Safety and Immune Responses After Vaccination With Two Investigational RNA-based Vaccines Against Tuberculosis in BCG Vaccinated Volunteers
- Conditions
- Tuberculosis
- Interventions
- Registration Number
- NCT05547464
- Lead Sponsor
- BioNTech SE
- Brief Summary
This is a two-part randomized, placebo-controlled, observer-blind, safety and dose-finding Phase Ib/IIa study. This study will evaluate up to four dose levels of the BNT164 investigational vaccines (BNT164a1 and BNT164b1) to select a safe and tolerable dose in a three-dose schedule.
This study includes: Part A (Phase Ib) and Part B (Phase IIa).
- Detailed Description
In Part A, enrollment for BNT164a1 and BNT164b1 will be conducted independently and in parallel. Part A of the study will enroll participants into four dose groups per investigational medicinal product (\[IMP\] i.e., BNT164a1 or BNT164b1) who will be stratified by interferon gamma release assay (IGRA) status and then randomized 5:1 for BNT164 (BNT164a1 or BNT164b1):placebo. This part of the study will use a staggered dose escalation schema, i.e., enrollment into the next higher dose level is done sequentially and subject to safety data from the previous dose levels, with sentinel participants for Dose 1 in all dose groups.
In Part B, up to two dose levels for each IMP will be selected for the human immunodeficiency virus (HIV)-negative dose groups based on the safety and immunogenicity data from Part A, as above. The higher of these two dose levels for each IMP will be used in the people living with HIV (PLWH) dose groups.
Part B of this study is a safety expansion to up to two dose groups per IMP (BNT164a1 or BNT164b1) + placebo for HIV-negative participants. Additionally, Part B will include a population expansion into PLWH with up to one dose group per IMP (BNT164a1 or BNT164b1) + placebo. HIV-negative participants will be randomized 3:3:3:3:1 to the four dose groups of BNT164 (BNT164a1 or BNT164b1):placebo. PLWH will be randomized 2:2:1 to the two dose groups of BNT164 (BNT164a1 or BNT164b1):placebo.
In both Part A and Part B, participants will undergo a three-dose injection schedule with approximately 8 weeks between the first and second dose and approximately 16 weeks between the second and third dose.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 492
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Isotonic sodium chloride (NaCl) solution (0.9%) BNT164a1 BNT164a1 Escalating dose levels BNT164b1 BNT164b1 Escalating dose levels
- Primary Outcome Measures
Name Time Method Proportion of participants with at least one adverse event (AE) occurring from each dose to 28 days after each dose From each dose up to 28 days after each dose Part A and Part B
Proportion of participants with at least one serious AE or AE of special interest occurring from Dose 1 up to 168 days post-Dose 3 From Dose 1 up to 168 days post-Dose 3 Part A and Part B. In Part A, from Dose 1 up to 168 days post-Dose 3. In Part B, from Dose 1 up to 28 days post- Dose 3.
Frequency of solicited local reactions (pain, erythema/redness, induration/swelling) at the injection site up to 7 days after each dose Up to 7 days after each dose Part A and Part B
Number of unsolicited AEs from Dose 1 to 28 days post-Dose 3 From Dose 1 up to 28 days post-Dose 3 Part A and Part B
Frequency of solicited systemic reactions (vomiting, diarrhea, headache, fatigue, muscle pain & joint pain, chills, and fever) up to 7 days after each dose Up to 7 days after each dose Part A and Part B
Proportion of participants with at least one unsolicited AE occurring from Dose 1 to 28 days post-Dose 3 From Dose 1 up to 28 days post-Dose 3 Part A and Part B
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (8)
Centro de Investigação em Saúde de Manhiça (CISM)
🇲🇿Manhiça, Mozambique
Africa Health Research Institute (AHRI)
🇿🇦Mtubatuba, South Africa
The Aurum Institute Tembisa CRC Clinic 4
🇿🇦Tembisa, South Africa
Centro de Investigação e Treino em Saúde da Polana Caniço (CISPOC)
🇲🇿Maputo, Mozambique
CAPRISA eThekweni Clinical Research Site
🇿🇦Berea, South Africa
South African Tuberculosis Vaccine Initiative SATVI
🇿🇦Cape Town, South Africa
Centre for Lung Infection and Immunity UCT Lung Institute
🇿🇦Cape Town, South Africa
Desmond Tutu Health Foundation - Masiphumele Research Office
🇿🇦Cape Town, South Africa