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, blinded, 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 alternative 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.
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 1 year and older at the time of enrollment. Where a candidate vaccine has an age indication that does not cover the full age range, enrollment for that candidate is limited to its age indication and compared with the same age group in the comparator arm. The lower age limit for any age band is determined by the age indication of both the candidate vaccine and the comparator.
Capable of giving written informed consent, or having a parent, legal guardian or legally authorized representative capable of giving written informed consent on the participant's behalf, in accordance with applicable country regulations. Where permitted by local regulations, witnessed verbal consent may be obtained for participants unable to provide written consent, documented in the presence of an impartial witness independent of the study team. Participants for whom assent is required under local regulations or ethics committee requirements must additionally provide informed assent.
Willing to provide verifiable identification, such as iris scanning or a participant card where feasible, and able to be contacted by telephone number or address.
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.
Acute unstable illness at the time of vaccination, including organ failure, severe ongoing infection, or any acute condition requiring hospitalization.
Parallel
Candidate BDBV vaccine
Biological/VaccineCandidate Bundibugyo Virus (BDBV) vaccine - A candidate Bundibugyo virus vaccine recommended for prioritization by the independent World Health Organization Technical Advisory Group on Candidate Vaccines Prioritization. Administered as a single dose. Dose, formulation and route are candidate-specific and are specified in the vaccine-specific appendix for each candidate entering the platform. Additional candidate vaccines may be added to the platform as they become available and meet the inclusion criteria.
Active comparator
Biological/VaccineActive comparator, Typhoid vaccine. All study interventions are reconstituted and dispensed by an uninvolved third party, such as a trial pharmacist, so that allocation remains masked.
Phase 2: Proportion of participants experiencing serious adverse events, suspected unexpected serious adverse reactions, adverse events of special interest, or medically attended adverse events
Proportion of vaccine recipients who experience 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 polymerase chain reaction (PCR)-confirmed symptomatic Bundibugyo virus disease with symptom onset 10 to 29 days after vaccination
Vaccine efficacy estimated by comparing the number of polymerase chain reaction (PCR)-confirmed symptomatic Bundibugyo virus disease cases with symptom onset 10 to 29 days after vaccination in each candidate vaccine arm with the comparator arm. The primary analysis is per-protocol.
Phase 2: Proportion of participants experiencing unsolicited adverse events, Grade 1 to Grade 4
Proportion of vaccine recipients who experience unsolicited adverse events of any grade (Grade 1 to Grade 4), assessed using severity and causality assessments. Events are summarized with counts, percentages and exact 95% confidence intervals.
Phase 2: Seropositivity and seroconversion rates measured by Bundibugyo virus glycoprotein-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and pseudovirus neutralization assay (pVNA)
Seropositivity and seroconversion rates assessed in all participants in each candidate vaccine arm and in the comparator group randomized alongside that candidate. Endpoints are Bundibugyo virus (BDBV) glycoprotein-specific immunoglobulin G (IgG) concentrations measured by enzyme-linked immunosorbent assay (ELISA), and functional titers measured by pseudovirus neutralization assay (pVNA). Samples are collected from all participants at every time point to preserve masking. Analysis is aligned to the timing of candidate vaccine receipt in each group.
Phase 3: Number of confirmed Bundibugyo virus disease deaths in each arm
Number of deaths from confirmed Bundibugyo virus disease in each arm, compared between each candidate vaccine arm and the comparator arm. The denominator for each arm is the number of participants randomized to that arm.
Phase 3: Number of polymerase chain reaction (PCR)-confirmed symptomatic Bundibugyo virus disease cases with symptom onset 10 to 29 days after vaccination, modified intention-to-treat
Number of polymerase chain reaction (PCR)-confirmed symptomatic Bundibugyo virus disease cases with symptom onset 10 to 29 days after vaccination in each arm, analyzed as modified intention-to-treat, to estimate vaccine efficacy between each candidate vaccine arm and the comparator arm.
Phase 3: Number of polymerase chain reaction (PCR)-confirmed symptomatic Bundibugyo virus disease cases with symptom onset 0 to 9 days after vaccination
Number of polymerase chain reaction (PCR)-confirmed symptomatic Bundibugyo virus disease cases with symptom onset 0 to 9 days after vaccination in each arm, used to estimate vaccine efficacy in the period before protection is expected to be established.
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Jean-Pierre Van geertruyden
Lead sponsor
Universiteit Antwerpen
Sponsor institution
Institute of Tropical Medicine, Belgium
Collaborator
Institut National de Recherche Biomedicale (INRB)
Collaborator
Epicentre
Collaborator
Médecins Sans Frontières, Belgium
Collaborator
World Health Organization
Collaborator
Coalition for Epidemic Preparedness Innovations
Collaborator
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