk and allow for continued low volume enrollment in the RV254 source cohort and in RV398 while pausing optional invasive procedures for study participants.</div>\n<div>\n In Kenya Kericho, the site was originally approved to enroll 6 participants. 6 participants were enrolled, and all participants completed all study activities.</div>\n<div>\n Infusions have been well tolerated. A summary of the data and adverse events for the overall study was just reviewed by the Safety Monitoring Committee (SMC) in the 13 January 2021 SMC Report (Attached).</div>\n<div>\n The cumulative deviation log, which includes all major and minor deviations that occurred in the study, is attached herein and the same have been uploaded on the ECCT portal.</div>\n<div>\n 4. List publications arising from study (attach copies of the manuscript(s).</div>\n<div>\n A summary of the data and adverse events for the overall study was reviewed by the Safety Monitoring Committee (SMC) in the 13 January 2021 and 13 July 2020 SMC Reports Attached herein.</div>\n<div>\n 5. Confirm destruction of each study participant’s identifiers and provide an assurance/evidence that the destruction has occurred (send copies of the blacked-out books).</div>\n<div>\n Data obtained from the conduct of this study are housed in a secure database maintained by the DCAC, MHRP, WRAIR. DCAC serves as the central data management facility for MHRP research protocols. Data managed by DCAC are entered into and maintained in a password-protected database accessible only to participating sites, DCAC and Information Technology staff authorized to work on the protocol. The database is located at the Bethesda campus of MHRP and is protected by a firewall. This data does not contain participant names or national identification number, but is referenced only by the study identification number. The clinical database is currently locked, and DCAC will maintain it indefinitely or until there is a regulatory requirement or sponsor instructions to destroy it. At the Kericho site the PI maintained research records of participants’ participation for this study. All participants received study numbers that were known only to the investigators and clinic staff. Clinical tests were identified by the study number and the specimen bag was identified by the study number and bar code only. The subject ID does not contain any identifiable information or any information which can be used to identify a study participant either directly or indirectly. These identification numbers were used for medical records, all laboratory tests or samples stored for testing in future studies. The study participants’ medical records were stored at the Clinical Research Center (CRC) archive room which is access controlled and double locked. The study documents have now been transferred to a safe, secured, long-term archive room within the Kericho CRC that is only accessible to regulatory personnel. All other research staff do not have access to this archive room. Destruction approval will be obtained from the sponsor and the IRBs will be notified when this is done. Any publication of this study will not use the study participant’s name or identify him/her personally. Efforts will be made to keep the study participants’ personal information confidential. The personal information may be disclosed if required by law. Clinical and research records may be reviewed by the representative of the KEMRI SERU, DAIDS, USAMRMC, WRAIR, representatives of the USAMRMC ORP,</div>\n<div>\n US Army Medical Research Directorate-Africa</div>\n<div>\n representatives of the FDA, OHRP, the product and device providers, and other regulatory agencies as part of their responsibilities for insuring the protection of research participants. Every effort will be made to keep the records as confidential as possible within the limits of the law. All data and medical information obtained about participants, as individuals will be considered privileged and held in confidence. Identification photographs did not contain participants’ names, but only a four-digit Study Number. A file copy of the photograph was kept in a secure location with other study documents and was only accessible to study staff. Research and clinical information relating to participants was shared with other investigators and the scientific community through presentation or publication; however, participants were NOT identified by name or social security number. Electronic data will be stored at least as long as the IND remains open. All participants received an emergency card indicating their status as a clinical trial participant. All participants were counseled periodically regarding the potential for testing positive on routine screening tests for HIV-1 as a consequence of participation in this trial and receiving this vaccine product. All participants were offered further confirmatory testing and certification as to the nature of their vaccine trial participation whenever needed to address complications arising at home, at work, or in the community, which could arise from routine screening for HIV.</div>\n<div>\n 6. Destruction of each study participant’s identifiers and provide an assurance/evidence that the destruction has occurred (send copies of the blacked-out books).</div>\n<div>\n Study documents have been transferred to a safe, secured, long-term archive room that is only accessible to two regulatory personnel. All other research staff does not have access to this archive room. Access to study documents is controlled and restricted and the site is responsible for ensuring that any access is accurately recorded and any documents accessed/removed and returned are recorded. Destruction approval will be obtained from the sponsor and the IRBs will be notified when this is done.</div>\n<div>\n 7. Plan for future use of data from the study (if applicable)</div>\n<div>\n All work for this study is complete. There are no future plans and any future use of individually coded data will have to be approved by the IRB. No further use of specimens or data can occur until a new protocol is approved and authorized by the WRAIR Institutional Review Board (IRB) and KEMRI SERU.</div>\n<div>\n 8. Confirm destruction of surplus investigational agents and provide an assurance/evidence that the destruction has occurred (if applicable).</div>\n<div>\n Attached is RV 398 Investigation Products Destruction Authorization Documents.</div>\n<div>\n 9. Detail the plan for the destruction, storage, or future use of biological specimens obtained as part of this study (include number of samples being destroyed or stored).</div>\n<div>\n All the samples that were not for safety testing were shipped out with the approval Scientific and Ethics Review Unit for analysis. The site is not storing any study samples</div>\n<div>\n  </div>\n<div>\n <strong>Find below the summary.</strong></div>\n<div>\n US Army Medical Research Directorate-Africa</div>\n<div>\n RV 398 -Sample Shipment</div>\n<div>\n Aliquot type</div>\n<div>\n Quantity</div>\n<div>\n Lymph Node fixed</div>\n<div>\n 11</div>\n<div>\n Rectal BX Fixed</div>\n<div>\n 6</div>\n<div>\n CSF Large Cells</div>\n<div>\n 15</div>\n<div>\n CSF Small Cells</div>\n<div>\n 48</div>\n<div>\n CSF Supernatant</div>\n<div>\n 246</div>\n<div>\n PBMC</div>\n<div>\n 294</div>\n<div>\n Plasma</div>\n<div>\n 387</div>\n<div>\n Recatal Bx VRC01 Lv1</div>\n<div>\n 2</div>\n<div>\n REctal Bx RNA Later</div>\n<div>\n 32</div>\n<div>\n Rectal Bx VRC01 Lv1</div>\n<div>\n 4</div>\n<div>\n Rectal Sponge</div>\n<div>\n 19</div>\n<div>\n Serum</div>\n<div>\n 151</div>\n<div>\n Soft Cup</div>\n<div>\n 61</div>\n<div>\n TOTAL</div>\n<div>\n 1276</div>\n<div>\n  </div>\n<div>\n Thank you for your time and review.</div>\n<div>\n  </div>\n<div>\n <strong>Included in this submission are the following:</strong></div>\n<div>\n a) Initial ECCT approval letter dated 08 January 2016.</div>\n<div>\n b) ECCT annual approval letter dated 22 January 2021.</div>\n<div>\n c) Safety Monitoring Committee (SMC) Report Dated 13 January 2021.</div>\n<div>\n d) Safety Monitoring Committee (SMC) Report Dated 13 July 2021.</div>\n<div>\n e) WRAIR# 2166B Closeout Acceptance Memo Dec 2020.</div>\n<div>\n f) KEMRI SERU#3096 Closeout Acceptance Memo dated 03 May 2021.</div>\n<div>\n g) Cumulative Deviation Log.</div>\n<div>\n h) RV 398 Investigation Products Destruction Authorization Documents.</div>\n<div>\n  </div>\n<div>\n The point of contact for this action is <strong>Dr. Josphat Kosgei</strong> at the Kenya Medical Research Institute-US Army Medical Research Directorate-Africa, who can be reached by email at <strong>josphat.kosgei@usamru-k .org.</strong></div>\n<div>\n  </div>\n<div>\n  </div>\n
      • implication_results<p>\n  </p>\n<p>\n <span style=\"font-size:14px;\">Yes,VRC01 intervention during early acute HIV infection was seen to be well tolerated and thus to ensure and determine whether it could significantly play a vital role in viral suppression, it may be imperative to encourage further development of it together with other immunotherapies for HIV directed against unique therapeutic targets.</span></p>\n
      • quantity_imported1. VRC-HIVmAb060-00-Ab (VRCOl) = 80 (2) 0.9%Sodium Chloride Inj USP 50ml = 24
      • quantity_dispensed1. VRC-HIVmAb060-00-Ab (VRCOl) = 45 (2) 0.9%Sodium Chloride Inj USP 50ml = 2
      • quantity_destroyed1. VRC-HIVmAb060-00-Ab (VRCOl) = 35 (2) 0.9%Sodium Chloride Inj USP 50ml = 22
      • quantity_exported1. VRC-HIVmAb060-00-Ab (VRCOl) = 0 (2) 0.9%Sodium Chloride Inj USP 50ml = 0
      • balance_site1. VRC-HIVmAb060-00-Ab (VRCOl) = 0 (2) 0.9%Sodium Chloride Inj USP 50ml = 0
      • final_date0000-00-00
      • modified2024-12-17 15:41:52
      • created2015-10-07 16:37:05
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