A Clinical Trial in Healthy Volunteers and Volunteers With Recurrent Genital Herpes to Study the Safety, Tolerability, and Immune Responses After Vaccination With an Investigational Vaccine Designed to Prevent Genital Herpes Lesions

NCT05432583 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: BNT163-01
• Study Type: interventional
• Target: 318
• Locations: 1 country
• Sites: 6

Brief Summary

This exploratory trial will have three parts. Part A is a dose escalation part, Part B is an expanded safety and dose evaluation part, and Part C is a safety and immunogenicity evaluation part in individuals with recurrent HSV-2 genital herpes. Part A will focus on the safety evaluations, and in addition, vaccine-induced immune responses (specifically neutralizing antibodies) will also be analyzed to assess if there is a dose-response. Part B of the trial will expand the safety characterization for two dose levels of BNT163 selected based on Part A data and will also enable a more comprehensive assessment of the impact of pre-existing immunity to HSV-1 and -2 on the safety and immune responses to BNT163. Part C will evaluate safety and immunogenicity of BNT163 compared to a placebo in a three-dose regimen in participants with a history of HSV-2 recurrent genital herpes.

Conditions

Genital Herpes Simplex Type 2

Keywords

Prevention of genital lesions caused by herpes simplex virus-2; Prevention of genital lesions caused by herpes simplex virus-1; Genital infection caused by HSV; Recurrent herpes simplex virus-2 genital herpes; RNA Vaccine; Vaccine

Outcome Measures

Primary Outcomes (6)

• Frequency of solicited local reactions at the injection site (pain, erythema/redness, induration/swelling) recorded up to 7 days after each dose

  For each dose level (DL) per BNT163 dosing schedule and for the combined placebo group.

  Up to 7 days after each dose

• Frequency of solicited systemic reactions (vomiting, diarrhea, headache, fatigue/tiredness, myalgia, arthralgia, chills, and fever) recorded up to 7 days after each dose

  For each DL per BNT163 dosing schedule and for the combined placebo group.

  Up to 7 days after each dose

• Percentage of participants with at least one unsolicited adverse event (AE) occurring up to 28 days after each dose

  For each DL per BNT163 dosing schedule and for the combined placebo group.

  From Day 1 up to Day 197

• Percentage of participants in each cohort with at least one serious AE, or AE of special interest, or medically attended AE occurring up to 24 weeks post-Dose 3 (Parts A & B) or post-Dose 2 (Part C)

  For each DL per BNT163 dosing schedule and for the combined placebo group.

  From Day 1 up to Day 337

• Number of unsolicited AEs occurring up to 28 days after each dose

  For each DL per BNT163 dosing schedule and for the combined placebo group.

  From Day 1 up to Day 197

• Percentage of unsolicited AEs occurring up to 28 days after each dose

  For each DL per BNT163 dosing schedule and for the combined placebo group.

  From Day 1 up to Day 197

Secondary Outcomes (3)

• Geometric mean titer (GMT) at each time point

  From Day 1 up to Day 337

• Geometric mean fold (GMF) change from baseline of neutralizing and binding antibody titers to each time point after vaccination

  From Day 1 up to Day 337

• Part A and B only - Percentage of participants with seroconversion defined as a minimum of 4-fold increase from baseline of neutralizing and binding antibody titers to each subsequent time point after vaccination

  From Day 1 up to Day 337

Study Arms (6)

Part A - BNT163

EXPERIMENTAL

Escalating dose levels

Biological: BNT163

Part A - Placebo

PLACEBO COMPARATOR

Isotonic NaCl solution (0.9%)

Other: Placebo

Part B - BNT163 Dose 1

EXPERIMENTAL

Biological: BNT163

Part B - BNT163 Dose 2

EXPERIMENTAL

Biological: BNT163

Part C - BNT163

EXPERIMENTAL

One fix dose level of BNT163

Biological: BNT163

Part C - Placebo

PLACEBO COMPARATOR

Isotonic NaCl solution (0.9%)

Other: Placebo

Interventions

BNT163 BIOLOGICAL

Anti-viral ribonucleic acid (RNA) vaccine for active immunization against HSV-2 administered as intramuscular injection

Part A - BNT163; Part B - BNT163 Dose 1; Part B - BNT163 Dose 2; Part C - BNT163

Placebo OTHER

Placebo

Part A - Placebo; Part C - Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Have given informed consent by signing and dating the informed consent form (ICF) before initiation of any trial-specific procedures.
• Are aged 18 to 55 years, have a body mass index over 18.5 kg/m\^2 and under 35 kg/m\^2 and weigh at least 50 kg at Visit 0.
• Are willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the trial. This includes that they are able to understand and follow trial-related instructions.
• Are overall healthy in the clinical judgment of the investigator based on medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs, and screening laboratory tests (blood clinical laboratory) at Visit 0 (for Part C only: (all results must be available prior to Pre-dose Visit 1).
• Part C only: Have had
• a diagnosis (\>1 year) of genital herpes confirmed in medical records; and
• with at least 3 and no more than 9 participant-reported genital herpes recurrences either in the 1 year preceding Visit 0, or, if currently on continuous antiviral therapy, in the 1 year preceding the start of continuous antiviral therapy.
• Part C only: Are seropositive for HSV-2 as determined by Western Blot (result must be available prior to Pre-Dose Visit 2).
• Part C only: Are willing to comply with the protocol-specified schedule for continuous antiviral therapy.
• Part C only: Are willing to refrain from the use of episodic antiviral therapy according to the antiviral therapy schedule. Episodic antiviral therapy may be used outside the prohibited periods.
• Negative human immunodeficiency virus (HIV)-1 and HIV-2 blood test at Visit 0.
• Negative Hepatitis B surface antigen at Visit 0.
• Negative anti-Hepatitis C virus (HCV) antibodies (anti-HCV), or undetectable HCV viral load if the anti-HCV is positive at Visit 0.
• Negative syphilis test at Visit 0.
• Volunteers of childbearing potential (VOCBP): negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test at Visit 0 and negative urine pregnancy test prior to each investigational medicinal product (IMP) administration and at the end of the trial. Volunteers born female that are postmenopausal (verified by follicle stimulating hormone \[FSH\] level) or permanently sterilized (verified by medical records) will not be considered VOBCP.

You may not qualify if:

• Breastfeeding or intending to become pregnant within the projected duration of the trial starting with Visit 0 until 60 days after receiving the last trial treatment or intending to father children within the projected duration of the trial starting with Visit 0 until 90 days after receiving the last trial treatment.
• Part A \& B only: Current or history of symptomatic genital herpes infections. Volunteers with oral herpes or herpetic whitlow will not be excluded.
• Current or history of any form of ocular HSV infection or HSV-related central nervous system disease or complication.
• History of any serious adverse reactions to vaccines or to vaccine components such as lipids, and including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.
• Current or history of the following medical conditions:
• Uncontrolled or moderate or severe respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease); symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention Program Expert Panel report;
• History of thyroidectomy, or thyroid disease requiring medication during the last 12 months;
• History of diabetes mellitus type 1 or type 2, including cases controlled with diet alone (not excluded: history of isolated gestational diabetes);
• Hypertension (elevated blood pressure or hypertension during screening or previously that is not well controlled only \[consistently ≤140 mm Hg systolic and ≤90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤150 mm Hg systolic and ≤90 mm Hg diastolic at enrollment\] or if systolic blood pressure ≥150 mm Hg at enrollment or diastolic blood pressure ≥100 mm Hg confirmed by two measurements prior to enrollment);
• Malignancy within 5 years of Visit 0, excluding localized basal or squamous cell cancer;
• Current or history of cardiovascular diseases, e.g., myocardial infarction, congestive heart failure, cardiomyopathy, or clinically significant arrhythmias, myocarditis, or pericarditis;
• Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions);
• Seizure disorder: History of seizure(s) within past 3 years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
• History of psychiatric illness, including alcohol abuse or drug addiction within 1 year before Visit 0, or a history (within the past 5 years) of substance abuse or known medical, psychological, or social conditions which, in the opinion of the investigator, could compromise their wellbeing if they participate as participants in the trial, or that could prevent, limit, or confound the protocol specified assessments.
• Any of the following associated with immune dysregulation:

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (6)

Alliance for Multispecialty Research, LLC

Tempe, Arizona, 85281, United States

Location

Great Lakes Clinical Trials - Flourish Research

Chicago, Illinois, 60640, United States

Location

Accellacare Raleigh Medical Group

Raleigh, North Carolina, 27609, United States

Location

Accellacare PMG Research Wilmington LLC

Wilmington, North Carolina, 28401, United States

Location

CTI Clinical Research Center

Cincinnati, Ohio, 45212, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: observer-blinded trial
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2022
• First Posted: June 27, 2022
• Study Start: December 8, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)