A Randomized, Partially Observer-blind, Dose-escalation, Phase I/II Trial Evaluating the Safety and Immunogenicity of Investigational RNA-based Mpox Vaccine Candidates
Overview
- Phase
- Phase 1
- Intervention
- BNT166a
- Conditions
- Monkeypox
- Sponsor
- BioNTech SE
- Enrollment
- 96
- Locations
- 7
- Primary Endpoint
- SSA, SSB, and SSD - Proportion (%) of participants reporting solicited local reactions at the injection site (pain, erythema/redness, induration/swelling)
- Status
- Active, not recruiting
- Last Updated
- 6 months ago
Overview
Brief Summary
This is a dose-escalation, Phase I/II study evaluating the safety, tolerability, reactogenicity and immunogenicity of the investigational RNA-based multivalent vaccine candidate BNT166a for active immunization against monkeypox (mpox).
This study started with substudy A (SSA) and substudy B (SSB) for which recruitment has been completed. A Substudy C (SSC) was planned, but the sponsor decided not to conduct it. This study will therefore continue with substudy D (SSD).
In SSA and SSB, dosing started with an initial sentinel group, followed by the expansion cohort.
This study was initially planned to investigate two vaccine candidates (the quadrivalent BNT166a and the trivalent BNT166c). The sponsor decided to not activate the groups with BNT166c.
Detailed Description
Substudy A is an open-label, dose-escalation, Phase I substudy to assess the reactogenicity, safety, and immunogenicity of up to three dose levels of the multivalent vaccine candidate BNT166a in 48 healthy participants with no prior history of known or suspected smallpox vaccination (vaccinia-naïve participants). Substudy B is a one group, open-label, Phase I substudy to assess the reactogenicity, safety and immunogenicity of the multivalent vaccine candidate BNT166a in 16 healthy participants with prior history of smallpox vaccination (vaccinia-experienced). Substudy D is a one group, open-label, Phase IIa substudy to assess the reactogenicity, safety, and immunogenicity of one dose level of BNT166a in \~32 healthy participants with no prior history of known or suspected smallpox vaccination (i.e., vaccinia-naïve participants). SSD will be initiated after the interim analysis of SSA and SSB safety, reactogenicity, and immunogenicity data. The duration of study participation is \~ 14 months per participant in all of the substudies.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
SSA - BNT166a Dose Level (DL)1
One dose level
Intervention: BNT166a
SSA - BNT166a DL2
One dose level
Intervention: BNT166a
SSA - BNT166a DL3
One dose level
Intervention: BNT166a
SSB - BNT166a DL2
One dose level
Intervention: BNT166a
SSD - BNT166a
One dose level based on SSA and SSB data
Intervention: BNT166a
Outcomes
Primary Outcomes
SSA, SSB, and SSD - Proportion (%) of participants reporting solicited local reactions at the injection site (pain, erythema/redness, induration/swelling)
Time Frame: From Dose 1 through Day 7 post-Dose1 inclusive; and from Dose 2 through Day 7 post-Dose 2 inclusive
For each group
SSA, SSB, and SSD - Proportion (%) of participants reporting solicited systemic events (vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, and fever)
Time Frame: From Dose 1 through Day 7 post-Dose1 inclusive; and from Dose 2 through Day 7 post-Dose 2 inclusive
For each group
SSA, SSB, and SSD - Proportion (%) of participants with at least one unsolicited adverse event (AE) occurring from Dose 1 through Day 28 post-Dose 1 inclusive
Time Frame: From Dose 1 through Day 28 post-Dose 1 inclusive
For each group
SSA, SSB, and SSD - Proportion (%) of participants with at least one unsolicited AE occurring from Dose 2 through Day 28 post-Dose 2 inclusive
Time Frame: from Dose 2 through Day 28 post-Dose 2 inclusive
For each group
SSA, SSB, and SSD - Proportion (%) of participants with at least one serious adverse event (SAE) occurring from Dose 1 through Day 201 post-Dose 1 inclusive
Time Frame: From Dose 1 through Day 201 post-Dose 1 inclusive
For each group
SSA, SSB, and SSD - Proportion (%) of participants with at least one adverse event of special interest (AESI) occurring from Dose 1 through Day 201 post-Dose 1 inclusive
Time Frame: From Dose 1 through Day 201 post-Dose 1 inclusive
For each group