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    • Application(array)
      • id1398
      • user_id81
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      • abstract_of_study<p>\n The Severe Malaria Africa – A Consortium for Research and Trials (SMAART) aims to significantly improve outcomes for severe malaria through enhanced and accelerated research initiatives. SMAART serves as an efficient operational platform for coordinating future research, enabling continuous updates to disease definitions and treatment guidelines based on the latest evidence. During its 2-day inception meeting, SMAART assembled a multidisciplinary team including scientists from major Wellcome Trust programs (KEMRI in Kenya, Malawi-Liverpool-Wellcome Trust Unit in Malawi, Mahidol Oxford Tropical Medicine Research Unit in Thailand), clinical trial experts (MRC CTU at UCL), and African clinician scientists from multiple countries.</p>\n<p>\n The meeting focused on establishing the current burden of severe malaria through literature review, updating our understanding of the disease's clinical spectrum, identifying accurate diagnostic tools, and setting best practices to address research gaps. Key discussions revolved around refining practice guidelines in response to challenges like artemisinin resistance and persistently high mortality rates despite effective antimalarial treatments. The meeting also laid out plans for future clinical trials, emphasizing pathophysiological research and innovative trial methodologies.</p>\n<p>\n Despite various supportive therapies being explored through ongoing and planned clinical trials, the evidence remains sparse, underlining the urgent need for more comprehensive studies. The consortium stressed the necessity of an adaptive trial platform to properly evaluate potential beneficial adjunctive therapies and identified high-priority risk factors and interventions for a Phase II platform trial aimed at improving short and long-term outcomes.</p>\n<p>\n This structured approach aims to address severe malaria with targeted treatments and innovative research methodologies, with each intervention's background, justification, and rationale detailed in specific appendix protocols.</p>\n
      • study_title<div>\n Severe Malaria A Research and Trials consortium - Multisite Adaptive Platform trial</div>\n
      • laymans_summary<div>\n Children with severe malaria come to hospital very sick and need urgent care. Despite the introduction of the malaria vaccine in some areas of Africa and increased bednet use, severe malaria is still causing child deaths and hospitalisations. Even on the best anti-malarial treatments many African children with severe malaria have poor outcomes with including deaths which tend to occur on the first day of arrival to hospital. One of the bad things that happen in severe malaria is that red blood cells that are infected with malaria parasites stick to the very deep parts of our blood vessels. This occurs throughout the body and affects vital places such as the brain or kidneys. Thus, children come to hospital with different symptoms such as in a coma or with fits or with anaemia. They will be treated immediately with anti-malarials and may also receive antibiotics. Other treatments targeted at symptoms or specific areas of the body may also help them recover (called adjunctive therapy).</div>\n<div>\n The World Health Organisation has developed guidelines for treatment of severe malaria but much of the information used to develop the recommendations on adjunctive therapy are based on expert opinion and not data from clinical trials and studies which are a better source of evidence. The SMAART-MAP trial aims to identify adjunctive therapies that will help children with severe malaria get better faster in the short term (within 3 days of coming to hospital) and that could then be studied further in larger numbers to see if they are able to reduce the number of children who die or return to hospital.</div>\n<div>\n The trial has been designed to look at the impact of these adjunctive therapies on different symptoms or body areas. In the trial these different areas are called ‘domains’. One adjunctive therapy will be investigated within each domain of the trial. It is called an adaptive trial as new domains can be added to the structure of the trial after it has started, and all domains have some joint processes and will be run by the same staff. This document is the master protocol which outlines those joint processes and explains the main objective of the trial. Appendices describe the adjunctive therapies within each domain in more detail.</div>\n<div>\n A computer programme will assign a child to receive either the adjunctive treatment or the standard of care at that site within a domain at random (like the flip of a coin). Each child can only be enrolled to one domain and thus possibly receive one adjunctive treatment through the trial. Each child will be monitored through bedside observations and depending on the domain they may need some additional tests. This information will help us compare how children receiving the adjunctive therapy and receiving standard of care are responding to their treatment.</div>\n
      • short_titleSMAART-MAP trial
      • protocol_noECCT/24/04/03
      • version_no1.02
      • date_of_protocol09-02-2024
      • study_drugSMAART_MAP Trial_(Levetiracetam,Paracetamol and Blood products\' (whole blood and Package Cells)
      • disease_conditionSevere Malaria
      • product_type_biologicals1
      • product_type_proteins1
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
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      • product_type_medical_device0
      • product_type_chemical_nameParacetamol and Levetiracetam
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressCGMRCCSC@kemri-wellcome.org
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      • declaration_applicantEmmanuel Oguda
      • declaration_date107-08-2024
      • declaration_principal_investigatorProf.Kathryn Maitland
      • declaration_date207-08-2024
      • placebo_presentNo
      • study_objectives<p>\n The SMAART-MAP trial aims to identify promising adjunctive therapies for advancement into a comprehensive Phase III trial focused on severe malaria with an emphasis on mortality outcomes. Utilizing an adaptive platform design, the trial is structured to incorporate multiple domains, enabling the evaluation of various adjunctive therapies across diverse clinical manifestations of severe malaria efficiently.</p>\n<p>\n <strong>Primary Objective</strong></p>\n<ul>\n <li>\n The primary objective is to evaluate the therapeutic efficacy of each intervention within its respective domain. This evaluation will utilize early indicators such as biomarkers or clinical assessments conducted within 24-72 hours post-intervention.</li>\n</ul>\n<p>\n <strong>Secondary Objectives</strong></p>\n<ul>\n <li>\n To determine the impact of the interventions on clinical outcomes, including readmission rates and mortality, assessed at 28 days and 90 days following randomization.</li>\n <li>\n To evaluate the incidence and severity of Grade 3 or 4 adverse events, as well as any adverse events associated with the interventions or their comparators.</li>\n <li>\n To explore the effects of defined severe malaria criteria, specifically platelet counts ≤150,000/μL and plasma pfHRP2 concentrations ≥800 ng/mL, on the differentiation between randomized groups.</li>\n <li>\n In a sub study, to assess the performance characteristics of a point-of-care (POC) pfHRP2 test in comparison with quantitative plasma pfHRP2 measurements.</li>\n</ul>\n<p>\n These objectives are designed to guide the systematic exploration and evaluation of adjunctive therapies in the treatment of severe malaria, thereby contributing to improved treatment strategies and outcomes.</p>\n
      • principal_inclusion_criteria<p>\n Eligibility criteria for SMAART-MAP (all domains)</p>\n<ol>\n <li>\n Aged >3 months and <12 years</li>\n <li>\n Admitted to the paediatric ward in the last 24 hours at screening</li>\n <li>\n Current or recent evidence of malaria (slide or rapid diagnostic test (RDT) positive in this admission)</li>\n <li>\n Guardian willing to provide consent</li>\n</ol>\n<div>\n <strong>Additional domain-specific inclusion criteria.</strong></div>\n<div>\n <div>\n Severe Anaemia Domain</div>\n <ol>\n <li>\n Hb <6g/dl</li>\n <li>\n One or more or the following severity signs: Hb<4g/dl, prostration, impaired consciousness, respiratory distress, history of passing red or coca-coloured urine in this illness</li>\n </ol>\n</div>\n<p>\n Cerebral Malaria Domain (EITHER)</p>\n<ol>\n <li>\n One or more reported seizures in the current episode of illness and altered consciousness (BCS≤4) at screening OR</li>\n <li>\n Presence of coma (BCS ≤2) at screening regardless of history.</li>\n</ol>\n<p>\n Renal function Domain</p>\n<ol>\n <li>\n Creatinine >1.5xULN on point-of-care assay or laboratory test at screening</li>\n <li>\n Meet one of the current WHO severity criteria (clinical or laboratory (where these tests are done routinely)) (Group 1 and 2 from the recent WHO reclassification of severe malaria)</li>\n</ol>\n
      • principal_exclusion_criteria<p>\n Domains specific exclusion criteria.</p>\n<p>\n <strong>Severe Anaemia Domain</strong></p>\n<ol>\n <li>\n Known congenital or valvular heart disease (not surgically corrected)</li>\n</ol>\n<p>\n <strong>Cerebral Malaria Domain</strong></p>\n<ol>\n <li>\n Received an anticonvulsant within 6 hours of screening or between screening and randomisation.</li>\n <li>\n Known cerebral palsy or significant neuro-development delay.</li>\n</ol>\n<p>\n <strong>Renal function Domain</strong></p>\n<ol>\n <li>\n Received paracetamol within 6 hours of screening or between screening and randomisation</li>\n <li>\n Known allergy to paracetamol</li>\n <li>\n Severe malnutrition (middle upper arm circumference MUAC<11.5cm)</li>\n</ol>\n
      • primary_end_points<p>\n Primary endpoints are specific to each domain which include.</p>\n<p>\n Cerebral Malaria Domain</p>\n<ul>\n <li>\n Number of witnessed seizures sufficient to start or change anticonvulsant medication by 72 hours.</li>\n</ul>\n<p>\n Renal Function Domain</p>\n<ul>\n <li>\n Area Under the Curve (AUC) for creatinine over the first 72 hours from randomization based on measurements assayed retrospectively on stored plasma samples taken at randomisation (treated as time 0/baseline) at 24, 48, and 72 hours.</li>\n</ul>\n<p>\n Severe Anaemia Domain:</p>\n<ul>\n <li>\n Change in haemoglobin at 24 hours (adjusted for baseline)</li>\n</ul>\n<p>\n <strong>Secondary endpoints</strong></p>\n<p>\n These will encompass all domains and will include.</p>\n<ul>\n <li>\n Readmissions and mortality to day 28 and day 90.</li>\n <li>\n Grade 3 or 4 adverse events (AEs); and AEs judged related to domain-specific interventions or their comparators during admission as detailed in the domain-specific appendices.</li>\n</ul>\n
      • scope_diagnosis0
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      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
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      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n <strong>Kilifi_Kenya</strong></div>\n<div>\n  </div>\n<div>\n We will draw study clinicians and nurses from the staff currently working in the KEMRI HDU Research Unit, and they will be trained on all aspects of the study protocol and procedures. Additionally, a dedicated study clinician and nurse will closely assist in the operation of the study activities within the trial unit (HDU).</div>\n<p>\n Trial Coordinator: Emmanuel Oguda</p>\n<p>\n The trial will be coordinated and conducted in the KEMRI High Dependency Unit, as well as in other designated pediatric units across various participating sites located in seven hospitals in Africa.</p>\n<p>\n Chief Principal Investigator: Professor Kathryn Maitland will oversee the trial overall.</p>\n<p>\n Local Principal Investigator: Professor Mainga Hamaluba will be responsible for local oversight.</p>\n<p>\n Each site will be overseen and evaluated by specific Country Principal Investigators (PIs) as listed below:</p>\n<p>\n <strong>Democratic Republic of the Congo</strong></p>\n<p>\n Université de Kinshasa, Campus UNIKIN, Lemba, BP 11850, Kinshasa, DRC</p>\n<p>\n Principal Investigator: Prof Marie Onyamboko, MD, DPhil</p>\n<p>\n Co-Investigator: Dr. Catarina Fanello, PhD</p>\n<p>\n <strong>Uganda</strong></p>\n<p>\n Country Principal Investigator: Prof. Peter Olupot Olupot</p>\n<p>\n <strong>Soroti Regional Hospital</strong></p>\n<p>\n Co-Investigator: Dr. Florence Aloroker, MBChB, MMed</p>\n<p>\n Study Site Coordinator: Denis Amorut, BsHSM, RCN</p>\n<p>\n <strong>Dr. Ambrosoli Hospital, Kalongo</strong></p>\n<p>\n Site Investigator: Dr. Okao Maurice, MD, MMED Pediatrics</p>\n<p>\n Study Site Coordinator: Dr. Modester Akite, MD</p>\n<p>\n <strong>Zambia</strong></p>\n<p>\n St. Paul's Mission Hospital, Nchelenge, Luapula Province</p>\n<p>\n Tropical Diseases Research Centre, Ndola Teaching Hospital, P.O Box 71769, Ndola</p>\n<p>\n Principal Investigator: Dr. Mike Chaponda, MSc, MBChB, MSc, DTMH</p>\n<p>\n Co-Investigators: Dr. Sam Miti, MBChB, MMed; Dr. Jonathan Gwasupika, MBChB</p>\n<p>\n <strong>Ghana</strong></p>\n<p>\n Komfo Anokye Teaching Hospital, Bantama High Street, P.O Box 1934, Kumasi</p>\n<p>\n Department of Child Health, Kwame Nkrumah University of Science and Technology, Kumasi</p>\n<p>\n Principal Investigator: Professor Daniel Ansong, MBChB, MSc</p>\n<p>\n Co-Investigators: Prof. Tsiri Agbenyega, PhD; Dr. Justice Sylverken, MBChB</p>\n<p>\n <strong>Mozambique</strong></p>\n<p>\n Hospital Central de Quelimane, Av. Julius Nyerere, Estrada Regional Numero 470, Bairro Namuinho</p>\n<p>\n Manhiça Health Research Centre (CISM), P.O BOX 1929, Manhiça</p>\n<p>\n Co-Lead Investigators: Dr. Rosauro Varo, MD, MSc, PhD, Pediatrician; Dr. Pedro Aide, MD, MSc, PhD</p>\n<p>\n Co-Investigator: Dr. David Torres, MD, MSc, Pediatrician</p>\n<p>\n Co-Investigator: Professor Quique Bassat, MD, MSc, PhD</p>\n
      • other_details_explanation<p>\n The SMAART-MAP trial is being conducted in Kenya, among other African countries, to study hospitalized children with severe malaria, leveraging local hospitals to investigate potential treatments and interventions in a real-world setting where malaria prevalence is high. This facilitates direct evaluation of medical strategies in environments most affected by the disease, aiming to improve patient outcomes and inform future healthcare practices in similar regions.</p>\n
      • other_details_regulatory_notapproved<ol>\n <li>\n Zambia Medicine Regulatory Authority_(ZAMRA)_Zambia</li>\n <li>\n Food and Drugs Authority (FDA) _Ghana</li>\n <li>\n National Medicines Regulatory Authority (Autoridade Nacional Reguladora de Medicamentos, ANARME) _Mozambique</li>\n <li>\n Comité d'Ethique de la Recherche ECOLE DE SANTÉ PUBLIQUE DE KINSHASA</li>\n <li>\n UNIVERSITE DE KINSHASA_Democratic Republic of Congo</li>\n <li>\n National Drug Authority _NDA (Uganda)</li>\n</ol>\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_duration24 months
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorStandard of Care
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKilifi County Hospital
      • single_site_physical_addressP.o Box 230 Kilifi
      • single_site_contact_personEmmanuel Oguda
      • single_site_telephone0748588041
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states6
      • number_of_sites
      • multi_country_listUganda, Zambia, Ghana, Kenya, Democratic Republic of the Congo and Mozambique
      • data_monitoring_committeeYes
      • total_enrolment_per_siteThe minimum number of participants expected per site is 10, while the maximum is 60.
      • total_participants_worldwide450
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationYes
      • subjects_incapable_consentYes
      • subjects_specifySick children below the age of 12 years
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameProf Mainga Hamaluba
      • investigator1_middle_name
      • investigator1_family_nameHamaluba
      • investigator1_qualificationMedical Doctor
      • investigator1_professional_addressKilifi Clinical Trials Unit, PO Box 230, Kilifi
      • investigator1_telephone+254 709983946
      • investigator1_emailMHamaluba@kemri-wellcome.org
      • organisations_transferred_Yes
      • number_participantsSince this is a multi-centred trial, the enrollment of study participants will be competitive across the participating sites.
      • notification<p>\n We have uploaded all the relevent document sfor review as per the checklist for submission clinical trials application for approval. </p>\n<h1>\n  </h1>\n
      • approval_date29-08-2024
      • submitted1
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      • date_submitted15-04-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted15-04-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been reviewed under the AVAREF pathway and approved.
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      • modified2025-03-18 14:50:38
      • created2024-04-15 08:48:11
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      • ecitizen_invoice362299
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        • id1059
        • application_id1398
        • given_nameProf Kathryn Maitland
        • middle_name
        • family_nameMaitland
        • qualificationProfessor of Paediatric Tropical Infectious Diseases (MBBS PhD)
        • professional_addressBOX 230 KILIFI
        • telephone+254733411022
        • emailkathryn.maitland@gmail.com
        • created2024-04-15 09:41:34
        • modified2024-08-07 16:24:21
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        • created2024-04-15 09:41:34
        • modified2024-08-07 16:24:21
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        • id740
        • application_id1398
        • sponsorImperial College London
        • sponsor_typeOthers
        • contact_personJoint Research Compliance Office
        • addressImperial College London Room 215, Level 2, Medical School Building Norfolk Place London, W2 1PG
        • telephone_numberTel: 020 7594 1872
        • fax_number
        • cell_numberTel: 020 7594 1872
        • email_addressr.nicholson@imperial.ac.uk
        • created2024-04-15 09:41:34
        • modified2024-08-07 16:24:21
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      • abstract_of_study<div>\n According to the Joint United Nations Programme on HIV/AIDS and the World Health Organization, as of the end of 2018, over 37.9 million people [32.7 – 44 million], were estimated to be living with HIV/AIDS. It is estimated that in 2018 alone, 1.7 million [1.6 – 2.3 million] were newly infected with HIV and 770,000 [570,000-1.1 million] people died of AIDS-related illnesses.The use of antiretroviral agents by HIV-uninfected individuals before potential sexual exposure to HIV-infected partners, known as pre-exposure prophylaxis (PrEP), is a new effective preventive approach against HIV-1. However, an important challenge to the success of such strategy is that its efficacy is highly dependent on adherence to a daily oral drug regimen.Therefore, the search for novel preventive and therapeutic interventions with a longer duration of action is of high priority. A new generation of highly potent broadly neutralizing antibodies (bNAbs) may represent a novel</div>\n<div>\n strategy to combat HIV-1 infection. Monoclonal antibodies, which are made in the laboratory but based upon natural human antibodies with high potency, are considered to be promising candidates for safe, long-acting preventive agents. In the past decade, a number of antibodies have been developed that have broad neutralizing ability, that is to say they neutralize a large number of HIV-1 isolates from different clades and geographic regions. Combinations of these antibodies have even broader activity. It will be important to have broad coverage, to protect against the wide variety of HIV-1 variants that are found in Africa and globally. In this study, we propose to study two such broadly neutralizing antibodies (bNAbs), in combination. Novel, Potent bNAbs: Selection and Preclinical characterization.The advent of single-cell cloning techniques allowed the identification of potent bNAbs that target multiple epitopes on the HIV-1 envelope. Some of the new bNAbs demonstrate in vitro neutralizing activity against over 90% of HIV-1 pseudoviruses derived from diverse clades, even at low concentrations. Broadly neutralizing antibodies are potential alternatives to standard antiretroviral drugs as they are likely to be safe and well tolerated, and to persist at neutralizing levels for longer periods of time. Below the characteristics of two novel bNAbs are described. Both antibodies have been evaluated in clinical studies, either alone or in combination. 3BNC117 and 10-1074 have shown favorable safety profiles in both HIV-infected and HIV-uninfected participants. Single infusions of 3BNC117</div>\n<div>\n or 10-1074 led to decline in plasma viremia of approximately 1.5 log10 copies/mL in viremic individuals, Experience with 3BNC117.</div>\n<div>\n  </div>\n<div>\n Neutralizing Activity</div>\n<div>\n 3BNC117 and 10-1074 are two of the most potent broadly neutralizing antibodies available. 3BNC117 targets the CD4 binding site, while 10-1074 targets the V3 loop of HIV-1 gp 120. They were chosen for clinical development for their neutralizing breadth and potency, and their antiretroviral activity when tested in humanized mice (hu-mice) and non-human primate (NHP) models. The neutralizing activities of 3BNC117 and 10-1074 were evaluated in vitro against large pseudovirus panels including diverse clades. 3BNC117 showed neutralizing activity against 82.5% of 399 pseudoviruses tested, while 10-1074 neutralized 61.7% of 295 pseudoviruses tested. The combination of these two antibodies, which target two nonoverlapping epitopes on HIV-1 gp 120 provides higher breadth and potency than either antibody alone. In vitro, the combination showed neutralizing activity against 96% of 125 viruses from multiple clades, with average IC80 0.15 μg/mL [15]. The 3BNC117 and 10-1074 combination neutralizing titers against a panel of 200 clade C viruses were predicted using the Bliss-Hill model. Against this panel, the 3BNC117 plus 10-1074 combination covered 87% of viral strains with IC80 of 0.16 μg/mL.</div>\n
      • study_title<div>\n Safety and Pharmacokinetics of the Combination Broadly Neutralizing  Antibodies, 3BNC117-LS-J and 10-1074-LS-J, in Healthy American and</div>\n<div>\n African Adults (IAVI C100)</div>\n
      • laymans_summary<p style=\"margin-left:4.5pt;\">\n Anti-HIV neutralizing antibodies were first cloned from B cells of HIV-infected individuals. The antibodies selected for clinical testing showed the ability to neutralize (block infection of new cells) HIV strains of multiple clades at very low concentrations. These two antibodies are specific for two different regions of the HIV envelope protein, the outer layer of the virus. 3BNC117 binds to the CD4 binding site and 10-1074 to the V3 loop of HIV. The combination of both antibodies covers a larger number of viral strains than either antibody alone. When the antibodies were given to mice and non-human primates, the antibodies protected the animals from infection or lowered viral loads in infected animals.</p>\n<p style=\"margin-left:4.5pt;\">\n The antibodies that were originally found in two HIV-infected individuals were cloned and manufactured in the laboratory for clinical testing. In early clinical trials the antibodies have showed good safety profiles and half-lives of about 2 weeks. Both antibodies were able to lower viral loads in HIV-infected persons not taking antiretrovirals. The combination of antibodies was able to maintain undetectable viral loads during a period of ART interruption.</p>\n<p style=\"margin-left:4.5pt;\">\n 3BNC117 and 10-1074 were subsequently modified to improve their half-lives and also their stability as future drug products. The two changes made to improve half-life prolonged half-life of 3BNC117 from about 2 weeks to about 10 weeks, and of 10-1074 from about 3 weeks to about 13 weeks. These long-acting antibodies (3BNC117-LS and 10-1074-LS) are being testing in two clinical trials in the US. So far, the antibodies have shown very good safety profiles, similar to the original unmodified antibodies. The antibodies that will be used in this proposed study have additional modifications to improve the antibody chemical characteristics, but these modifications do interfere with the antibody activities.</p>\n<p>\n  </p>\n
      • short_titleIAVI C100
      • protocol_noECCT/20/11/02
      • version_no1.0
      • date_of_protocol26-11-2019
      • study_drugBroadly Neutralizing Antibodies (3BNC117-LS-J and 10-1074-LS-J) - IAVI C100
      • 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_namePlacebo
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressRwamba@csrtkenya.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantPeter Mogere
      • declaration_date110-11-2020
      • declaration_principal_investigatorDr. Nelly Mugo
      • declaration_date210-11-2020
      • placebo_presentYes
      • study_objectives<div>\n <strong>Primary:</strong></div>\n<div>\n 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.</div>\n<div>\n 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.</div>\n<div>\n 3. To identify a regimen of the two antibodies that, when given SC every 3 months, will maintain a serum trough level of >10 μg/mL for each antibody in >80% of the study population.</div>\n<div>\n  </div>\n<div>\n <div>\n <strong>Secondary:</strong></div>\n <div>\n 1. To evaluate the effect of participant characteristics, e.g., sex, body weight or body mass index (BMI), on pharmacokinetic parameters.</div>\n <div>\n 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.</div>\n <div>\n 3. To assess the incidence and titers of anti-drug antibodies (ADA) against each antibody.</div>\n <div>\n  </div>\n <div>\n <strong>Exploratory:</strong></div>\n <div>\n 1. To evaluate the effect of geographic region, immunoglobulin levels, and the subcutaneous site on injection (abdomen vs. arm) on pharmacokinetic parameters.</div>\n <div>\n 2. To characterize the bNAb neutralization potency in serum or plasma.</div>\n <div>\n 3. To investigate the effect of ADA on antibody concentration and neutralizing potency and the potential occurrence of ADA-related adverse events.</div>\n <div>\n 4. To characterize mucosal distribution of the bNAbs in a subset of participants enrolled in African sites.</div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<div>\n 1. Healthy male and female individuals, as assessed by a medical history, physical exam, and laboratory tests</div>\n<div>\n 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</div>\n<div>\n 3. Willing to undergo HIV testing, risk reduction counseling and receive HIV test results; committed to maintaining low-risk behavior for the trial duration</div>\n<div>\n 4. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study;</div>\n<div>\n 5. In the opinion of the Principal Investigator or designee and based on Assessment of Understanding results, has understood the information provided and potential</div>\n<div>\n impact and/or risks linked to IP administration and participation in the trial; written informed consent will be obtained from the participant before any study-related</div>\n<div>\n procedures are performed;</div>\n<div>\n 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</div>\n<div>\n method of contraception from enrollment until 9 months after the last administration, including a minimum of one of the following:</div>\n<div>\n ï‚· Condoms (male or female) with or without spermicide, Intrauterine device</div>\n<div>\n <div>\n ï‚· Contraceptive implant</div>\n <div>\n ï‚· Hormonal contraception</div>\n <div>\n ï‚· Successful vasectomy in the male partner (considered successful if a woman reports that a male partner has [1] documentation of azoospermia by microscopy (< 1 year ago), or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity post-vasectomy)</div>\n <div>\n ï‚· Not be of reproductive potential, such as having undergone hysterectomy, bilateral oophorectomy, or tubal ligation, postmenopausal (> 45 years of age with amenorrhea for at least 2 years, or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone [FSH] level > 40 IU/L); surgically sterile: no additional contraception required</div>\n <div>\n Note: More restrictive measures may be required by study sites.</div>\n <div>\n 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.</div>\n <div>\n 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.</div>\n <div>\n 9. Willing to forgo donations of blood, or any other tissues during the study following confirmation of study eligibility and, for those who test HIV-positive due to</div>\n <div>\n antibody-induced seropositivity, until the anti-HIV antibody titers become undetectable on HIV tests used in the community</div>\n</div>\n<p>\n  </p>\n
      • principal_exclusion_criteria<div>\n 1. Confirmed HIV infection;</div>\n<div>\n 2. Reported risk for HIV infection within 6 months prior to investigational product administration, as defined by:</div>\n<div>\n ï‚· Unprotected sexual intercourse with a known HIV-infected person, a partner known to be at high risk for HIV infection and/or a casual partner (i.e. no continuing established relationship)</div>\n<div>\n ï‚· Engaged in sex work</div>\n<div>\n ï‚· Frequent excessive daily alcohol use or frequent binge drinking or any other use of illicit drugs</div>\n<div>\n ï‚· History of newly-acquired syphilis, gonorrhea, non-gonococcal urethritis, HSV-2, chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B or hepatitis C;</div>\n<div>\n ï‚· Three or more sexual partners;</div>\n<div>\n 3. Any clinically relevant abnormality on history or examination, including history of immunodeficiency or autoimmune disease; use of systemic corticosteroids (the</div>\n<div>\n use of topical or inhaled steroids is permitted), immunosuppressive, anticancer, anti-tuberculosis or other medications considered significant by the investigator</div>\n<div>\n within the previous 6 months;</div>\n<div>\n  </div>\n<div>\n <div>\n The following exceptions are permitted and will not exclude study participation: </div>\n <div>\n use of corticosteroid nasal spray for rhinitis, topical corticosteroids for an acute uncomplicated dermatitis; or a short course (duration of 10 days or less, or a</div>\n <div>\n single injection) of corticosteroid for a non-chronic condition (based on investigator clinical judgment) at least 2 weeks prior to enrollment in this study;</div>\n <div>\n  </div>\n <div>\n 4. Any clinically significant acute or chronic medical condition that is considered progressive or in the opinion of the investigator makes the participant unsuitable</div>\n <div>\n for participation in the study;</div>\n <div>\n 5. Asthma that is not well controlled;</div>\n <div>\n 6. If female, pregnant or planning a pregnancy during the period of enrollment until</div>\n <div>\n 9 months after the final IP administration; or lactating;</div>\n <div>\n 7. Bleeding disorder diagnosed by a physician (e.g., factor deficiency, coagulopathy or platelet disorder that requires special precautions) (Note: A participant who</div>\n <div>\n states that he or she has easy bruising or bleeding, but does not have a formal diagnosis and has IM injections and blood draws without any adverse experience, is eligible);</div>\n <div>\n 8. History of splenectomy;</div>\n <div>\n 9. Any of the following abnormal laboratory parameters listed below:</div>\n <div>\n  </div>\n <div>\n <strong>Hematology</strong></div>\n <div>\n ï‚· Hemoglobin – Africa participants: <9.5 g/dl in females; <11.0 g/dl in males</div>\n <div>\n ï‚· Hemoglobin – US participants: <10.5 g/dl in females; <11.0 g/dl in males</div>\n <div>\n ï‚· Absolute Neutrophil Count (ANC) – all participants: ≤1,000/mm3</div>\n <div>\n ï‚· Absolute Lymphocyte Count (ALC) – all participants: ≤650/mm3</div>\n <div>\n ï‚· Platelets – African participants: <100,000 cells/mm3</div>\n <div>\n ï‚· Platelets – US participants: <125,000 cells/mm3</div>\n <div>\n  </div>\n <div>\n <div>\n <strong>Chemistry</strong></div>\n <div>\n ï‚· Creatinine >1.1 x ULN and eGFR <60 mL/min/1.73m2</div>\n <div>\n ï‚· AST >1.25 x ULN</div>\n <div>\n ï‚· ALT >1.25 x ULN</div>\n <div>\n  </div>\n <div>\n <strong>Urinalysis</strong></div>\n <div>\n Clinically significant abnormal dipstick confirmed by microscopy:</div>\n <div>\n ï‚· Protein = 2+ or more</div>\n <div>\n ï‚· Blood = 2+ or more (not due to menses)</div>\n <div>\n  </div>\n <div>\n 10. Infectious disease diagnosis:</div>\n <div>\n  </div>\n <div>\n <div>\n 11. Receipt of blood transfusion or blood-derived products within the previous 3 months;</div>\n <div>\n 12. Participation in another clinical trial of an investigational product currently, within the previous 3 months or expected participation during this study (concurrent</div>\n <div>\n participation in an observational trial not requiring blood or tissue sample collection is not an exclusion);</div>\n <div>\n 13. Prior receipt of any investigational HIV vaccine candidate, or HIV monoclonal antibody. Note: receipt of placebo in a previous HIV vaccine or antibody trial will</div>\n <div>\n not exclude a participant from participation if documentation is available and the Medical Monitor gives approval;</div>\n <div>\n 14. History of severe local or systemic reactions to blood or immunoglobulin products or constituents of IPs (e.g., anaphylaxis, respiratory difficulties, angioedema);</div>\n <div>\n 15. Psychiatric condition that compromises the safety of the participant and precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years;</div>\n <div>\n 16. Seizure disorder: A participant who has had a seizure in the last 3 years is excluded;</div>\n <div>\n 17. History of malignancy in the past 5 years or ongoing malignancy (A history of completely excised malignancy that is considered cured is not an exclusion);</div>\n <div>\n 18. Body mass index (BMI) >40;</div>\n <div>\n 19. Active tuberculosis;</div>\n <div>\n 20. If, in the opinion of the Principal Investigator, it is not in the best interest of the participant to participate in the trial.</div>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • primary_end_points<div>\n <strong>Safety and tolerability:</strong></div>\n<div>\n 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.</div>\n<div>\n 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.</div>\n<div>\n 3. Proportion of participants with serious adverse events (SAEs) throughout the study period that are considered related to investigational product and their duration.</div>\n<div>\n  </div>\n<div>\n <strong>Pharmacokinetics (PK):</strong></div>\n<div>\n 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.</div>\n<div>\n  </div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • 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_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p 0px=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n KEMRI-CCR Partners in Health & Research Development - PHRD (Formerly Partners in Prevention) Thika Project, has 64 full time clinical trial staff (including physicians, nurses, counsellors, pharmacist, pharmaceutical technologists, clinical officers, social scientists, administrative staff etc).</p>\n<p 0px=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Principal Investigator: Dr. Nelly R. Mugo  MBChB,MMED,MPH</p>\n<p 0px=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Site Co-Principal Investigator: Dr. Kenneth Ngure  BSc,MPH,MSc,PhD</p>\n<p 0px=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n                                                 Dr. Elizabeth Irungu MBChB, MPH</p>\n<p 0px=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Lead Physician for the study: Dr. Stanley Ndwiga</p>\n<p 0px=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Site Coordinator: Dr. Catherine Kiptinness, BPharm, MPH</p>\n<p 0px=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Regulatory Lead: Peter Mogere</p>\n
      • other_details_explanation<p>\n The study will be conducted in both Kenya and the host country of the sponsor.</p>\n
      • other_details_regulatory_notapproved<p>\n Pan African Clinical Trials Registry - 18 April 2020</p>\n
      • other_details_regulatory_approved<p>\n Kenya Medical Research Institute (SERU) - 25 March 2020</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration3 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_otherYes
      • design_controlled_specifyUnblinded study pharmacy staff at each site will be responsible for investigational product preparation and accountability. All other site staff and all trial participants will be blinded to treatment assignment (i.e., active versus placebo).
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states5
      • number_of_sites2
      • multi_country_list9 clinical trial sites, 3 located in the USA and 6 in Africa (Kenya, Uganda, Rwanda, and South Africa)
      • data_monitoring_committeeYes
      • total_enrolment_per_site28-35 participants
      • total_participants_worldwide225
      • 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_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_nameDagna
      • investigator1_middle_name
      • investigator1_family_nameLaufer
      • investigator1_qualificationMD
      • investigator1_professional_addressInternational AIDS Vaccine Initiative 125 Broad Street, 9th Floor New York, New York 10004
      • investigator1_telephone+1 212-328-7459
      • investigator1_emaildlaufer@iavi.org
      • organisations_transferred_Yes
      • number_participantsThika Site will target to enroll 28-35 participants randomized to study groups 6-10
      • notification
      • approval_date03-03-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted10-06-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe application has been approved by experts
      • final_report<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:709px;\" width=\"709\">\n <tbody>\n <tr>\n <td style=\"width:126px;\">\n <p>\n <strong>Study Title:</strong></p>\n </td>\n <td style=\"width:583px;\">\n <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 </td>\n </tr>\n <tr>\n <td style=\"width:126px;\">\n <p>\n <strong>Prtocol Number:</strong></p>\n </td>\n <td style=\"width:583px;\">\n <p>\n IAVI C100</p>\n <p>\n <strong>ECCT REF</strong>: ECCT<strong>/20/11/02</strong></p>\n <p>\n <strong>ERC REF:</strong> KEMRI/SERU/CCR/0152/3964</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:126px;\">\n <p>\n <strong>Sponsor</strong></p>\n </td>\n <td style=\"width:583px;\">\n <p>\n International AIDS Vaccine Initiative (IAVI)</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:126px;\">\n <p>\n <strong>Study Objectives:</strong></p>\n </td>\n <td style=\"width:583px;\">\n <ul>\n <li>\n <strong>The primary objectives:</strong></li>\n </ul>\n <ol>\n <li>\n To evaluate the safety and tolerability of two broadly neutralizing monoclonal human antibodies, 3BNC117-LS-J and 10-1074-LSJ, when given alone and in combination, intravenously (IV) or subcutaneously (SC) to healthy American and African adults.</li>\n <li>\n 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.</li>\n <li>\n To identify a regimen of the two antibodies that, when given SC every 3 months, will maintain a serum trough level of >10 μg/mL for each antibody in >80% of the study population.</li>\n </ol>\n <ul>\n <li>\n <strong>Secondary objectives:</strong>\n <ol>\n <li>\n To evaluate the effect of participant characteristics, e.g., sex, body weight or body mass index (BMI), on pharmacokinetic parameters.</li>\n <li>\n To conduct pharmacokinetic modelling to assess the effect of dose, dose ratio, dosing frequency and loading dose on serum trough levels of each antibody.</li>\n <li>\n To assess the incidence and titers of anti-drug antibodies (ADA) against each antibody.</li>\n </ol>\n </li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:126px;\">\n <p>\n <strong>Study Design</strong></p>\n </td>\n <td style=\"width:583px;\">\n <p>\n The study was a randomized, double-blind, placebo-controlled Phase 1/2 study intended to evaluate the safety and pharmacokinetics of 10-1074-LS-J and 3BNC117-LS-J, alone or in combination, in healthy American and African adults.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:126px;\">\n <p>\n <strong>Study Population</strong></p>\n </td>\n <td style=\"width:583px;\">\n <p>\n The study population consists of healthy American and African adults, ages 18-45 years who meet all protocol inclusion criteria and do not meet any protocol exclusion criteria and who understand the study and provide written informed consent.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:126px;\">\n <p>\n <strong>Key Findings</strong></p>\n </td>\n <td style=\"width:583px;\">\n <p>\n <strong>Enrollment and Follow-Up:</strong></p>\n <ul>\n <li>\n <strong>Screened: </strong>345 participants.</li>\n <li>\n <strong>Enrolled:</strong> 185 participants, and 184 received the IP</li>\n <li>\n <strong>Completed follow up</strong>: 180 participants</li>\n </ul>\n <p>\n <strong>Safety and Tolerability:</strong></p>\n <ul>\n <li>\n Both IPs (3BNC117-LS-J and 10-1074-LS-J) demonstrate acceptable safety profiles at all administered dose levels (subcutaneous and intravenous).</li>\n <li>\n There were no deaths, related serious adverse events, potential immune mediated events or study discontinuations due to AEs, regardless of relationship to study treatment.</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:126px;\">\n <p>\n <strong>Conclusions and Implications</strong></p>\n </td>\n <td style=\"width:583px;\">\n <ul>\n <li>\n The study confirms that 3BNC117-LS-J and 10-1074-LS-J are safe to use with no major side effects.</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • implication_results<p>\n None.</p>\n
      • quantity_imported270
      • quantity_dispensed188
      • quantity_destroyed72
      • quantity_exportedNone
      • balance_siteNone
      • final_date0000-00-00
      • modified2025-03-25 16:00:20
      • created2020-04-08 10:04:35
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id537
        • application_id868
        • given_nameNelly
        • middle_name
        • family_nameMugo
        • qualificationMBChB, MPH
        • professional_addressKEMRI - CCR Mbagathi way
        • telephone+254 (733) 629 665
        • emailrwamba@uw.edu
        • created2020-04-18 12:47:55
        • modified2021-06-10 11:11:18
    • SiteDetail(array)
      • 0(array)
        • id747
        • application_id868
        • county_id22
        • site_namePartners in Health Research and Development (PHRD) – CCR-KEMRI
        • physical_addressOAU Road, Thika Section 9
        • contact_details+254 (733) 629 665
        • contact_personDr. Nelly Mugo
        • site_capacity(null)
        • misc(null)
        • created2020-04-18 12:47:55
        • modified2021-06-10 11:11:18
        • County(array)
          • id22
          • county_nameKiambu
          • created2012-06-15 10:24:37
          • modified2012-06-15 10:24:37
      • 1(array)
        • id748
        • application_id868
        • county_id47
        • site_nameKenya AIDS Vaccine Initiative- Institute of Clinical Research (KAVI-ICR)
        • physical_addressUniversity of Nairobi
        • contact_details+254 722207417
        • contact_personGaudensia Mutua
        • site_capacity(null)
        • misc(null)
        • created2020-04-18 16:22:37
        • modified2021-06-10 11:11:18
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id425
        • application_id868
        • sponsorInternational AIDS Vaccine Initiative (IAVI)
        • sponsor_typeOthers
        • contact_personDagna Laufer
        • address125 Broad Street, 9th Floor New York, New York 10004 USA
        • telephone_number+1 212-328-7459
        • fax_number
        • cell_number+1 215-852-6674
        • email_addressdlaufer@iavi.org
        • created2020-04-18 12:47:55
        • modified2021-06-10 11:11:18
  • 2(array)
    • Application(array)
      • id1421
      • user_id838
      • trial_status_id2
      • abstract_of_study<div>\n Shigella species are one of the leading causes of diarrhea in our region affecting primarily</div>\n<div>\n infants and children under 5 years of age. Diarrheal diseases account for close to half a</div>\n<div>\n million under five deaths per year worldwide. Following an acute infection, shigellosis is</div>\n<div>\n associated with post infective complications, developmental repercussions, cognitive</div>\n<div>\n impairment and a negative impact on growth. We propose to confirm the immunogenicity and</div>\n<div>\n safety of the second generation of the Shigella bioconjugate vaccine. Shigella4V2 is</div>\n<div>\n composed of O-antigen polysaccharides (PS) from the four different Shigella strains</div>\n<div>\n representing the most epidemiologically relevant serotypes: S. sonnei, S. flexneri 2a, 3a, and</div>\n<div>\n 6, conjugated to the exoprotein A of P. aeruginosa (EPA). All four serotypes included in this</div>\n<div>\n product have already been evaluated and have been found to be safe and immunogenic in</div>\n<div>\n Kenyan infants. We want to confirm these results in the second generation Shigella</div>\n<div>\n bioconjugate, which includes an optimized S. sonnei component, and to select one</div>\n<div>\n formulation out of the two doses which performed the best (immunogenicity- and safetywise)</div>\n<div>\n in the S4V01 trial. Therefore, we will conduct a double blind, single-site trial at</div>\n<div>\n KEMRI’s Clinical Research Center at Siaya County Referral Hospital in western Kenya. We</div>\n<div>\n will evaluate immunogenicity and safety in 110 infants aged 9 ± 1 months. Participants will</div>\n<div>\n be randomised into 3 different arms: 2 investigational groups (12 or 24 μg PS doses including</div>\n<div>\n Alum) and 1 one control group (MenACWY). Study participants will receive 2 doses three</div>\n<div>\n months apart, will undergo a total of 8 visits in clinic, and will be part of the trial for</div>\n<div>\n approximately 9 months.</div>\n
      • study_title<div>\n Safety and immunogenicity of a second generation Shigella bioconjugate vaccine: a phase II randomized, controlled, and blinded study in 9-month-old infants</div>\n
      • laymans_summary<div>\n <u><strong>Lay Title</strong></u></div>\n<div>\n <strong>A study to expand safety and immunogenicity data with the second generation of the Shigella bioconjugate tetravalent (Shigella4V2) in 9-month-old Kenyan infants.</strong></div>\n<div>\n <strong>What is the problem/background?</strong></div>\n<div>\n Bioconjugates are “glycoproteins-like” vaccines made using bacterial cells, and developed at LimmaTech</div>\n<div>\n Biologics (LMTB) through a well established process, that has generated more than 7 products</div>\n<div>\n successfully tested in 10 clinical trials (Table 1). Generally, vaccination with bioconjugates in around 2000</div>\n<div>\n participants ranging from adults to infants has been reported as safe and well tolerated. This trial will</div>\n<div>\n evaluate a vaccine against Shigella, a disease of major importance for children/infants in low and middle</div>\n<div>\n income countries (LMICs). According to the Global Burden of Disease 2019, diarrheal diseases (DDs) are</div>\n<div>\n the fourth leading cause of death for children under 5 years. The impact of DDs goes well beyond</div>\n<div>\n mortality, causing a significant amount of disease that mostly affects children under 5 years of age.</div>\n<div>\n Shigella is the leading pathogen causing DD in LMICs in children > 1 year of age and the second cause of</div>\n<div>\n diarrhea in children under 5 years (1). A clinical phase I/II trial (NCT04056117) using the first generation</div>\n<div>\n (Shigella4V) of this bioconjugate vaccine (Shigella4V2) has already been conducted in Kenya enrolling</div>\n<div>\n around 600 participants, mostly infants but also adults and children. The results of this study showed that</div>\n<div>\n the Shigella4V bioconjugate is safe and immunogenic in the target population of 9 months infants for all 4</div>\n<div>\n vaccine serotypes. Following the positive results, a 2nd generation S. sonnei bioconjugate has been</div>\n<div>\n produced to further increase yield leading to the development of the Shigella4V2 vaccine being used in the</div>\n<div>\n upcoming S4V02 study. This second generation vaccine also comes preformulated with AL(OH)3 adjuvant</div>\n<div>\n and, for enabling multidose presentations, 2-Phenoxyethanol as a preservative, making this Shigella 4V2</div>\n<div>\n drug product phase III ready.</div>\n<div>\n <strong>What questions are we trying to answer?</strong></div>\n<div>\n Following the good safety and immunogenicity data obtained in the phase I/II with Shigella4V, this new</div>\n<div>\n trial aims to expand and confirm the available data in Kenyan infants (9 ± 1 months old) , including the</div>\n<div>\n optimized S. sonnei bioconjugate component. Testing the 2 doses, considering all serotypes, showing the</div>\n<div>\n best immunogenicity following the S4V01 trial (see section 0), we will confirm which of these 2 doses</div>\n<div>\n will be selected for phase III by looking at the vaccine immunogenicity and safety.</div>\n<div>\n <strong>Where is the study taking place, how many people does it involve and how are they selected?</strong></div>\n<div>\n The study is being carried out by KEMRI at their Clinical Research Center located at the Siaya County</div>\n<div>\n Referral Hospital, western Kenya. We aim to recruit healthy participants. Exclusion will include</div>\n<div>\n conditions such as HIV, hepatitis B and C, heart and lung conditions, amongst others. Unlike the S4V01</div>\n<div>\n study, which was the first-in-human trial and was therefore designed in two steps using an age-descending</div>\n<div>\n and dose escalation approach, this study will be conducted in infants only and with concurrent</div>\n<div>\n randomization to either of the two vaccine doses or to the control. A total of 110 infants will be enrolled .</div>\n<div>\n  </div>\n<div>\n <strong>What does the study involve for those who are in it?</strong></div>\n<div>\n Individuals who pass screening examination and meet the eligibility criteria will be consented for</div>\n<div>\n voluntary participation and then enrolled in the study. Screening will involve a series of blood tests to</div>\n<div>\n check for good health. All participants will have pre-test counselling for Hepatitis B and C and HIV-1/2 as</div>\n<div>\n per local practices and recommended national guidelines.</div>\n<div>\n For individuals who are selected for participation, blood will be drawn at the different time-points</div>\n<div>\n according to the Schedule of Events. These samples will range between 5ml and 12ml over approximately</div>\n<div>\n 9 months. Should there be any vaccination visits (V1) occurring within one week from screening (VS),</div>\n<div>\n blood collection at V1 could be omitted because of the proximity with blood draw that occurred at</div>\n<div>\n screening. For these cases, baseline values from screening will be used for further analyses unless there is</div>\n<div>\n any clinical concern or change in medical history in which case relevant investigations would be repeated</div>\n<div>\n (e.g., haematology or biochemistry). Repeat blood samples may be taken to verify abnormal results.</div>\n<div>\n Medical history will also be obtained in addition to undergoing a clinical assessment. Listening to the heart</div>\n<div>\n will serve as an assessment of heart function with further investigations if clinically indicated. Study</div>\n<div>\n participants who pass screening and are eligible to take part in the study will be enrolled in the trial. Those</div>\n<div>\n who don’t, if due to a clinically significant condition, will be counselled as appropriate and then referred to</div>\n<div>\n relevant clinics for further management in line with the local referral systems. Eligible participants will be</div>\n<div>\n randomised to receive either Shigella4V2 or a control vaccine. Blood will be taken at screening, prior to</div>\n<div>\n vaccination (to check baseline antibodies against Shigella serotypes included in the vaccine), and at 2 or 3</div>\n<div>\n time points post each vaccination in order to check 1701 for safety and evaluate the study participants immune</div>\n<div>\n response to vaccination. There will be a total of 6 clinic visits, plus home visits whenever needed in the</div>\n<div>\n week following each vaccination. Should a participant develop diarrhea during the course of the study, 4ml</div>\n<div>\n of blood will be collected to check immune response, together with a stool sample to determine if diarrhea</div>\n<div>\n was caused by Shigella. Free treatment will be provided according to antibiotic susceptibility test results</div>\n<div>\n and as further advised by Kenya’s Ministry of Health guidelines on Control and Management of</div>\n<div>\n Diarrhoeal Diseases in Children Below Five Years. The study duration for each participant will be</div>\n<div>\n approximately 9 months. As previously done in the S4V01 phase I/II trial, at its first administration,</div>\n<div>\n Shigella4V2 will be co-administered with the measles-rubella vaccine in infants which is routinely given</div>\n<div>\n at 9 months of age. Several trials have shown an acceptable safety profile and non-inferiority in the</div>\n<div>\n immune-response when conjugate vaccines are co-administrated together with the measles and rubella</div>\n<div>\n vaccine, and this was also reported in our phase I trial with the Shigella bioconjugate.</div>\n<div>\n  </div>\n<div>\n <strong>What are the benefits and risks/costs of the study for those involved?</strong></div>\n<div>\n It is expected that the Shigella4V2 bioconjugate will lead to further significant progress in the prevention</div>\n<div>\n of Shigella infections caused by the O-antigen serotypes of S. sonnei and S. flexneri 2a, 3a and 6. This</div>\n<div>\n investigational vaccine is no longer in the early stages of clinical development, as efficacy of the</div>\n<div>\n tetravalent first generation product (Shigella4V) has already been demonstrated in the same population.</div>\n<div>\n The anticipated benefits for participants participating in the S4V02 trial may include the following:</div>\n<div>\n  • Participants will contribute to the further advancement of medical and scientific knowledge</div>\n<div>\n  on a candidate Shigella vaccine that may have in the future a key role in the prevention of a disease</div>\n<div>\n  for which there is a high medical burden in LMICs.</div>\n<div>\n  • Participants will benefit from receiving free regular health checks and medical care access</div>\n<div>\n  to the clinic during the entire study although this will be primarily for risk monitoring</div>\n<div>\n  • All participants in the investigational groups will be offered a licensed vaccine (namely</div>\n<div>\n  MenACWY) not included in the regular EPI schedule (Men ACWY is the S4V02 study control</div>\n<div>\n vaccine administered during the study to the control groups and at the end of study to those</div>\n<div>\n participants that received Shigella4V2), without costs.</div>\n<div>\n <strong>How will the study benefit society?</strong></div>\n<div>\n Diarrhea is a big problem all around the world and there is a need to develop vaccines for vulnerable</div>\n<div>\n populations such as infants and children under 5 years, particularly in endemic areas. Furthermore, the</div>\n<div>\n emergence of resistance among Shigella isolates to commonly used antibiotic agents limits the therapeutic</div>\n<div>\n options in some settings. Vaccines can reduce the use of antibiotics and can curb the spread of</div>\n<div>\n antimicrobial resistance in the society. This study will confirm immunogenicity and safety of Shigella4V2,</div>\n<div>\n and will provide information for the subsequent stages of its clinical development. The S4V01 study has</div>\n<div>\n already shown this vaccine to be safe and immunogenic against Shigella flexneri serotypes 2a, 3a, 6 and S.</div>\n<div>\n sonnei. This has given reason to believe that this product is a promising candidate Shigella vaccine</div>\n<div>\n There will also be wider benefit in the field of Shigella vaccine development and in building on data</div>\n<div>\n available on safety and immune responses to the Shigella bioconjugate, which is currently the most</div>\n<div>\n advanced vaccine candidate against Shigella. All 4 components of the vaccine have already been tested in</div>\n<div>\n adults, children, and infants during the S4V01 trial (see Investigator’s Brochure for more details) . Out of</div>\n<div>\n the four bioconjugates included in Shigella4V2, three are the same previously tested with Shigella4V in</div>\n<div>\n the phase I/II S4V01 trial, the fourth bioconjugate is an optimised version of the previously tested S.</div>\n<div>\n sonnei component (O-antigen structure and protein carrier are the same, but product yield has been</div>\n<div>\n improved by increasing number of glycosides on the protein carrier, see IB for further details). In addition,</div>\n<div>\n 6 very similar bioconjugate vaccines have also already been evaluated in around 1500 healthy adults and</div>\n<div>\n have been found to be safe and elicit a good immune response.</div>\n<div>\n  </div>\n<div>\n <strong>When does the study start and finish?</strong></div>\n<div>\n The study will start on receipt of ethical and regulatory approvals and will take approximately 1 year until Last Subject Last Visit.</div>\n<div>\n  </div>\n
      • short_titleS4V02
      • protocol_noECCT/24/08/02
      • version_no1.2
      • date_of_protocol27-05-2024
      • study_drugTetravalent product composed of: O antigenpolysaccharides of S. sonnei and S. flexneri 2a, 3a and 6 conjugated to the recombinant Pseudomonas aeruginosa Exoprotein A, rEPA (Shigella4V2)
      • 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
      • comparator_registeredYes
      • comparator_countriesAustria, Belize, Canada, Chile, Cyprus, Denmark, Estonia, Finland, France, Germany, Great Britain, Greece, Hong Kong, Honduras, Hungary, Indonesia, Israel, Korea (South), Libya, Lithuania, Luxembourg, Latvia, Malta, Malaysia, Netherlands, Norway, Philippines, Poland, Portugal, Qatar, Saudi Arabia, Singapore, Slovak Republic, Spain, Sweden, Switzerland, Turkey, United States
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressomorerichard@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantRichard Omore
      • declaration_date106-08-2024
      • declaration_principal_investigatorRichard Omore
      • declaration_date206-08-2024
      • placebo_presentNo
      • study_objectives<ol>\n <li>\n <div>\n Confirm safety and immunogenicity of Shigella4V2 following two vaccine administration in 9-month-old infants.</div>\n </li>\n <li>\n <div>\n To further evaluate safety of Shigella4V2 through collection of laboratory values from safety laboratory tests.</div>\n </li>\n</ol>\n<p>\n  </p>\n
      • principal_inclusion_criteria<div>\n  </div>\n<div>\n 1. Female or male aged 9 months (± 1 month) old at the time of the first vaccination.</div>\n<div>\n 2. Born full-term (i.e., after a gestation period of 37 to less than 42 full weeks).</div>\n<div>\n 3. Healthy by medical history, laboratory findings and physical examination before entering</div>\n<div>\n into the study (Participants with a minor illness (such as mild diarrhoea, mild upper respiratory</div>\n<div>\n infection) without fever may be enrolled at the discretion of the investigator.</div>\n<div>\n 4. Seronegative for HIV, hepatitis B and C (as per screening laboratory tests).</div>\n<div>\n 5. Resident of Siaya County during the whole trial period.</div>\n<div>\n 6. Previously completed routine primary vaccinations (6,10 and 14 weeks or thereabouts) to the</div>\n<div>\n best knowledge of the participant’s parent/guardian. This information will be abstracted from</div>\n<div>\n the maternal and child health booklet. All the participant’s parent/guardian will be requested</div>\n<div>\n to carry this booklet whenever they visit the clinic.</div>\n<div>\n 7. Signed/thumb printed informed consent, in accordance with local practice, provided by</div>\n<div>\n participants’ parents or guardian who, in the opinion of the investigator, can and will comply with</div>\n<div>\n the requirements of the protocol.</div>\n<div>\n 8. Demonstrated comprehension (by the parent/guardian) of the protocol procedures through</div>\n<div>\n passing a written/verbal comprehension test with a score of 80% or higher (at least 10 out of 12</div>\n<div>\n questions).</div>\n
      • principal_exclusion_criteria<div>\n 1. Any clinically significant deviation from the normal range in biochemistry or</div>\n<div>\n haematological blood tests.</div>\n<div>\n 2. Suspected or known hypersensitivity (including allergy) to any of the vaccine components</div>\n<div>\n or to previous vaccine, or to medicinal products or medical equipment whose use is foreseen in this</div>\n<div>\n study</div>\n<div>\n 3. Clinical conditions representing a contraindication to intramuscular vaccination and blood</div>\n<div>\n draws</div>\n<div>\n 4. Any confirmed or suspected immunosuppressive or immune-deficient condition.</div>\n<div>\n 5. Systemic administration of corticosteroids (PO/IV/IM): prednisone ≥20 mg/day, or</div>\n<div>\n equivalent for more than 14 consecutive days from birth within 90 days prior to informed consent.</div>\n<div>\n Inhaled except for doses > 800 mg/day and topical steroids are allowed.</div>\n<div>\n 6. Administration of antineoplastic or radiotherapy from birth / within 90 days prior to</div>\n<div>\n informed consent. Participants may be on chronic or as needed medications if, in the opinion of the</div>\n<div>\n site principal investigator or appropriate sub-investigator, they pose no additional risk to participant</div>\n<div>\n safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of</div>\n<div>\n medical diagnosis or condition</div>\n<div>\n 7. Known exposure to Shigella during lifetime of the study participant</div>\n<div>\n 8. Concurrently participating in another clinical study, or participation in the preceding month,</div>\n<div>\n at any time during the study period, in which the participant has been or will be exposed to an</div>\n<div>\n investigational or a non-investigational vaccine/product (pharmaceutical product or device).</div>\n<div>\n 9. Acute illness with or without fever is a temporary exclusion criterium. Positive malaria test is a</div>\n<div>\n temporary exclusion criterion.</div>\n<div>\n Note: Following a positive test, participant will be treated for malaria. After the end of treatment,</div>\n<div>\n participant will come to site and be tested again. Following a negative test result for malaria, the</div>\n<div>\n participant will become eligible for enrollment.</div>\n<div>\n 10. History of any malignancy of lymphoproliferative disorder</div>\n<div>\n 11. Parent/guardian known to be part of study personnel or being a close family member to the</div>\n<div>\n personnel conducting this study.</div>\n<div>\n 12. Previous history of significant persistent neutropenia, or drug related Neutropenia</div>\n<div>\n 13. Weight-for-age Z score less than -3SD.</div>\n<div>\n 14. History of any chronic or progressive disease (e.g., neoplasm, insulin dependent diabetes,</div>\n<div>\n cardiac, renal or hepatic disease) that according to judgment of the investigator could interfere with</div>\n<div>\n the study outcomes or pose a threat to the participant's health.</div>\n<div>\n 15. Administration of immunoglobulin and/or any blood products within the three months</div>\n<div>\n preceding the first dose of study vaccine.</div>\n<div>\n 16. Any medical, social condition, or occupational reason that, in the judgment of the</div>\n<div>\n investigator, is a contraindication to protocol participation or impairs the parent’s/guardian’s ability</div>\n<div>\n to give informed consent, increases the risk to the potential participant because of participation in</div>\n<div>\n the study, affect the ability of the volunteer to participate in the study or impair interpretation of the</div>\n<div>\n study data.</div>\n
      • primary_end_points<div>\n Safety:</div>\n<div>\n Safety and tolerability of the candidate vaccine Shigella4V2 as determined by occurrence, severity, and relationship of solicited and unsolicited adverse events (AEs) and serious AEs (SAEs), through:</div>\n<div>\n - solicited local and systemic AEs during the 7 days (day 0 until day 6) following each vaccination.</div>\n<div>\n - unsolicited AEs during 28 days following each vaccination</div>\n<div>\n - SAEs and medically relevant AEs throughout the study</div>\n<div>\n  </div>\n<div>\n <div>\n Immunogenicity:</div>\n <div>\n Evaluation of geometric mean titres (GMT) and geometric mean ratios between baseline and 1- month post 2nd vaccination (GMR vs baseline) for serum IgG against the four Shigella serotypes included in the Shigella4V2 bioconjugate.</div>\n</div>\n<p>\n  </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_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong>Trial Staff</strong></p>\n<p>\n Richard Omore, PhD - Principal Investigator (PI)</p>\n<p>\n <span style=\"text-align: -webkit-center;\">Sidney Ogolla, PhD - Trial Manager</span></p>\n<p>\n <span style=\"text-align: -webkit-center;\">Raphael Anyango - </span>Trial Coordinator</p>\n<p>\n Walter Otieno, MD, PhD - Peditrician</p>\n<p>\n Patricia Ojwang MD - Peditrician</p>\n<p>\n Dennis Bii, MD</p>\n<p>\n Flavia Munga  - Trial Pharmacist </p>\n<p>\n Nypha Myayi - Pharmaceutical Technologist </p>\n<p>\n Prisca Akinyi - Clinical officer</p>\n<p>\n Rebecca Oketch - Clinical officer</p>\n<p>\n Nurse – Sharon Makhoha</p>\n<p>\n Benedict Omondi - QC</p>\n<p>\n Alex Ondeng - QA</p>\n<p>\n Marjorie Audi - Regulatory officer</p>\n<p>\n Bryan Nyawanda - Trial Statistician</p>\n<p>\n Billy Ogwel - Data Manager</p>\n<p>\n Benjamin Ochieng, PhD - Laboratory Director</p>\n<p>\n Kephas Otieno - Laboratory Manager</p>\n<p>\n Caleb Okonji - Community Liaison Officer</p>\n<p>\n Synthia Arek - Community Interviewers</p>\n<p>\n Gordon Onyando - Community Interviewers</p>\n<p>\n Felix Otieno - Community Interviewers</p>\n<p>\n Ivy Akinyi - Community Interviewers</p>\n<p>\n Isaih - Community Interviewers</p>\n<p>\n Joan Lelei - Administrative Officer</p>\n<p>\n  </p>\n<p>\n <strong>Clinical</strong></p>\n<p>\n The clinical department is staffed with well trained and experienced pediatricians and physicians. They provide medical care to the study participants enrolled into trials and support the training of staff on clinical management of the pediatric population, monitoring and reporting of any adverse events related to the vaccine product. In addition, we also have clinical officers and nurses that offer clinical services and procedures by documenting all aspects of patient clinical care. They also administer the IP to the enrolled participants and together with the study pediatrician and MO, they are responsible for implementing trial safety monitoring, follow-up, documenting, reporting and evaluation of adverse events and SAE’s.</p>\n<p>\n <strong>Laboratory</strong></p>\n<p>\n The Siaya CRC laboratory is equipped with hematology and biochemistry-automated analyzers used for safety laboratory monitoring and participants care. The laboratory complies with Good Clinical and Laboratory Practice (GCLP) standards. Laboratory assays used for participants screening, safety monitoring, study endpoint e.g. hematology and biochemistry are registered in external quality assurance (EQA) program with UKNEQAS and Collage of America Pathologist (CAP) respectively just to mention a few. The CRC labs have periodic audits and receives external quality control assessment.</p>\n<p>\n At the KEMRI-CGHR campus, there are state of the art GCLP compliant laboratories. The various laboratory departments are operated by trained, experienced and competent laboratory technicians, research officers and directors, all with GCLP certification. A separate laboratory department of ~500 sq. ft is dedicated for molecular work where diagnostic technologies such as TaqMan Array Cards (TAC) for multi-pathogen detection is located. Another ~500 sq. ft laboratory is a dedicated BSL-2 laboratory. Equipment in place includes dedicated BSL-2 containment laminar flow hoods, CO 2 incubators, ELISA readers, BioRad Imagers and Magpix system. Another ~500 sq. ft is a dedicated microbiology lab. Biosafety cabinets, incubators, fridges, -20 and -80 freezers, autoclaves, centrifuges, block heaters, water baths and PCR workstation are available in this laboratory. Another ~500 sq. ft laboratory is a dedicated BSL-3 laboratory for handling highly infectious microorganisms. All these laboratory departments are connected to standby generators and the fridges and -80 freezers have daily temperature monitoring logs with a 24 hours remote monitoring system. All specimens follow a strict chain of custody from sample collection, shipment (both local and international), logging, testing and archiving, and electronic tracking using a laboratory information management system (LIMS).</p>\n<p>\n <strong>Pharmacy</strong></p>\n<p>\n We have a pharmacy that is managed by qualified pharmacists. Qualified Pharmaceutical technologists are also available and work together with the pharmacists. Our main pharmacy is in Kisumu city. We also have another pharmacy at the Clinical Research Center at the clinical site (Siaya County Referral Hospital), that also have fridges and freezers for storing the IP. These are well maintained and temperature are closely monitored.</p>\n<p>\n Once study participants have been consented, the IP is packed and transported under temperature-controlled environment (in a Credocube-<a href=\"https://www.tardigrad.net/en/products/showproduct/249\">https://www.tardigrad.net/en/products/showproduct/249</a>) to the clinical site. Once at the clinical site pharmacy, the IP is transferred to the fridges until use. The pharmacy has other calibrated and well- maintained fridges and freezers that are in use. Additionally, the temperature in all the fridges and freezers are remotely monitored and logged.</p>\n<p>\n The facilities have backup generators that are automatically powered on once the main electricity goes off. These backup generators are also well maintained through regular servicing.</p>\n<p>\n <strong>Capacity to manage and store clinical data securely:</strong></p>\n<p>\n We use electronic data capture systems which rely on the high-speed internet connectivity that exist in Kenya. This system supports real time data transmission from the FCTS to the data center based at CGHR and other data coordinating centers globally. The electronic questionnaires are either;</p>\n<p style=\"margin-left:36.0pt;\">\n a) developed using Microsoft Visual Studio .NET mapped to a Microsoft SQL Server as the backend, or</p>\n<p style=\"margin-left:36.0pt;\">\n b) use RedCap data capture system.</p>\n<p>\n All these systems operate with multi-level password protection from data entry, transmission, and storage. A customized safe File Transfer Protocol (FTP) system exists based on individual project needs.</p>\n<p>\n Data is transmitted from the tablets at the FCTS to a restricted access and multi-level password protected server housed at the KEMRI-CGHR offices on a daily basis through a Virtual Private Network (VPN). The VPN enables end-to-end encryption of data thus ensuring data security. Data is then managed in password-protected databases. All passwords are managed by the specific data management team leads who are responsible for giving access to other study staff depending on hierarchies and responsibilities within the individual trials. Data management staff generate summaries on a daily/weekly/monthly basis. These summaries are cross-checked with the summaries generated by the study coordinators and any differences resolved as needed. They are also used by the study/trial PI and co-investigators to monitor and ensure trial progress as per protocol in real-time.</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p align=\"center\">\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p align=\"center\">\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p align=\"center\">\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_explanation<div>\n Diarrhoeal diseases (DDs) are common in low-middle-income countries (LMICs) with poor access to clean water, sanitation, and urgent medical care. Shigellosis in particular accounts for 13.2% of all DDdeaths globally and is responsible for approximately 212,000 annual deaths. Mortality rates remain high, with diarrhoea killing almost half a million children under 5 years old each year worldwide. According to the GBD study, diarrhoea is the fourth leading cause of death for children and is responsible for 8.6% of all deaths of children aged under 5. Shigella remains among the leading pathogens strongly associated with both moderate-tosevere</div>\n<div>\n diarrhoea (MSD) and less severe diarrhoeal illness especially in the second year of life. The recent Global Enteric Multicenter Study (GEMS) has shown that about half of all children aged 12-59 months who died with non-dysenteric MSD were positive for Shigella. MSD attributed fraction (AF) to Shigella in GEMS Kenya increased from 4.5% (in infants) to 4.6% in toddlers (12-23 months), and was 9.6% in children aged 24-59 months.</div>\n<div>\n In Kenya, children with diarrhoea with a Shigella infection were more than six times more likely to die than their counterparts without Shigella. Shigella is also, together with nontyphoidal Salmonella, the bacterium most associated with mortality among rural Kenyan children with diarrhoea who access a hospital</div>\n<div>\n The impact of diarrhoeal disease (DD) goes well beyond mortality, causing a significant amount of disability and morbidity that mostly affects children under 5.</div>\n<div>\n Shigellosis or Shigella spp infections are a major cause of diarrhoea combined with fever and enteric symptoms worldwide. It is mainly endemic in developing countries, affecting principally infants, children, and travellers who visit those countries. </div>\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 None</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration2 years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorMenveo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaSiaya County Referral Hospital
      • single_site_physical_addressSiaya County Referral Hospital
      • single_site_contact_personRaphael Ochieng
      • single_site_telephone+254726211172
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_site110
      • total_participants_worldwide110
      • 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_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersYes
      • subjects_others_specifyInfants
      • investigator1_given_nameSidney Ogolla
      • investigator1_middle_name
      • investigator1_family_nameOgolla
      • investigator1_qualificationPhD
      • investigator1_professional_addressKEMRI CGHR P.O BOX 1578 KISUMU 40100
      • investigator1_telephone0723678426
      • investigator1_emailSOOgolla@kemri.go.ke
      • organisations_transferred_Yes
      • number_participants110
      • notification<p style=\"margin-left:54.75pt;\">\n <em>Please note that  we have uploaded CVs for the following investigators under notificatications #15-23 in response to item #4 of the PPB response comments for your review. </em></p>\n<p style=\"margin-left:54.75pt;\">\n <em>Sidney Ogolla, Bryan Nyawanda, Benjamin Ochieng, Kephas Otieno, Boniface Ariera, Billy Ogwel, Raphael Ochieng, and Caleb Okonji are scientists and data specialists who support this trial. As required by section 1.36.1 of the guidelines, they are qualified by </em><em>relevant training and experience within their professional areas that do not necessarily require licenses. The evidence of their qualifications and experience stated in their CVs  uploaded under notifications.</em></p>\n<p style=\"margin-left:54.75pt;\">\n  </p>\n<p style=\"margin-left:54.75pt;\">\n Kind Regards,</p>\n<p>\n  </p>\n
      • approval_date07-01-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted06-08-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted06-08-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonSatisfactory response to ECCT review comments. Application approved
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-03-20 10:54:10
      • created2024-06-18 10:47:56
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1078
        • application_id1421
        • given_nameRichard
        • middle_name
        • family_nameOmore
        • qualificationPhD
        • professional_addressKEMRI CGHR P.O BOX 1578 KISUMU 40100
        • telephone0728813788
        • emailronyando@kemri.go.ke
        • created2024-06-18 12:03:46
        • modified2024-11-12 00:13:33
    • SiteDetail(array)
      • 0(array)
        • id1724
        • application_id1421
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2024-06-18 12:03:46
        • modified2024-11-12 00:13:33
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id754
        • application_id1421
        • sponsorLimmaTech Biologics AG
        • sponsor_typeIndustry
        • contact_personPatricia Martin, PhD
        • addressGrabenstrasse 3 8952 Schlieren Switzerland
        • telephone_number+41 (0)44 733 85 85
        • fax_number
        • cell_number+41 (0)44 733 85 63
        • email_addresspatricia.martin@lmtbio.com
        • created2024-06-18 12:03:46
        • modified2024-11-12 00:13:33
  • 3(array)
    • Application(array)
      • id1386
      • user_id693
      • trial_status_id1
      • abstract_of_study<div>\n Respiratory syncytial virus (RSV) is the most important cause of severe acute lower respiratory illness in infants and children and the most common cause of severe</div>\n<div>\n pneumonia requiring hospital admission in children worldwide. According to global estimates, RSV caused approximately 33 million cases of lower respiratory illness and approximately 118,000 deaths in children < 5 years of age in 2015.Infants and young children are at increased risk for RSV infections because of their maturing immune system and lack of prior exposure to RSV.</div>\n<div>\n A genetically stable live-attenuated RSV ΔNS2/Δ1313/I1314L vaccine has been shown to be safe and immunogenic in RSV-seronegative children in Phase I studies with further research ongoing in RSV-seropositive children. Sanofi is conducting clinical studies with a similar RSV ΔNS2/Δ1313/I1314L vaccine, referred to as RSVt vaccine, as part of the Phase III development of the RSVt vaccine (the VAD0004 study).</div>\n<div>\n  </div>\n<div>\n The VAD0004 study, is a Phase III, randomized, observer-blind, placebo-controlled, multi-center, multinational study to evaluate the efficacy, immunogenicity, and safety of a Respiratory Syncytial Virus vaccine in infants and toddlers. The study is designed to evaluate the efficacy, immunogenicity, and safety of RSVt vaccine administered by intranasal route and compared to placebo.</div>\n<div>\n Overall, a global sample size of approximately 6300 participants 6 months to < 22 months of age will be enrolled in the study. Kenya site will enroll approximately 1500 participants. Eligible participants will be randomized in a 1:1 ratio to receive 2 intranasal administrations of either the RSVt vaccine or placebo.Study duration will be 24months for each participant. The safety evaluation will start after the first vaccination and up to the end of the study. The trial will target recruitment of people from different races and ethnic groups that at a minimum will be representative of the countries in which the trial will be conducted.</div>\n
      • study_title<div>\n Phase III, randomized, observer-blind, placebo-controlled, multi-center, multinational study to evaluate the efficacy, immunogenicity, and safety of a Respiratory Syncytial Virus vaccine in infants and toddlers (PEARL</div>\n
      • laymans_summary<div>\n Respiratory Syncytial Virus (RSV) is a contagious virus (germ) that circulates particularly during the winter months and throughout the year in some parts of the world. It is transmitted through droplets containing the virus when someone infected sneezes or coughs. In most infants, the RSV infection will be a mild illness similar to a cold, with symptoms such as fever, runny nose, sore throat, ear infection, cough, and croup (barky cough with hoarseness). In some cases, RSV can cause serious lung illnesses such as pneumonia and bronchiolitis (an infection of small airways in the lung called bronchioles), which may lead to hospitalization. At this time, there is no approved vaccine to prevent RSV illness.</div>\n<div>\n  </div>\n<div>\n Sanofi Pasteur is developing a vaccine called the RSVt vaccine. The study is called VAD00004 and is a Phase III trial, with two study arms, multiple research sites in multiple countries. in Kenya there are a total of 7 sites. It will be conducted in infants and toddlers 6 months to less than 22 months of age to evaluate if the vaccine works, how safe it is and how the human body responds to protect itself following vaccination of 2 intranasal spray of RSVt vaccine. The trial is designed to demonstrate how the vaccine works in preventing the occurrence of respiratory syncytial Virus.</div>\n<div>\n  </div>\n<div>\n The investigational RSVt vaccine in this study contains a live, weakened form of the virus (that is, attenuated) and is given as a nasal spray. It is made to help a person’s body respond in a way that will protect them from getting sick from the virus. The vaccine has been tested in humans before, and other live attenuated RSV vaccines very similar to this one has also been tested in both adults and children.</div>\n<div>\n A total of 6300 children are planned to be enrolled worldwide. Eligible participants will be randomized in a 1:1 ratio to receive 2 intranasal administrations 56 days apart of either the RSVt vaccine or placebo at day 1 and day 57 of the study. Additional illness visits may occur during the study for those who develops RSV like symptoms. Each participant will be followed for 24 months in the study. Kenya will enroll approximately 15000 up to 1000 children.</div>\n<div>\n  </div>\n<div>\n The trial will target recruitment of people from different races and ethnic groups that at a minimum will be representative of the countries in which the trial will be conducted.</div>\n
      • short_titlePEARL RSVt Vaccine Study
      • protocol_noECCT/24/03/02
      • version_noVersion 2.0
      • date_of_protocol30-06-2023
      • study_drugRSVt _ Dr Oyieko Janet
      • disease_conditionRespiratory syncytial virus (RSV)
      • 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_addressPPDSubmissionsMembers.SM@ppd.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantMillicent Aketch
      • declaration_date106-03-2024
      • declaration_principal_investigatorDr Fredrick Sawe
      • declaration_date206-03-2024
      • placebo_presentYes
      • study_objectives<div>\n Efficacy</div>\n<div>\n 1. To demonstrate the clinical</div>\n<div>\n efficacy of RSVt vaccine for</div>\n<div>\n the prevention of RT-PCR</div>\n<div>\n confirmed RSV LRTD after</div>\n<div>\n 2 doses, over RSV Season 1</div>\n<div>\n Secondary Objective</div>\n<div>\n Efficacy</div>\n<div>\n 1. To demonstrate the clinical efficacy of RSVt vaccine for</div>\n<div>\n the prevention of RT-PCR confirmed RSV URTD after2 doses over RSV Season† 1</div>\n<div>\n 2. To demonstrate the clinical efficacy of RSVt vaccine for</div>\n<div>\n the prevention of RT-PCR confirmed RSV associated</div>\n<div>\n with the occurrence of LRTD, leading to hospitObjectives Endpoints</div>\n<div>\n 3. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV severe LRTD after</div>\n<div>\n 2 doses over RSV Season 1</div>\n<div>\n 4. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV LRTD after</div>\n<div>\n 2 doses over RSV Season 1, necessitating urgent care</div>\n<div>\n 5. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT PCR confirmed RSV ARD after 2 doses</div>\n<div>\n over RSV Season 1</div>\n<div>\n 6. To describe the clinical efficacy of RSVt vaccine for</div>\n<div>\n the prevention of RT-PCR confirmed RSV ARD after</div>\n<div>\n 2 doses over RSV Season 1, leading to hospitalization</div>\n<div>\n 7. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV ARD after 2 doses</div>\n<div>\n over RSV Season 1, necessitating urgent care</div>\n<div>\n 8. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV LRTD, by RSV</div>\n<div>\n strain after 2 doses over RSV Season 1</div>\n<div>\n 9. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV URTD, by RSV</div>\n<div>\n strain after 2 doses over RSV Season 1</div>\n<div>\n 10. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV ARD, by RSV</div>\n<div>\n strain after 2 doses over RSV Season 1</div>\n<div>\n 11. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV LRTD after at least</div>\n<div>\n one dose, over RSV Season 1</div>\n<div>\n 12. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n Pharmaceutical</div>\n<div>\n form</div>\n<div>\n Route of administration</div>\n<div>\n Composition, apart from active</div>\n<div>\n substance(s)</div>\n<div>\n Is it otherwise identical to the</div>\n<div>\n INDP?</div>\n<div>\n If not, specify major</div>\n<div>\n ingredients</div>\n<div>\n 1</div>\n<div>\n Liquid for nasal spray</div>\n<div>\n Intranasal</div>\n<div>\n Histidine-based formulation buffer (including monosodium glutamate, sodium chloride and L-histidine)</div>\n<div>\n Yes</div>\n<div>\n prevention of RT-PCR confirmed RSV URTD after at least</div>\n<div>\n one dose, over RSV Season 1</div>\n<div>\n 13. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV ARD after at least</div>\n<div>\n one dose, over RSV Season 1</div>\n<div>\n 14. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV LRTD after 2</div>\n<div>\n doses over RSV Season 2</div>\n<div>\n 15. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV URTD after 2</div>\n<div>\n doses over RSV Season 2</div>\n<div>\n 16. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV ARD after 2 doses</div>\n<div>\n over RSV Season 2</div>\n<div>\n Safety</div>\n<div>\n 17. To describe the safety profile of the RSVt vaccine</div>\n<div>\n Immunogenicity</div>\n<div>\n 18. To describe the RSV A and B serum neutralizing and RSV</div>\n<div>\n serum anti-F IgA and IgG antibody responses to the study</div>\n<div>\n intervention</div>\n<div>\n Exploratory</div>\n<div>\n Efficacy Efficacy</div>\n<div>\n 1. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV URTD after 2</div>\n<div>\n doses over RSV Season 1, leading to outpatient medical</div>\n<div>\n care, urgent care, or hospitalization.</div>\n<div>\n 2. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV URTD after 2</div>\n<div>\n doses over RSV Season 1, leading to outpatient medical</div>\n<div>\n care</div>\n<div>\n 3. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV ARD after 2 doses</div>\n<div>\n over RSV Season 1, leading to outpatient medical care</div>\n<div>\n 4. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV LRTD after 2</div>\n<div>\n doses over RSV Season 2, leading to hospitalization</div>\n<div>\n 5. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV severe LRTD after</div>\n<div>\n 2 doses over RSV Season 2</div>\n<div>\n 6. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV ARD after 2 doses</div>\n<div>\n over RSV Season 2, leading to hospitalization</div>\n<div>\n 7. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of all-cause acute otitis media (AOM) after 2</div>\n<div>\n doses over RSV Season 1 and Season 2.</div>\n<div>\n Long-Term Immunogenicity</div>\n<div>\n 8. To describe the RSV A and B serum neutralizing and RSV</div>\n<div>\n serum anti-F IgA and IgG antibody responses to the study</div>\n<div>\n intervention at 3 months, 6 months, 1 year and 1.5 years</div>\n<div>\n after dose 2</div>\n<div>\n Immunogenicity</div>\n<div>\n 9. To estimate an immunological correlate of protection</div>\n<div>\n against RT-PCR confirmed RSV LRTD</div>\n<div>\n Safety</div>\n<div>\n 10. To assess the evidence of vaccine-enhanced RSV disease</div>\n<div>\n upon natural infection during both RSV Season 1 and RSV</div>\n<div>\n Season 2</div>\n<div>\n 10. Presence of Grade 1, 2, and 3 LRTD or ARD episodes (during both RSV Season 1 and RSV</div>\n<div>\n Season 2) associated with any RT-PCR confirmed RSV strain</div>\n<div>\n Other</div>\n<div>\n 11. To describe in each study intervention group the following</div>\n<div>\n events that are associated with cases of RT-PCR confirmed</div>\n<div>\n RSV ARD, associated with any RSV strain, over Season 1:</div>\n<div>\n â–ª recurrent wheezing</div>\n<div>\n â–ª pneumonia</div>\n<div>\n â–ª bronchiolitis</div>\n<div>\n â–ª AOM</div>\n<div>\n â–ª febrile illness</div>\n
      • principal_inclusion_criteria<div>\n Participants are eligible for the study only if all of the following criteria are met:</div>\n<div>\n AGE</div>\n<div>\n 1. Aged 6 months to < 22 months on the day of inclusion</div>\n<div>\n  </div>\n<div>\n  </div>\n<div>\n  </div>\n
      • principal_exclusion_criteria<div>\n MEDICAL CONDITIONS</div>\n<div>\n  </div>\n<div>\n E01. Known or suspected congenital or acquired immunodeficiency; or receipt of</div>\n<div>\n immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within</div>\n<div>\n the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or</div>\n<div>\n equivalent for more than 2 consecutive weeks within the past 3 months)</div>\n<div>\n E02. Known systemic hypersensitivity to any of the study intervention components, or history</div>\n<div>\n of a life-threatening reaction to the study intervention used in the study or to a product</div>\n<div>\n containing any of the same substances</div>\n<div>\n E03. Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere</div>\n<div>\n with study conduct or completionc</div>\n<div>\n E04. History of medically diagnosed wheezing</div>\n<div>\n E05. Any acute febrile illness in the past 48 hours that according to investigator judgment is</div>\n<div>\n significant enough to interfere with successful inoculation on the day of vaccination. A</div>\n<div>\n prospective participant should not be included in the study until the condition has resolved</div>\n<div>\n or the febrile event has subsided.</div>\n<div>\n E06. Probable or confirmed ongoing case of viral respiratory infection (including COVID-19,</div>\n<div>\n influenza, rhinovirus, etc.) at the time of enrollment. A prospective participant should not</div>\n<div>\n be included in the study until the respiratory infection has resolved.</div>\n<div>\n E07. Member of a household that contains an immunocompromised individual, including, but</div>\n<div>\n not limited to:</div>\n<div>\n • a person who is HIV infected</div>\n<div>\n • a person who has received chemotherapy within the 12 months prior to study</div>\n<div>\n enrollment</div>\n<div>\n • a person who has received (within the past 6 months) or is receiving (at the time of</div>\n<div>\n enrollment) immunosuppressant agents</div>\n<div>\n • a person living with a solid organ or bone marrow transplant</div>\n<div>\n Potential close contact with other immunocompromised individual within 30 days after</div>\n<div>\n each vaccination as per investigator’s discretion</div>\n<div>\n  </div>\n<div>\n PRIOR/CONCOMITANT THERAPY</div>\n<div>\n E08. Participant’s biological mother’s previous receipt or planned administration of an</div>\n<div>\n investigational RSV vaccine during pregnancy and/or breastfeeding.</div>\n<div>\n E09. Receipt or planned receipt of any of the following vaccines prior to enrollment or after the</div>\n<div>\n first study intervention administration:</div>\n<div>\n • Any other intranasal live attenuated vaccine within the 28 days prior to and after Dose</div>\n<div>\n 1 study administration</div>\n<div>\n • Unless given on the day of Dose 1 study administration, any other injectable live</div>\n<div>\n attenuated vaccines within the 28 days prior to and after. Concomitant receipt on the</div>\n<div>\n day of Dose 1 study administration is allowed.</div>\n<div>\n E10. Previous receipt of an investigational RSV vaccine or receiving any anti-RSV product</div>\n<div>\n (such as ribavirin or RSV immune globulin) at the time of enrollment. Previous receipt of</div>\n<div>\n an RSV monoclonal antibody within 6 months prior to the first study vaccine</div>\n<div>\n administration.</div>\n<div>\n E11. Receipt of immune globulins, blood or blood-derived products in the past 3 months</div>\n<div>\n E12. Receipt of intranasal and intra-ocular medications within 3 days prior to study enrollment</div>\n<div>\n PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE</div>\n<div>\n E13. Participation at the time of study enrollment or planned participation during the present</div>\n<div>\n study period in another clinical study investigating a vaccine, drug, medical device, or</div>\n<div>\n medical procedure</div>\n<div>\n  </div>\n<div>\n OTHER EXCLUSIONS</div>\n<div>\n  </div>\n<div>\n E14. Deprived of freedom in an emergency setting, or hospitalized involuntarily</div>\n<div>\n E15. Identified as a natural or adopted child of the Investigator or employee with direct</div>\n<div>\n involvement in the proposed study</div>\n
      • primary_end_points<div>\n Efficacy</div>\n<div>\n 1. Occurrence of LRTD (during RSV</div>\n<div>\n Season 1) associated with any RT-PCR</div>\n<div>\n confirmed RSV strain > 21 days post-dose 2</div>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • 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
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n KEMRI CCR-Butere</div>\n<div>\n  </div>\n<div>\n The site is housed within the premises of Butere County Hospital (BCH). It is designed to provide preventive and curative care</div>\n<div>\n for patients and has the capacity for regulated clinical trials. It has a full clinical laboratory including hematology, chemistry</div>\n<div>\n and microbiology capability. It is located in Butere sub-county, of Kakamega County. The BCH serves as a referral health</div>\n<div>\n facility offering both out-patient and in-patient services. Feeder health facilities include Shikunga, Shiraha, Shitswistwi,</div>\n<div>\n Lukohe, Iranda, Eshimkoko, Shisaba, Mabole, Manyala, Imanga in Butere and Khwisero, Mulwanda. Mundoli, Emusetsa in</div>\n<div>\n Khwisero Sub-County. These referrals account for the approximately 1425 patients seeking care for various medical</div>\n<div>\n conditions per month in the facility.</div>\n<div>\n  </div>\n<div>\n Butere is one of largest sub-counties in Kakamega county. It has a population of approximately 168,780 people, and area of</div>\n<div>\n approximately 210.6 Square Kilometers. It comprises of five Wards namely Marama West, Marama Central, Marenyo- Shianda,</div>\n<div>\n Marama North and Marama South. BCH is located north of the Equator, along Butere-Shiatsala Road off Sabatia town.</div>\n<div>\n  </div>\n<div>\n The population in the study area is primarily black African, and the languages spoken are Luhya, Kiswahili and English. The</div>\n<div>\n sub-county is largely rural with most residents within the area living in farmlands. The households in these areas are mostly</div>\n<div>\n semi-permanent dwellings with minimal modern provision of electricity, hardly any water and sewerage services connected to</div>\n<div>\n these areas. Water supply to the sub-county is supplied by the Kakamega County Water and Sanitation Company which has a</div>\n<div>\n minimal network of water supply to the sub-county. Being a rural area, the commercial activities are mainly subsistence</div>\n<div>\n farming and small-scale trading.</div>\n<div>\n  </div>\n<div>\n N/B</div>\n<div>\n this submission is for Dr Oyieko, Janet, other sites  have been submitted - Dr Lucas, Dr JAoko and Dr Onono.</div>\n<div>\n  </div>\n<div>\n other sites to be submitted are Dr. Kariuki, Dr Walter and Dr Sawe. as explained on the cover letter </div>\n<div>\n  </div>\n
      • other_details_explanation<p>\n The study will also be done in USA.</p>\n
      • other_details_regulatory_notapproved<p>\n Kenya, submitted in 09 Sep 2023</p>\n<p>\n Argentina - submitted  04 Oct  2023</p>\n<p>\n Brazil - submitted 23 Feb 2024</p>\n<p>\n Chile  - submitted01 Nov  2023- </p>\n<p>\n Colombia_submitted  08 Sep 2023 </p>\n<p>\n thailand _submitted  02 Oct 2023 </p>\n<p>\n Ghana_submitted  19 Sep 2023 </p>\n
      • other_details_regulatory_approved<p>\n South Africa - submitted 11 Aug 2023- approved 18 Oct 2023 - 9 sites </p>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n none</p>\n
      • other_details_regulatory_halted<p>\n none</p>\n
      • estimated_duration4years. - each participant will be followed up for 24months.
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherYes
      • design_controlled_specifyplacebo
      • design_controlled_comparatorplacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states19 Countries
      • number_of_sites7
      • multi_country_listChina India South Korea Thailand Japan Finland Germany Ghana Kenya South Africa Spain Turkey United Kingdom Brazil\nColombia Honduras Mexico Canada United States (inc. Puerto Rico)
      • data_monitoring_committeeYes
      • total_enrolment_per_sitecompetitive enrollment
      • total_participants_worldwide6300
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornYes
      • 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_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specify6 months to < 22 months of age. Pediatric Population
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Fredrick
      • investigator1_middle_nameSawe
      • investigator1_family_nameSawe
      • investigator1_qualificationMedical doctor
      • investigator1_professional_addressMedical Research Institute/Walter Reed, Hospital Road, Kericho, Kenya
      • investigator1_telephone+254703247902
      • investigator1_emailFredrick.sawe@usamru-k.org
      • organisations_transferred_Yes
      • number_participants1500
      • notification
      • approval_date14-05-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted06-03-2024
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been reviewed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-14 16:49:40
      • created2024-03-06 07:55:17
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1045
        • application_id1386
        • given_nameDr. Janet
        • middle_nameNyawira
        • family_nameOyieko
        • qualificationMedical doctor
        • professional_addressButere Clinical Research Centre
        • telephone+254721996988
        • emailjanet.oyieko@usamru-k.org
        • created2024-03-06 07:56:09
        • modified2024-03-06 15:10:01
    • SiteDetail(array)
      • 0(array)
        • id1680
        • application_id1386
        • county_id37
        • site_nameKEMRI CCR – Butere Clinical Research Centre
        • physical_addressWithin Butere County Hospital
        • contact_detailsP.O. Box 40, 50101 Butere
        • contact_personDr. Janet Nyawira Oyieko
        • site_capacity(null)
        • misc(null)
        • created2024-03-06 07:56:09
        • modified2024-03-06 15:10:01
        • County(array)
          • id37
          • county_nameKakamega
          • created2012-06-15 10:26:29
          • modified2012-06-15 10:26:29
    • Sponsor(array)
      • 0(array)
        • id730
        • application_id1386
        • sponsorSanofi Pasteur Inc.
        • sponsor_typeIndustry
        • contact_personSomnath Mangarule _Global Clinical Development Strategic Expert vaccines.
        • address1541,Avenue Marcel Mérieux 69280 Marcy l’Etoile, France
        • telephone_number+33 (0)6 76 97 20 84
        • fax_number
        • cell_number+33 (0)6 76 97 20 84
        • email_addressSomnath.mangarule@sanofi.com
        • created2024-03-06 07:56:09
        • modified2024-03-06 15:10:01
  • 4(array)
    • Application(array)
      • id1395
      • user_id693
      • trial_status_id6
      • abstract_of_study<div>\n Respiratory syncytial virus (RSV) is the most important cause of severe acute lower respiratory illness in infants and children and the most common cause of severe</div>\n<div>\n pneumonia requiring hospital admission in children worldwide. According to global estimates, RSV caused approximately 33 million cases of lower respiratory illness and approximately 118,000 deaths in children < 5 years of age in 2015.Infants and young children are at increased risk for RSV infections because of their maturing immune system and lack of prior exposure to RSV.</div>\n<div>\n  </div>\n<div>\n A genetically stable live-attenuated RSV ΔNS2/Δ1313/I1314L vaccine has been shown to be safe and immunogenic in RSV-seronegative children in Phase I studies with further research ongoing in RSV-seropositive children. Sanofi is conducting clinical studies with a similar RSV ΔNS2/Δ1313/I1314L vaccine, referred to as RSVt vaccine, as part of the Phase III development of the RSVt vaccine (the VAD0004 study).The VAD0004 study, is a Phase III, randomized, observer-blind, placebo-controlled, multi-center, multinational study to evaluate the efficacy, immunogenicity, and safety of a Respiratory Syncytial Virus vaccine in infants and toddlers. The study is designed to evaluate the efficacy, immunogenicity, and safety of RSVt vaccine administered by intranasal route and compared to placebo.</div>\n<div>\n  </div>\n<div>\n Overall, a global sample size of approximately 6300 participants 6 months to < 22 months of age will be enrolled in the study. Kenya site will enroll approximately 1500 participants. Eligible participants will be randomized in a 1:1 ratio to receive 2 intranasal administrations of either the RSVt vaccine or placebo.Study duration will be 24months for each participant. The safety evaluation will start after the first vaccination and up to the end of the study. The trial will target recruitment of people from different races and ethnic groups that at a minimum will be representative of the countries in which the trial will be conducted.</div>\n
      • study_title<div>\n Phase III, randomized, observer-blind, placebo-controlled, multi-center, multinational study to evaluate the efficacy, immunogenicity, and safety of a Respiratory Syncytial Virus vaccine in infants and toddlers (PEARL</div>\n
      • laymans_summary<div>\n Respiratory Syncytial Virus (RSV) is a contagious virus (germ) that circulates particularly during the winter months and throughout the year in some parts of the world. It is transmitted through droplets containing the virus when someone infected sneezes or coughs. In most infants, the RSV infection will be a mild illness similar to a cold, with symptoms such as fever, runny nose, sore throat, ear infection, cough, and croup (barky cough with hoarseness). In some cases, RSV can cause serious lung illnesses such as pneumonia and bronchiolitis (an infection of small airways in the lung called bronchioles), which may lead to hospitalization. At this time, there is no approved vaccine to prevent RSV illness.</div>\n<div>\n  </div>\n<div>\n Sanofi Pasteur is developing a vaccine called the RSVt vaccine. The study is called VAD00004 and is a Phase III trial, with two study arms, multiple research sites in multiplecountries. in Kenya there are a total of 7 sites. It will be conducted in infants and toddlers 6 months to less than 22 months of age to evaluate if the vaccine works, how safe it is and how the human body responds to protect itself following vaccination of 2 intranasal spray of RSVt vaccine. The trial is designed to demonstrate how the vaccine works in preventing the occurrence of respiratory syncytial Virus.</div>\n<div>\n  </div>\n<div>\n The investigational RSVt vaccine in this study contains a live, weakened form of the virus (that is, attenuated) and is given as a nasal spray. It is made to help a person’s body respond in a way that will protect them from getting sick from the virus. The vaccine has been tested in humans before, and other live attenuated RSV vaccines very similar to this one has also been tested in both adults and children. A total of 6300 children are planned to be enrolled worldwide. Eligible participants will be randomized in a 1:1 ratio to receive 2 intranasal administrations 56 days apart of either the RSVt vaccine or placebo at day 1 and day 57 of the study. Additional illness visits may occur during the study for those who develops RSV like symptoms. Each participant will be followed for 24 months in the study. Kenya will enroll approximately 15000 up to 1000 children.</div>\n<div>\n  </div>\n<div>\n The trial will target recruitment of people from different races and ethnic groups that at a minimum will be representative of the countries in which the trial will be conducted.</div>\n
      • short_titlePEARL RSVt Vaccine Study
      • protocol_noECCT/24/04/02
      • version_noVersion 2.0
      • date_of_protocol30-06-2023
      • study_drugRSVt _ Dr Fredrick Sawe
      • disease_conditionRespiratory syncytial virus (RSV)
      • 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_addressPPDSubmissionsMembers.SM@ppd.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantMillicent Aketch
      • declaration_date111-04-2024
      • declaration_principal_investigatorMillicent.Aketch@ppd.com
      • declaration_date211-04-2024
      • placebo_presentYes
      • study_objectives<div>\n Primary Objective</div>\n<div>\n  </div>\n<div>\n Efficacy</div>\n<div>\n 1. To demonstrate the clinical efficacy of RSVt vaccine for</div>\n<div>\n the prevention of RT-PCR confirmed RSV LRTD after</div>\n<div>\n 2 doses, over RSV Season 1</div>\n<div>\n  </div>\n<div>\n Secondary Objective</div>\n<div>\n Efficacy</div>\n<div>\n 1. To demonstrate the clinical efficacy of RSVt vaccine for</div>\n<div>\n the prevention of RT-PCR confirmed RSV URTD after2 doses over RSV Season† 1</div>\n<div>\n 2. To demonstrate the clinical efficacy of RSVt vaccine for</div>\n<div>\n the prevention of RT-PCR confirmed RSV associated</div>\n<div>\n with the occurrence of LRTD, leading to hospitObjectives Endpoints</div>\n<div>\n 3. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV severe LRTD after</div>\n<div>\n 2 doses over RSV Season 1prevention of RT-PCR confirmed RSV LRTD after</div>\n<div>\n 2 doses over RSV Season 1, necessitating urgent care</div>\n<div>\n 5. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT PCR confirmed RSV ARD after 2 doses</div>\n<div>\n over RSV Season 1</div>\n<div>\n 6. To describe the clinical efficacy of RSVt vaccine for</div>\n<div>\n the prevention of RT-PCR confirmed RSV ARD after</div>\n<div>\n 2 doses over RSV Season 1, leading to hospitalization</div>\n<div>\n 7. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV ARD after 2 doses</div>\n<div>\n over RSV Season 1, necessitating urgent care</div>\n<div>\n 8. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV LRTD, by RSV</div>\n<div>\n strain after 2 doses over RSV Season 1</div>\n<div>\n 9. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV URTD, by RSV</div>\n<div>\n strain after 2 doses over RSV Season 1</div>\n<div>\n 10. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV ARD, by RSV</div>\n<div>\n strain after 2 doses over RSV Season 1</div>\n<div>\n 11. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV LRTD after at least</div>\n<div>\n one dose, over RSV Season 1</div>\n<div>\n 12. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n Pharmaceutical</div>\n<div>\n form</div>\n<div>\n Route of administration</div>\n<div>\n Composition, apart from active</div>\n<div>\n substance(s)</div>\n<div>\n Is it otherwise identical to the</div>\n<div>\n INDP?</div>\n<div>\n If not, specify major</div>\n<div>\n ingredients</div>\n<div>\n 1L</div>\n<div>\n iquid for nasal spray</div>\n<div>\n Intranasal</div>\n<div>\n Histidine-based formulation buffer (including monosodium glutamate, sodium chloride and L-histidine)</div>\n<div>\n Yes</div>\n<div>\n prevention of RT-PCR confirmed RSV URTD after at least</div>\n<div>\n one dose, over RSV Season 1</div>\n<div>\n 13. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV ARD after at least</div>\n<div>\n one dose, over RSV Season 1</div>\n<div>\n 14. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV LRTD after 2</div>\n<div>\n doses over RSV Season 2</div>\n<div>\n 15. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV URTD after 2</div>\n<div>\n doses over RSV Season 2</div>\n<div>\n 16. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV ARD after 2 doses</div>\n<div>\n over RSV Season 2</div>\n<div>\n Safety</div>\n<div>\n 17. To describe the safety profile of the RSVt vaccine</div>\n<div>\n Immunogenicity</div>\n<div>\n 18. To describe the RSV A and B serum neutralizing and RSV</div>\n<div>\n serum anti-F IgA and IgG antibody responses to the study</div>\n<div>\n intervention</div>\n<div>\n Exploratory</div>\n<div>\n Efficacy Efficacy</div>\n<div>\n 1. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV URTD after 2</div>\n<div>\n doses over RSV Season 1, leading to outpatient medical</div>\n<div>\n care, urgent care, or hospitalization.</div>\n<div>\n 2. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV URTD after 2</div>\n<div>\n doses over RSV Season 1, leading to outpatient medical</div>\n<div>\n care</div>\n<div>\n 3. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV ARD after 2 doses</div>\n<div>\n over RSV Season 1, leading to outpatient medical care</div>\n<div>\n 4. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV LRTD after 2</div>\n<div>\n doses over RSV Season 2, leading to hospitalization</div>\n<div>\n 5. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV severe LRTD after</div>\n<div>\n 2 doses over RSV Season 2</div>\n<div>\n 6. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of RT-PCR confirmed RSV ARD after 2 doses</div>\n<div>\n over RSV Season 2, leading to hospitalization</div>\n<div>\n 7. To describe the clinical efficacy of RSVt vaccine for the</div>\n<div>\n prevention of all-cause acute otitis media (AOM) after 2</div>\n<div>\n doses over RSV Season 1 and Season 2.</div>\n<div>\n Long-Term Immunogenicity</div>\n<div>\n 8. To describe the RSV A and B serum neutralizing and RSV</div>\n<div>\n serum anti-F IgA and IgG antibody responses to the study</div>\n<div>\n intervention at 3 months, 6 months, 1 year and 1.5 years</div>\n<div>\n after dose 2</div>\n<div>\n Immunogenicity</div>\n<div>\n 9. To estimate an immunological correlate of protection</div>\n<div>\n against RT-PCR confirmed RSV LRTD</div>\n<div>\n Safety</div>\n<div>\n 10. To assess the evidence of vaccine-enhanced RSV disease</div>\n<div>\n upon natural infection during both RSV Season 1 and RSV</div>\n<div>\n Season 2</div>\n<div>\n 10. Presence of Grade 1, 2, and 3 LRTD or ARD episodes (during both RSV Season 1 and RSV</div>\n<div>\n Season 2) associated with any RT-PCR confirmed RSV strain</div>\n<div>\n Other</div>\n<div>\n 11. To describe in each study intervention group the following</div>\n<div>\n events that are associated with cases of RT-PCR confirmed</div>\n<div>\n <div>\n RSV ARD, associated with any RSV strain, over Season 1:</div>\n <div>\n â–ª recurrent wheezing</div>\n <div>\n â–ª pneumonia</div>\n <div>\n â–ª bronchiolitis</div>\n <div>\n â–ª AOM</div>\n <div>\n â–ª febrile illness</div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<div>\n Participants are eligible for the study only if all of the following criteria are met:</div>\n<div>\n AGE</div>\n<div>\n 1. Aged 6 months to < 22 months on the day of inclusion</div>\n
      • principal_exclusion_criteria<div>\n E01. Known or suspected congenital or acquired immunodeficiency; or receipt of</div>\n<div>\n immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within</div>\n<div>\n the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or</div>\n<div>\n equivalent for more than 2 consecutive weeks within the past 3 months)</div>\n<div>\n E02. Known systemic hypersensitivity to any of the study intervention components, or history</div>\n<div>\n of a life-threatening reaction to the study intervention used in the study or to a product</div>\n<div>\n containing any of the same substances</div>\n<div>\n E03. Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere</div>\n<div>\n with study conduct or completionc</div>\n<div>\n E04. History of medically diagnosed wheezing</div>\n<div>\n E05. Any acute febrile illness in the past 48 hours that according to investigator judgment is</div>\n<div>\n significant enough to interfere with successful inoculation on the day of vaccination. A</div>\n<div>\n prospective participant should not be included in the study until the condition has resolved</div>\n<div>\n or the febrile event has subsided.</div>\n<div>\n E06. Probable or confirmed ongoing case of viral respiratory infection (including COVID-19,</div>\n<div>\n influenza, rhinovirus, etc.) at the time of enrollment. A prospective participant should not</div>\n<div>\n be included in the study until the respiratory infection has resolved.</div>\n<div>\n E07. Member of a household that contains an immunocompromised individual, including, but</div>\n<div>\n not limited to:</div>\n<div>\n • a person who is HIV infected</div>\n<div>\n • a person who has received chemotherapy within the 12 months prior to study</div>\n<div>\n enrollment</div>\n<div>\n • a person who has received (within the past 6 months) or is receiving (at the time of</div>\n<div>\n enrollment) immunosuppressant agents</div>\n<div>\n • a person living with a solid organ or bone marrow transplant</div>\n<div>\n Potential close contact with other immunocompromised individual within 30 days after</div>\n<div>\n each vaccination as per investigator’s discretion</div>\n<div>\n PRIOR/CONCOMITANT THERAPY</div>\n<div>\n E08. Participant’s biological mother’s previous receipt or planned administration of an</div>\n<div>\n investigational RSV vaccine during pregnancy and/or breastfeeding.</div>\n<div>\n E09. Receipt or planned receipt of any of the following vaccines prior to enrollment or after the</div>\n<div>\n first study intervention administration:</div>\n<div>\n • Any other intranasal live attenuated vaccine within the 28 days prior to and after Dose</div>\n<div>\n 1 study administration</div>\n<div>\n • Unless given on the day of Dose 1 study administration, any other injectable live</div>\n<div>\n attenuated vaccines within the 28 days prior to and after. Concomitant receipt on the</div>\n<div>\n day of Dose 1 study administration is allowed.</div>\n<div>\n E10. Previous receipt of an investigational RSV vaccine or receiving any anti-RSV product</div>\n<div>\n (such as ribavirin or RSV immune globulin) at the time of enrollment. Previous receipt of</div>\n<div>\n an RSV monoclonal antibody within 6 months prior to the first study vaccine</div>\n<div>\n administration.</div>\n<div>\n E11. Receipt of immune globulins, blood or blood-derived products in the past 3 months</div>\n<div>\n E12. Receipt of intranasal and intra-ocular medications within 3 days prior to study enrollment</div>\n<div>\n PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE</div>\n<div>\n E13. Participation at the time of study enrollment or planned participation during the present</div>\n<div>\n study period in another clinical study investigating a vaccine, drug, medical device, or</div>\n<div>\n medical procedure</div>\n<div>\n  </div>\n<div>\n OTHER EXCLUSIONS</div>\n<div>\n  </div>\n<div>\n E14. Deprived of freedom in an emergency setting, or hospitalized involuntarily</div>\n<div>\n E15. Identified as a natural or adopted child of the Investigator or employee with direct</div>\n<div>\n involvement in the proposed study</div>\n
      • primary_end_points<div>\n Efficacy</div>\n<div>\n 1. Occurrence of LRTD (during RSV</div>\n<div>\n Season 1) associated with any RT-PCR</div>\n<div>\n confirmed RSV strain > 21 days post-dose 2</div>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyImmunogenicity
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n Kericho Site</div>\n<div>\n  </div>\n<div>\n The U.S. Army Medical Research Directorate-Africa (USAMRD-A) is a Special Foreign Activity of the Walter Reed Army Institute</div>\n<div>\n of Research (WRAIR), Washington, DC. USAMRD- K is affiliated through a Cooperative Agreement with the Kenya Medical</div>\n<div>\n Research Institute (KEMRI). The unit was activated on a temporary basis in 1969 at the invitation of the Government of Kenya</div>\n<div>\n to study trypanosomiasis. The success of that initial venture led to the establishment of a permanent activity in 1973. Over</div>\n<div>\n the past 46 years, research has been conducted on malaria, polio, trypanosomiasis, leishmaniasis, entomology, HIV/AIDS,</div>\n<div>\n enteric diseases and arboviruses, with more than 250 manuscripts published.</div>\n<div>\n  </div>\n<div>\n Kericho is located among the African Highlands in the Kenya’s Rift Valley region and well known for the growing of tea that</div>\n<div>\n forms the rolling “seas of green” within the tea plantations. The primary industry in this region is tea farming, with two large</div>\n<div>\n international tea companies namely Finlay’s Kenya Ltd. and Unilever Tea Kenya Ltd. being centered in Kericho County.</div>\n<div>\n  </div>\n<div>\n Income in Kericho comes mainly from agricultural activities, with about 40-50% of the population living below the poverty line.</div>\n<div>\n The annual national gross domestic product per capita in 2005 averaged Kenyan shillings (Kshs) 35,045 (equivalent to 350.45</div>\n<div>\n United States dollar (USD) at current exchange rates of 1 USD = Ksh 100). According to 2019 population census, Kericho.</div>\n<div>\n  </div>\n<div>\n County has a population of 901,777 and an area of 2,111 km2, with a population density of 365.40 persons/km2. In Kenya, the</div>\n<div>\n age of majority (i.e. legal age of recognized adulthood or independence) is 18 years. The Kenyan national literacy level</div>\n<div>\n according the Kenya Adult Literacy Survey report published in March 2007 by the Kenya National Bureau of Statistics was</div>\n<div>\n 64%. In Kericho, the literacy level is 74.3% in men and 68.9% in women. The healthcare system in the larger Kericho area</div>\n<div>\n (southern Rift Valley) is primarily provided by the government through a network of public hospitals, health centers, and</div>\n<div>\n dispensaries ran by the Kenya Ministry of Health. The government health facilities do not charge for treatment but levy a</div>\n<div>\n small fee for facility maintenance, which can be waived for those not able to pay. In addition to government health care</div>\n<div>\n facilities, there are a few faith based and private health care facilities providing services at a small fee. Access to most health</div>\n<div>\n care facilities is good given that there exist a fairly reliable public transport system in the region.</div>\n<div>\n  </div>\n<div>\n The site has a long-standing experience in conducting several studies including clinical trials, ranging from therapeutics,</div>\n<div>\n vaccines (HIV, Polio, Ebola, Shigella, MERS CoV, Yellow Fever, Hexavalent) and cohort studies. The clinical trials range from</div>\n<div>\n phase I to IV with age ranges from birth to the elderly, some of which are randomized double blind, placebo controlled and</div>\n<div>\n <div>\n United States Investigational New Drug (IND)/ Food and Drug Administration (FDA)-regulated. Both the CRC pharmacy and</div>\n <div>\n laboratory are approved by the National Institute of Allergy and Infectious Diseases/Division of AIDS (NIAID/DAIDS) to</div>\n <div>\n participate in DAIDS sponsored vaccine (Site # 1502) and therapeutics (Site #12501) and International Maternal, Pediatric,</div>\n <div>\n and Adolescent AIDS Clinical Trials (IMPAACT) Group (Site # 5121) studies, the only research site with such approval in Kenya.</div>\n <div>\n The lab is also College of American Pathologists (CAP) accredited and consists of three main sections: Processing and safety,</div>\n <div>\n Microbiology and Mycobacterium tuberculosis (TB).</div>\n <div>\n  </div>\n <div>\n The Kericho CRC is equipped with two emergency rooms (one per floor) with equipment and medications to provide</div>\n <div>\n immediate emergency care in the event of emergencies during vaccinations such as anaphylaxis, convulsions, hypotension,</div>\n <div>\n and provisions (resuscitation equipment) are in place for immediate resuscitation on site. Additionally, the Kericho site has a</div>\n <div>\n standby, fully equipped ambulance for evacuation of participants for more specialized care when necessary. The Kericho</div>\n <div>\n County Referral Hospital, which sits in the same compound as the CRC has an Intensive Care Unit (ICU) which will be utilized</div>\n <div>\n should need arise. The study staffs (clinicians/nurses) are trained on handling emergencies. All study procedures will be done</div>\n <div>\n at KEMRI/USAMRD-A Clinical Research Center, Kericho with additional satellite sites set-up to cater for the anticipated large</div>\n <div>\n number of participants to be enrolled. The site uses UTK hospital as a satellite site for inpatient admissions of participants</div>\n <div>\n needing inpatient services. The hospital is located about two kilometers from the CRC and has both outpatient and inpatient</div>\n <div>\n services.</div>\n</div>\n<div>\n  </div>\n<div>\n N/B  This submission is specififc to Dr Sawe Kericho site , hence other sites detais are not added .</div>\n<div>\n  </div>\n
      • other_details_explanation<p>\n The study will also be done in USA.</p>\n
      • other_details_regulatory_notapproved<div>\n  </div>\n<div>\n Argentina - submitted 04 Oct 2023</div>\n<div>\n Brazil - submitted 23 Feb 2024</div>\n<div>\n Chile - submitted01 Nov 2023-</div>\n<div>\n Colombia_submitted 08 Sep 2023</div>\n<div>\n thailand _submitted 02 Oct 2023</div>\n<div>\n Ghana_submitted 19 Sep 2023</div>\n
      • other_details_regulatory_approved<p>\n South Africa - submitted 11 Aug 2023- approved 18 Oct 2023 - 9 sites</p>\n<p>\n Kenya,Submitted 09 Sep 2023_ First site Approved on  Mar 2024</p>\n
      • other_details_regulatory_rejected<p>\n none</p>\n
      • other_details_regulatory_halted<p>\n none</p>\n
      • estimated_duration4years. - each participant will be followed up for 24months.
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherYes
      • design_controlled_specifyplacebo
      • design_controlled_comparatorplacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states19 Countries
      • number_of_sites7
      • multi_country_listChina India South Korea Thailand Japan Finland Germany Ghana Kenya South Africa Spain Turkey United Kingdom Brazil\nColombia Honduras Mexico Canada United States (inc. Puerto Rico)
      • data_monitoring_committeeYes
      • total_enrolment_per_sitecompetitive enrollment
      • total_participants_worldwide6300
      • 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_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specify6 months to < 22 months of age. Pediatric Population
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Fredrick
      • investigator1_middle_nameKipyego
      • investigator1_family_nameSawe
      • investigator1_qualificationMedica Doctor
      • investigator1_professional_addressMedical Research Institute/Walter Reed, Hospital Road, Kericho, Kenya
      • investigator1_telephone+254703247902
      • investigator1_emailFredrick.sawe@usamru-k.org
      • organisations_transferred_Yes
      • number_participants1500
      • notification<p>\n None </p>\n
      • approval_date03-07-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted11-04-2024
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
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      • quantity_imported(null)
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      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-18 14:07:28
      • created2024-04-11 13:25:24
      • total_sites(null)
      • ecitizen_invoice(null)
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        • id1058
        • application_id1395
        • given_nameDr Fredrick
        • middle_nameKipyego
        • family_nameSawe
        • qualificationMedical doctor
        • professional_addressMedical Research Institute/Walter Reed, Hospital Road, Kericho, Kenya
        • telephone+254703247902
        • emailFredrick.sawe@usamru-k.org
        • created2024-04-11 14:11:45
        • modified2024-04-11 20:23:16
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        • id1694
        • application_id1395
        • county_id35
        • site_nameWalter Reed Army Institute of Research -Kericho Site
        • physical_addressKenya Medical Research Institute/Walter Project - Kericho
        • contact_detailsP.O. Box 1357 – 20200, Hospital Road, Kericho, Kenya
        • contact_personFredrick Sawe
        • site_capacity(null)
        • misc(null)
        • created2024-04-11 14:11:45
        • modified2024-04-11 20:23:16
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          • id35
          • county_nameKericho
          • created2012-06-15 10:26:16
          • modified2012-06-15 10:26:16
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        • id739
        • application_id1395
        • sponsorSanofi Pasteur Inc.
        • sponsor_typeIndustry
        • contact_personSomnath Mangarule _Global Clinical Development Strategic Expert vaccines.
        • address1541,Avenue Marcel Mérieux 69280 Marcy l’Etoile, France
        • telephone_number+33 (0)6 76 97 20 84
        • fax_number
        • cell_number+33 (0)6 76 97 20 84
        • email_addressSomnath.mangarule@sanofi.com
        • created2024-04-11 14:11:45
        • modified2024-04-11 20:23:16
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App Constants

CakePHP Constants

PHP Environment

Included Files

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• 1/var/www/html/ctr/lib
• 3/usr/share/php
• 4-> /var/www/html/ctr/lib/Cake/

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