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

NCT05988203 | Completed Phase 1 Results FDA Drug

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

Brief Summary

This was 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 was originally planned to include four substudies, i.e., substudy A (SSA), substudy B (SSB), substudy C (SSC), and substudy D (SSD). Sponsor decided not to conduct SSC, thus three substudies (SSA, SSB, and SSD) were conducted. In SSA and SSB, dosing started with an initial sentinel group, followed by the expansion cohort. In SSD, dosing was initiated after the interim analysis of SSA and SSB 1-month post-Dose 2 safety, reactogenicity, and immunogenicity data was received. 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 (5)

• Number of Participants Reporting Solicited Local Reactions At the Injection Site

  All reactogenicity events information recorded via the participant e-diaries or solicited by the investigator were considered as solicited events. Solicited local reactions were: pain at the injection site, erythema/redness, and induration/swelling. Any local reaction indicates participants with any reactions, including reactions that do not qualify for Grade 1 (\<2.5 cm for erythema/redness or induration/swelling). The intensity of local reaction was assessed by the participant and may be confirmed or corrected by the investigator; grades were defined as Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially life-threatening.

  Up to 7 days post any vaccination, and up to 7 days post each vaccination dose (that is, post-dose 1 [up to Day 8]) and post-dose 2 [up to Day 38])

• Number of Participants Reporting Solicited Systemic Events

  All reactogenicity events information recorded via the participant e-diaries or solicited by the investigator were considered as solicited events. Solicited systemic reactions were: fever, chills, fatigue/tiredness, headache, muscle pain/myalgia, joint pain/arthralgia, vomiting, and diarrhea. Any systemic reaction indicated participants with any Grade \>=1 reactions. The intensity of systemic events was assessed by the participants and may be confirmed or corrected by the investigator; grades were defined as Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially life-threatening.

  Up to 7 days post any vaccination, and up to 7 days post each vaccination dose (that is, post Dose 1 [up to Day 8] and post Dose 2 [up to Day 38])

• Number of Participants With At Least One Unsolicited Adverse Event (AE)

  An AE was defined as any untoward medical occurrence in a participant administered with a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment. All AE information or safety data including solicited events persisting beyond 7 days that were voluntarily communicated by the participant or collected by the investigator (that is, ECG or laboratory results etc.) were considered unsolicited events. The intensity of AEs was graded by the investigator. Grades were defined as: Grade 1 - Mild; does not interfere with the trial participant's usual function; Grade 2 - Moderate; interferes to some extent with the trial participant's usual function Grade 3 - Severe; interferes significantly with the trial participant's usual function; and Grade 4 - Potentially life-threatening; life-threatening consequences, urgent intervention required.

  Up to 28 days post any vaccination, and up to 28 days post each vaccination dose (that is, post-dose 1 [up to Day 29] and post-Dose 2 [up to Day 59])

• Number of Participants With At Least One Serious Adverse Event (SAE)

  An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death and was life-threatening. It also included any event requiring hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, caused a congenital anomaly or birth defect, or any other event determined as SAE as per medical or scientific judgment.

  From Dose 1 up to Day 201

• Number of Participants With At Least One Adverse Event of Special Interest (AESI)

  An AESI, serious or non-serious, was one of scientific and medical concern specific to the sponsor's product or program, for which monitoring and rapid communication by the investigator to the sponsor was appropriate.

  From Dose 1 up to Day 201

Study Arms (5)

BNT166a SSA: 10 mcg

EXPERIMENTAL

Participants received two intramuscular doses of the multivalent RNA-based vaccine BNT166a at Visit 1 (Day 1) and at Visit 5 (Day 31) for active immunization against monkeypox.

Biological: BNT166a

SSA: BNT166a 30 mcg

EXPERIMENTAL

Participants received two intramuscular doses of the multivalent RNA-based vaccine BNT166a at Visit 1 (Day 1) and at Visit 5 (Day 31) for active immunization against monkeypox.

Biological: BNT166a

SSA: BNT166a 60 mcg

EXPERIMENTAL

Participants received two intramuscular doses of the multivalent RNA-based vaccine BNT166a at Visit 1 (Day 1) and at Visit 5 (Day 31) for active immunization against monkeypox.

Biological: BNT166a

SSB: BNT166a 30 mcg

EXPERIMENTAL

Participants received two intramuscular doses of the multivalent RNA-based vaccine BNT166a at Visit 1 (Day 1) and at Visit 5 (Day 31) for active immunization against monkeypox.

Biological: BNT166a

SSD: BNT166a 60 mcg

EXPERIMENTAL

Participants received two intramuscular doses of the multivalent RNA-based vaccine BNT166a at Visit 1 (Day 1) and at Visit 6 (Day 31) for active immunization against monkeypox.

Biological: BNT166a

Interventions

BNT166a BIOLOGICAL

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

BNT166a SSA: 10 mcg; SSA: BNT166a 30 mcg; SSA: BNT166a 60 mcg; SSB: BNT166a 30 mcg; SSD: BNT166a 60 mcg

Eligibility Criteria

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

You may qualify if:

• Had given informed consent by signing and dating the informed consent form (ICF) before initiation of any study-specific procedures.
• Were willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study, including the prohibited concomitant medications. This included that they were able to understand and follow study-related instructions.
• SSA and SSD only: Were 18 through 45 years of age (inclusive) at the time of informed consent.
• SSB only: Were 50 through 65 years of age (inclusive) at the time of informed consent.
• Had a body mass index over 18.5 kg/m\^2 and under 30 kg/m\^2 and weighed at least 50 kg at Visit 0.
• Were 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: Had no prior history of known or suspected smallpox vaccination and no detectable smallpox vaccination characteristic scar (vaccinia-naïve participants).
• SSB only: Had 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 was received before 1980.
• Agreed 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 was positive at Visit 0.
• Volunteers of childbearing potential (VOCBP) must not have been pregnant. VOCBP and men who were sexually active with partners of childbearing potential and their sexual partners born female should have used 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 have agreed 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, were planning pregnancy or were 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 had hypertension, excluded for blood pressure that was not well controlled. Well controlled blood pressure was 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 have been \<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; used 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 (2)

• Bahner F, Faust SN, Davies LRL, Blokhina O, Brandon DM, Smith WB, Chatterjee VKK, Hassanin H, Babu TM, Zuiani A, Steinhauser S, Poran A, Brittain C, Mucker E, Hooper JW, van der Most RG, Alonso PL, Tureci O, Mensa FJ, Sahin U. Safety and immunogenicity of mRNA-based mpox vaccine candidate BNT166a: an open-label, dose-escalation, first-in-human trial. Lancet Infect Dis. 2026 Jun 3:S1473-3099(26)00177-5. doi: 10.1016/S1473-3099(26)00177-5. Online ahead of print.

  PMID: 42235570 RESULT

• 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

Results Point of Contact

• Title: BioNTech clinical trials patient information
• Organization: BioNTech SE

patients@biontech.de

61319084

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: September 15, 2026
• Results First Posted: September 15, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5); US (4)