NCT07379580

Brief Summary

This is a randomized, double-blind, placebo-controlled study which aims to assess the safety, reactogenicity, and immunogenicity after one and two doses of BNT166a or placebo in healthy participants.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
310

participants targeted

Target at P75+ for phase_2

Timeline
13mo left

Started Feb 2026

Shorter than P25 for phase_2

Geographic Reach
2 countries

6 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress16%
Feb 2026Jun 2027

First Submitted

Initial submission to the registry

January 23, 2026

Completed
7 days until next milestone

First Posted

Study publicly available on registry

January 30, 2026

Completed
21 days until next milestone

Study Start

First participant enrolled

February 20, 2026

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2027

Last Updated

March 4, 2026

Status Verified

March 1, 2026

Enrollment Period

1.3 years

First QC Date

January 23, 2026

Last Update Submit

March 2, 2026

Conditions

Mpox (Monkeypox)SmallpoxOrthopoxvirus Infection

Keywords

Monkeypox virus (MPXV)Active immunizationRibonucleic acid (RNA) vaccine

Outcome Measures

Primary Outcomes (9)

  • Number (and percentage) of participants with at least one solicited local reaction (pain, erythema/redness, induration/swelling)

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults.

    For up to 7 days following each dose

  • Number (and percentage) of participants with at least one solicited systemic reaction (fever, headache, fatigue/tiredness, muscle pain/myalgia, joint pain/arthralgia, chills, diarrhea, vomiting)

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults.

    For up to 7 days following each dose

  • Number (and percentage) of participants with at least one use of antipyretics/analgesics

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults.

    For up to 7 days following each dose

  • Number (and percentage) of participants with at least one unsolicited adverse event (AE) (post-Dose 1)

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults.

    From Dose 1 to 28 days post-Dose 1

  • Number (and percentage) of participants with at least one unsolicited AE (post-Dose 2)

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults.

    From Dose 2 to 28 days post-Dose 2

  • Number (and percentage) of participants with at least one serious adverse event

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults.

    From Dose 1 until the end of study, i.e., up to ~14 months

  • Number (and percentage) of participants with at least one AE of special interest

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults.

    From Dose 1 until the end of study, i.e., up to ~14 months

  • Number (and percentage) of participants with at least one medically attended AE

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults.

    From Dose 1 until the end of study, i.e., up to ~14 months

  • Number (and percentage) of participants with at least one AE leading to a participant's withdrawal from the study

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults.

    From Dose 1 until the end of study, i.e., up to ~14 months

Secondary Outcomes (6)

  • Geometric mean titers (GMT) of BNT166a antigen-specific (A35, B6, H3, and M1) binding antibody titers

    At baseline, 1 month post-Dose 1, and 1 month post- Dose 2

  • Geometric mean fold rise (GMFR) of BNT166a antigen-specific (A35, B6, H3, and M1) binding antibody titers

    At 1 month post-Dose 1 and 1 month post-Dose 2

  • GMT of MPXV-specific neutralizing antibody titers

    At baseline, 1 month post-Dose 1, and 1 month post-Dose 2

  • GMFR of MPXV-specific neutralizing antibody titers

    At 1 month post-Dose 1 and 1 month post-Dose 2

  • GMT of vaccinia virus (VACV)-specific neutralizing antibody titers

    At baseline, 1 month post-Dose 1, and 1 month post-Dose 2

  • +1 more secondary outcomes

Study Arms (6)

Cohort 1 - BNT166a Dose Level (DL) 1 (Orthopoxvirus-naïve participants, aged 18-45 years)

EXPERIMENTAL

Two doses of investigational medicinal product (IMP).

Biological: BNT166a

Cohort 1 - BNT166a DL 2 (Orthopoxvirus-naïve participants, aged 18-45 years)

EXPERIMENTAL

Two doses of IMP.

Biological: BNT166a

Cohort 1 - Placebo (Orthopoxvirus-naïve participants, aged 18-45 years)

PLACEBO COMPARATOR

0.9% sodium chloride solution. Two doses of IMP.

Other: Placebo

Cohort 2 - BNT166a DL 1 (Orthopoxvirus-experienced participants, aged 18-64 years)

EXPERIMENTAL

Two doses of IMP.

Biological: BNT166a

Cohort 2 - BNT166a DL 2 (Orthopoxvirus-experienced participants, aged 18-64 years)

EXPERIMENTAL

Two doses of IMP.

Biological: BNT166a

Cohort 2 - Placebo (Orthopoxvirus-experienced participants, aged 18-64 years)

PLACEBO COMPARATOR

0.9% sodium chloride solution. Two doses of IMP.

Other: Placebo

Interventions

BNT166aBIOLOGICAL

Intramuscular injection. Injections should be given in the deltoid muscle, using the same non-dominant arm for all IMP doses.

Cohort 1 - BNT166a DL 2 (Orthopoxvirus-naïve participants, aged 18-45 years)Cohort 1 - BNT166a Dose Level (DL) 1 (Orthopoxvirus-naïve participants, aged 18-45 years)Cohort 2 - BNT166a DL 1 (Orthopoxvirus-experienced participants, aged 18-64 years)Cohort 2 - BNT166a DL 2 (Orthopoxvirus-experienced participants, aged 18-64 years)
PlaceboOTHER

Intramuscular injection. Injections should be given in the deltoid muscle, using the same non-dominant arm for all IMP doses.

Cohort 1 - Placebo (Orthopoxvirus-naïve participants, aged 18-45 years)Cohort 2 - Placebo (Orthopoxvirus-experienced participants, aged 18-64 years)

Eligibility Criteria

Age18 Years - 64 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Are male or female individuals ≥18 years of age at the time of giving informed consent:
  • Cohort 1: ≥18 to ≤45 years of age
  • Cohort 2: ≥18 to ≤64 years of age
  • Cohort 1: Participants must be Orthopoxvirus-naïve (have no history of smallpox or mpox vaccination or mpox infection).
  • Cohort 2: Participants must be Orthopoxvirus-experienced (have evidence of mpox or smallpox vaccination or mpox infection at least 2 years prior to consent).

You may not qualify if:

  • Have had recent exposure to mpox (defined as close contact with a probable or confirmed case of mpox within the past 28 days, or have evidence of mpox infection or mpox vaccination within 2 years prior to consent).
  • Have a contraindication, warning and/or precaution to vaccination with a messenger ribonucleic acid (mRNA) Coronavirus disease 2019 (COVID-19) vaccine as specified in the Summary of Product Characteristics for BNT162b2 (COMIRNATY United States Prescribing Information/European Union Summary of Product Characteristics) and BNT166 Investigator Brochure.
  • Have a history of allergies, hypersensitivities, or intolerance to the study treatments including any excipients thereof.
  • Have a current or history of cardiovascular diseases, e.g., myocarditis, pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy, or clinically significant arrhythmias.
  • Have any known bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  • Have a body mass index ≤18.5 kg/m\^2 or ≥35 kg/m\^2.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

University of Kinshasa UNIKIN

Kinshasa, 01306, Democratic Republic of the Congo

NOT YET RECRUITING

Institute National de Recherche Biomedicale

Kinshasa, 5345, Democratic Republic of the Congo

NOT YET RECRUITING

TASK Applied Science

Cape Town, 7405, South Africa

NOT YET RECRUITING

TREAD Research Pty Ltd

Cape Town, 7530, South Africa

RECRUITING

Desmond Tutu Health Foundation Masiphumelele Clinic

Cape Town, 7975, South Africa

NOT YET RECRUITING

Perinatal HIV Research Unit

Johannesburg, 1864, South Africa

RECRUITING

MeSH Terms

Conditions

Mpox, MonkeypoxSmallpoxPoxviridae Infections

Condition Hierarchy (Ancestors)

DNA Virus InfectionsVirus DiseasesInfectionsPrimate DiseasesAnimal DiseasesRodent Diseases

Study Officials

  • BioNTech Responsible Person

    BioNTech SE

    STUDY DIRECTOR

Central Study Contacts

BioNTech clinical trials patient information

CONTACT

+49 6131 9084patients@biontech.de

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 23, 2026

First Posted

January 30, 2026

Study Start

February 20, 2026

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

June 1, 2027

Last Updated

March 4, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share

Locations

ZA(4)DE(2)