A Clinical Study Investigating the Safety and Immune Responses After Immunization With Investigational Monkeypox Vaccines

NCT05988203 | Completed Phase 1 FDA Drug

• 2 other identifiers: BNT166-011006947
• Study Type: interventional
• Target: 96
• Locations: 2 countries
• Sites: 9

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.

Conditions

Monkeypox

Keywords

Prevention of mpox; Monkeypox virus; RNA vaccine; Vaccine; mpox; MPXV; Monkeypox

Outcome Measures

Primary Outcomes (6)

• SSA, SSB, and SSD - Proportion (%) of participants reporting solicited local reactions at the injection site (pain, erythema/redness, induration/swelling)

  For each group

  From Dose 1 through Day 7 post-Dose1 inclusive; and from Dose 2 through Day 7 post-Dose 2 inclusive

• SSA, SSB, and SSD - Proportion (%) of participants reporting solicited systemic events (vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, and fever)

  For each group

  From Dose 1 through Day 7 post-Dose1 inclusive; and from Dose 2 through Day 7 post-Dose 2 inclusive

• 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

  For each group

  From Dose 1 through Day 28 post-Dose 1 inclusive

• SSA, SSB, and SSD - Proportion (%) of participants with at least one unsolicited AE occurring from Dose 2 through Day 28 post-Dose 2 inclusive

  For each group

  from Dose 2 through Day 28 post-Dose 2 inclusive

• 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

  For each group

  From Dose 1 through Day 201 post-Dose 1 inclusive

• 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

  For each group

  From Dose 1 through Day 201 post-Dose 1 inclusive

Study Arms (5)

SSA - BNT166a Dose Level (DL)1

EXPERIMENTAL

One dose level

Biological: BNT166a

SSA - BNT166a DL2

EXPERIMENTAL

One dose level

Biological: BNT166a

SSA - BNT166a DL3

EXPERIMENTAL

One dose level

Biological: BNT166a

SSB - BNT166a DL2

EXPERIMENTAL

One dose level

Biological: BNT166a

SSD - BNT166a

EXPERIMENTAL

One dose level based on SSA and SSB data

Biological: BNT166a

Interventions

BNT166a BIOLOGICAL

Multivalent ribonucleic acid (RNA)-based vaccine for active immunization against monkeypox administered as intramuscular injection.

SSA - BNT166a DL2; SSA - BNT166a DL3; SSA - BNT166a Dose Level (DL)1; SSB - BNT166a DL2; SSD - BNT166a

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have given informed consent by signing and dating the informed consent form (ICF) before initiation of any study-specific procedures.
• Are willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study, including the prohibited concomitant medications. This includes that they are able to understand and follow study-related instructions.
• SSA and SSD only: Are 18 through 45 years of age (inclusive) at the time of informed consent.
• SSB only: Are 50 through 65 years of age (inclusive) at the time of informed consent.
• Have a body mass index over 18.5 kg/m\^2 and under 30 kg/m\^2 and weigh at least 50 kg at Visit 0.
• Are healthy, in the clinical judgment of the investigator based on volunteer-reported medical history data, physical examination, 12-lead electrocardiogram (ECG), vital signs, and clinical laboratory test results.
• SSA and SSD only: Have no prior history of known or suspected smallpox vaccination and no detectable smallpox vaccination characteristic scar (vaccinia-naïve participants).
• SSB only: Have a history of prior smallpox vaccination (i.e., are vaccinia-experienced), determined based on medical records and/or presence of smallpox vaccination characteristic scar. The most recent smallpox vaccination should have been received before 1980.
• Agree not to enroll in another study with an investigational medicinal product starting from Visit 0 and until the end of this study.
• Negative human immunodeficiency virus (HIV)-1 and HIV-2 antigen/antibody blood test result at Visit 0.
• Negative Hepatitis B surface antigen and negative core antibodies test results and negative anti Hepatitis C virus antibodies (anti-HCV), or negative Hepatitis C virus (HCV) polymerase chain reaction test result if the anti-HCV is positive at Visit 0.
• Volunteers of childbearing potential (VOCBP) must not be pregnant. VOCBP and men who are sexually active with partners of childbearing potential and their sexual partners born female should use a highly effective form of contraception from at least 28 days prior to Dose 1 up to at least 90 days after receiving the last dose of study treatment, and should agree not to donate eggs (ova, oocytes) or sperm.

You may not qualify if:

• History of mpox, smallpox or vaccinia infection based on volunteer-reported medical history.
• Pregnant, breastfeeding, planning pregnancy or planning to father children starting from Visit 0 and continuously until 90 days after receiving Dose 2.
• History of known or suspected severe adverse reaction including allergic reaction (e.g., anaphylaxis) to vaccines or to vaccine components such as lipids.
• Current or history of the following medical conditions at Visit 0 or Visit 1:
• Uncontrolled, moderate or severe asthma; asthma severity as defined in the US National Asthma Education and Prevention Program Expert Panel report
• Chronic obstructive pulmonary disease.
• Diabetes mellitus type 1 or type 2, including cases controlled with diet alone (Not excluded: history of isolated gestational diabetes).
• Hypertension: If a person has hypertension, exclude for blood pressure that is not well controlled. Well controlled blood pressure is defined as consistently ≤140 mm Hg systolic and ≤90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be \<150 mm Hg systolic and \<100 mm Hg.
• Systolic blood pressure ≥150 mm Hg or diastolic blood pressure ≥100 mm Hg.
• Malignancy, excluding localized basal or squamous cell cancer.
• Cardiovascular diseases, (e.g., myocarditis, pericarditis, coronary heart disease, myocardial infarction, congestive heart failure, cardiomyopathy or clinically significant arrhythmias, stroke or transient ischemic attack).
• Bleeding disorders (e.g., factor deficiency, coagulopathy, or platelet disorder).
• Seizure disorder: History of seizure(s) within past 3 years; use of medications in order to prevent or treat seizure(s) at any time within the past 3 years.
• Estimated glomerular filtration rate \<60 mL/min/1.73 m\^2.
• Chronic liver disease.

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (9)

California Research Foundation

San Diego, California, 92123, United States

Location

Alliance for Multispecialty Research, LLC

Kansas City, Missouri, 64114, United States

Location

Alliance for Multispecialty Research, LLC

Knoxville, Tennessee, 37909, United States

Location

University of Washington Virology Research Clinic

Seattle, Washington, 98104, United States

Location

Addenbrooke's Hospital - Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Royal Surrey County Hospital Foundation Trust, NIHR Royal Surrey Clinical Research Facility

Guildford, GU2 7XP, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust of St Thomas' Hospital

London, SE1 7EH, United Kingdom

Location

Medicine Evaluation Unit Ltd, The Langley Building, Wythenshawe Hospital

Manchester, M239QZ, United Kingdom

Location

University Hospital Southampton

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

• Zuiani A, Dulberger CL, De Silva NS, Marquette M, Lu YJ, Palowitch GM, Dokic A, Sanchez-Velazquez R, Schlatterer K, Sarkar S, Kar S, Chawla B, Galeev A, Lindemann C, Rothenberg DA, Diao H, Walls AC, Addona TA, Mensa F, Vogel AB, Stuart LM, van der Most R, Srouji JR, Tureci O, Gaynor RB, Sahin U, Poran A. A multivalent mRNA monkeypox virus vaccine (BNT166) protects mice and macaques from orthopoxvirus disease. Cell. 2024 Mar 14;187(6):1363-1373.e12. doi: 10.1016/j.cell.2024.01.017. Epub 2024 Feb 15.

  PMID: 38366591 DERIVED

MeSH Terms

Conditions

Mpox, Monkeypox

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Primate Diseases; Animal Diseases; Rodent Diseases

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2023
• First Posted: August 14, 2023
• Study Start: September 21, 2023
• Primary Completion: August 25, 2025
• Study Completion: March 4, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5); US (4)