ClinicalTrials.gg
RecruitingNCT07379580Updated Aug 11, 2026

A Randomized Clinical Trial Investigating the Safety, Reactogenicity, and Immunogenicity After Immunization With an mRNA-based Mpox Vaccine Candidate in Africa

A Phase 2 interventional study of BNT166a and Placebo in Mpox (Monkeypox), Smallpox and Orthopoxvirus Infection, sponsored by BioNTech SE. Recruiting at 6 sites in 2 countries. Open to participants aged 18 Years to 64 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-11.

Sponsored by BioNTech SE · Phase 2, Interventional, and Prevention

From the registry’s dates

  • Started Feb 2026; still recruiting 8 months later.
Phase
Phase 2
Study type
Interventional
Enrollment
310
Allocation
Randomized
Ages
18 Years to 64 Years
Sex
All
01

Study 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.

Read the detailed description

This study will include the following cohorts:

  • Cohort 1: healthy adults aged 18 to 45 years inclusive who are Orthopoxvirus-naïve.
  • Cohort 2: healthy adults aged 18 to 64 years inclusive who are Orthopoxvirus-experienced.

All participants will receive two doses of BNT166a or placebo at least 28 days apart.

The planned study duration per participant is \~14 months.

02

Conditions studied

  • Mpox (Monkeypox)
  • Smallpox
  • Orthopoxvirus Infection

Keywords

  • Monkeypox virus (MPXV)
  • Active immunization
  • Ribonucleic acid (RNA) vaccine
03

In context

Mpox, Monkeypox

72 studies on the registry are indexed under Mpox, Monkeypox; 30 are open to participants now.

This study's planned enrollment of 310 is close to the median of 305 across 36 interventional studies indexed under Mpox, Monkeypox.

Browse Mpox, Monkeypox studies →

Lead sponsor

BioNTech SE is the lead sponsor of 76 studies on the registry; 25 are open to participants now.

Of its 33 completed or terminated interventional studies of FDA-regulated products, 26 (79%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 64 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Eligibility criteria

Key Inclusion Criteria (applicable to all participants unless otherwise specified):

  • Are male or female individuals ≥18 years of age at the time of giving :

    • 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).

Key Exclusion Criteria (applicable to all participants unless otherwise specified):

  • 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 , 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, , or intolerance to the study treatments including any thereof.
  • Have a current or history of cardiovascular diseases, e.g., myocarditis, pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy, or 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 ≤18.5 kg/m\^2 or ≥35 kg/m\^2.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Terms in these criteria, in plain language(6)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

Excipients

The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
310 participants (estimated)

Study arms

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

    Two doses of investigational medicinal product (IMP).

    Biological: BNT166a

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

    Two doses of IMP.

    Biological: BNT166a

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

    0.9% sodium chloride solution. Two doses of IMP.

    Other: Placebo

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

    Two doses of IMP.

    Biological: BNT166a

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

    Two doses of IMP.

    Biological: BNT166a

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

    0.9% sodium chloride solution. Two doses of IMP.

    Other: Placebo

Interventions

  • BiologicalBNT166a

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

  • OtherPlacebo

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

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: For up to 7 days following each dose

  2. 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.

    Time frame: For up to 7 days following each dose

  3. 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.

    Time frame: For up to 7 days following each dose

  4. 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.

    Time frame: From Dose 1 to 28 days post-Dose 1

  5. 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.

    Time frame: From Dose 2 to 28 days post-Dose 2

  6. 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.

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

  7. 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.

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

  8. 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.

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

  9. 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.

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

Secondary outcomes

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

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults, at the defined timepoints.

    Time frame: At baseline, 1 month post-Dose 1, and 1 month post- Dose 2

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

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults. Ratio post-baseline/baseline at the defined timepoints.

    Time frame: At 1 month post-Dose 1 and 1 month post-Dose 2

  3. GMT of MPXV-specific neutralizing antibody titers

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults, at the defined timepoints.

    Time frame: At baseline, 1 month post-Dose 1, and 1 month post-Dose 2

  4. GMFR of MPXV-specific neutralizing antibody titers

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults. Ratio post-baseline/baseline at the defined timepoints.

    Time frame: At 1 month post-Dose 1 and 1 month post-Dose 2

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

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults, at the defined timepoints.

    Time frame: At baseline, 1 month post-Dose 1, and 1 month post-Dose 2

  6. GMFR of VACV-specific neutralizing antibody titers

    At each dose level of BNT166a in Orthopoxvirus-naïve (Cohort 1) and Orthopoxvirus-experienced (Cohort 2) adults. Ratio post-baseline/baseline at the defined timepoints.

    Time frame: At 1 month post-Dose 1 and 1 month post-Dose 2

07

Study locations

6 of 6 sites recruiting
  • University of Kinshasa UNIKIN
    Kinshasa, 01306, Democratic Republic of the Congo
    Recruiting
  • Institute National de Recherche Biomedicale
    Kinshasa, 5345, Democratic Republic of the Congo
    Recruiting
  • TASK Applied Science
    Cape Town, 7405, South Africa
    Recruiting
  • TREAD Research Pty Ltd
    Cape Town, 7530, South Africa
    Recruiting
  • Desmond Tutu Health Foundation Masiphumelele Clinic
    Cape Town, 7975, South Africa
    Recruiting
  • Perinatal HIV Research Unit
    Johannesburg, 1864, South Africa
    Recruiting
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 11, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07379580
Lead sponsor
BioNTech SE
Collaborators
Coalition for Epidemic Preparedness Innovations
Responsible party
Sponsor
First posted
Jan 30, 2026
Start date
Feb 20, 2026
Primary completion
Jun 2027 (estimated)
Completion
Jun 2027 (estimated)
Last update
Aug 11, 2026

Study contacts

BioNTech clinical trials patient information
Contact
patients@biontech.de
+49 6131 9084 ext. 0
BioNTech Responsible Person
study director · BioNTech SE

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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