Tumaini Trial: A Phase 2/3 Randomized, Controlled, Adaptive Platform Trial to Evaluate the Efficacy, Safety, and Immunogenicity of Vaccine Candidates Against Bundibugyo Virus Disease (BVD) in Contact Cases
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 3,810
- 试验地点
- 1
- 主要终点
- Phase 2: Proportion of participants experiencing unsolicited Grade 3 or 4 adverse events, serious adverse events, SUSARs, adverse events of special interest, or medically attended adverse events
研究概览
简要总结
Bundibugyo virus (BDBV) causes severe and often fatal outbreaks of Bundibugyo virus disease (BVD). No vaccine against BDBV is licensed. There is an urgent need to identify vaccines that are safe, immunogenic, and effective in preventing disease among people at highest risk of infection.
This is a Phase 2/3 randomized, double-blind, active-controlled adaptive platform trial evaluating candidate BDBV vaccines in contacts of confirmed BVD cases, co-sponsored by the University of Antwerp and the National Institute of Biomedical Research (INRB), Kinshasa. The contacts of each confirmed index case form a "ring". Eligible contacts are individually randomized to a candidate vaccine or an active comparator on Day 1, and on Day 29 all participants receive the crossover intervention, so that every participant is offered a candidate vaccine while the comparison between groups remains blinded. The platform allows additional candidates to enter as they are prioritized and allows evaluation of a candidate to be discontinued for futility, with an independent Data Monitoring Committee reviewing accumulating data throughout. The overall aim is to generate robust evidence to support the use of BDBV vaccines for outbreak response and future epidemic preparedness.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •A contact of a newly confirmed Bundibugyo virus disease (BVD) index case, occurring within the previous 21 days of enrollment. A contact is defined as a person who, within the previous 21 days, lived in the same household as the index case; OR visited or was visited by the index case at or after the onset of symptoms; OR, without using adequate personal protective equipment, provided the index case with care, was in close physical contact with the patient's body, body fluids, linen or clothes, or prepared the body for, or was exposed to the body at, a funeral ceremony.
- •Adults, adolescents, and children aged 12 years and older at the time of enrollment.
- •Capable of giving signed informed consent or assent, or having a parent or legal guardian capable of giving signed or witnessed verbal informed consent, in accordance with applicable country regulations.
排除标准
- •History of laboratory-confirmed Bundibugyo virus disease.
- •Previous vaccination against Bundibugyo virus. Note: prior receipt of an Ebola or Marburg investigational or licensed vaccine is non-exclusionary provided that any prior vaccination was administered more than 28 days before enrollment and is documented.
- •History of anaphylaxis from a vaccine or a component of a vaccine.
- •Serious bed-confining illness requiring hospitalization at the time of vaccination.
- •Receipt of monoclonal antibodies as post-exposure prophylaxis (PEP) within 21 days prior to vaccination, or planned receipt after vaccination.
- •Ongoing treatment with antiviral PEP at the time of vaccination. Note: prior receipt of a licensed or experimental antiviral candidate for BVD PEP is acceptable provided the course was completed at least six days prior to vaccination. Note: if PEP becomes standard of care, it is non-exclusionary.
- •Use of any other experimental drug, other than antivirals or monoclonal antibodies used for BVD prophylaxis, within 28 days prior to vaccination.
- •Currently enrolled in, or planning to participate in, another investigational or interventional study during this study. Observational and registry studies are permitted.
- •Living in an area deemed inaccessible by the Investigator, for reasons of distance or security.
- •Symptoms consistent with BVD, defined as inexplicable bleeding, OR high fever together with at least three of the following: headache, lethargy, anorexia or loss of appetite, aching muscles or joints, stomach pain, difficulty swallowing, vomiting, difficulty breathing, diarrhea, hiccups.
研究组 & 干预措施
Candidate BDBV vaccine, then a comparator
Participants randomized to this arm receive a single dose of a candidate Bundibugyo virus (BDBV) vaccine on Day 1, administered at the location where the participant resides at the time of vaccination. Eligibility criteria are reconfirmed and body temperature measured before the dose is administered. Participants are observed for 30 minutes after vaccination for immediate adverse events. On Day 29 participants in this arm receive the comparator as a crossover intervention. Dose, formulation and route are candidate-specific and are specified in the vaccine-specific appendix for each candidate entering the platform. Safety follow-up continues to Day 181 in the Phase 2 component and to Day 29 in the Phase 3 component.
干预措施: Candidate BDBV vaccine (Biological)
Candidate BDBV vaccine, then a comparator
Participants randomized to this arm receive a single dose of a candidate Bundibugyo virus (BDBV) vaccine on Day 1, administered at the location where the participant resides at the time of vaccination. Eligibility criteria are reconfirmed and body temperature measured before the dose is administered. Participants are observed for 30 minutes after vaccination for immediate adverse events. On Day 29 participants in this arm receive the comparator as a crossover intervention. Dose, formulation and route are candidate-specific and are specified in the vaccine-specific appendix for each candidate entering the platform. Safety follow-up continues to Day 181 in the Phase 2 component and to Day 29 in the Phase 3 component.
干预措施: Active comparator (Biological)
Comparator, then candidate BDBV vaccine
Participants randomized to this arm receive a single dose of comparator, administered at the location where the participant resides at the time of vaccination. Eligibility criteria are reconfirmed and body temperature measured before the dose is administered. Participants are observed for 30 minutes after administration for immediate adverse events. On Day 29 participants in this arm receive the corresponding candidate BDBV vaccine as a crossover intervention. Safety follow-up continues to Day 181 in the Phase 2 component and to Day 29 in the Phase 3 component.
干预措施: Candidate BDBV vaccine (Biological)
Comparator, then candidate BDBV vaccine
Participants randomized to this arm receive a single dose of comparator, administered at the location where the participant resides at the time of vaccination. Eligibility criteria are reconfirmed and body temperature measured before the dose is administered. Participants are observed for 30 minutes after administration for immediate adverse events. On Day 29 participants in this arm receive the corresponding candidate BDBV vaccine as a crossover intervention. Safety follow-up continues to Day 181 in the Phase 2 component and to Day 29 in the Phase 3 component.
干预措施: Active comparator (Biological)
结局指标
主要结局
Phase 2: Proportion of participants experiencing unsolicited Grade 3 or 4 adverse events, serious adverse events, SUSARs, adverse events of special interest, or medically attended adverse events
时间窗: Day 1 to Day 181
Proportion of vaccine recipients who experience unsolicited Grade 3 or 4 adverse events (AEs), serious adverse events (SAEs), suspected unexpected serious adverse reactions (SUSARs), adverse events of special interest (AESIs), or medically attended adverse events (MAAEs), assessed using severity and causality assessments. Events are summarized with counts, percentages and exact 95% confidence intervals.
Phase 3: Vaccine efficacy against PCR-confirmed symptomatic Bundibugyo virus disease with symptom onset 10 to 29 days after vaccination
时间窗: Day 10 to Day 29 after vaccination
Vaccine efficacy estimated by comparing the number of PCR-confirmed symptomatic Bundibugyo virus disease cases with symptom onset 10 to 29 days after randomization in each candidate vaccine arm with the comparator arm. The primary analysis is per-protocol.
次要结局
- Phase 2: Seroconversion rate measured by ELISA for IgM and IgG titres(Days 1, 15, 29, 43, 57 and 181)
- Phase 3: Number of confirmed Bundibugyo virus disease deaths in each arm(Day 0 to Day 29 after vaccination)
- Phase 3: Number of PCR-confirmed symptomatic Bundibugyo virus disease cases with symptom onset 10 to 29 days after vaccination, modified intention-to-treat(Day 10 to Day 29 after vaccination)
- Phase 3: Number of PCR-confirmed symptomatic Bundibugyo virus disease cases with symptom onset 0 to 9 days after vaccination(Day 0 to Day 9 after vaccination)
研究者
Jean-Pierre Van geertruyden
Sponsor
Universiteit Antwerpen