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

• ClinicalTrials.gov Identifier: NCT05432583
• Recruitment Status: Recruiting
• First Posted: June 27, 2022
• Last Update Posted: March 16, 2023
• Sponsor: BioNTech SE
• Information provided by (Responsible Party): BioNTech SE

Study Description

Brief Summary:

This exploratory trial will have two parts. While Part A will focus on the safety evaluations, 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 a BNT163 dose selected based on Part A data and enable a more comprehensive assessment of the impact of pre-existing immunity to Herpes Simplex Virus (HSV)-1 and -2 on the safety and BNT163-induced immune responses after one selected (higher) dose of BNT163 than could be done during the dose escalation performed in Part A.

Condition or disease	Intervention/treatment	Phase
Genital Herpes Simplex Type 2	Biological: BNT163; Other: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 108 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: observer-blinded trial
• Primary Purpose: Prevention
• Official Title: Phase I, Randomized, Observer-blinded, Placebo-controlled, 2-part, Dose Escalation and Expanded Safety Evaluation Trial to Evaluate the Safety, Tolerability, and Immunogenicity of an Investigational Prophylactic Vaccine for the Prevention of Genital Lesions Caused by Herpes Simplex Virus (HSV)-2 and Potentially HSV-1
• Actual Study Start Date: December 8, 2022
• Estimated Primary Completion Date: June 2025
• Estimated Study Completion Date: June 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: BNT163; Escalating dose levels	Biological: BNT163; Anti-viral ribonucleic acid (RNA) vaccine for active immunization against HSV-2 administered as intramuscular injection
Experimental: Placebo; Isotonic NaCl solution (0.9%)	Other: Placebo; Placebo

Outcome Measures

Primary Outcome Measures :

1. Frequency of solicited local reactions at the injection site (pain, erythema/redness, induration/swelling) recorded up to 7 days after each dose [ Time Frame: Up to 7 days after each dose ]
2. Frequency of solicited systemic reactions (vomiting, diarrhea, headache, fatigue/tiredness, myalgia, arthralgia, chills, and fever) recorded up to 7 days after each dose [ Time Frame: Up to 7 days after each dose ]
3. Percentage of participants with at least one unsolicited adverse event (AE) occurring up to 28 days after each dose [ Time Frame: From Day 1 up to Day 197 ]
4. Percentage of participants in each cohort with at least one serious adverse event, or adverse event of special interest, or medically attended adverse event occurring up to 24 weeks post-Dose 3 [ Time Frame: From Day 1 up to Day 337 ]
5. Frequency of unsolicited AEs occurring up to 28 days after each dose [ Time Frame: From Day 1 up to Day 197 ]
6. Percentage of unsolicited AEs occurring up to 28 days after each dose [ Time Frame: From Day 1 up to Day 197 ]

Secondary Outcome Measures :

1. Geometric mean titer (GMT) at each time point [ Time Frame: From Day 1 up to Day 337 ]
   HSV-2 glycoproteins (g)C2, gD2, and gE2 binding antibody titers enzyme-linked immunosorbent assay (ELISA). HSV-2 neutralizing antibody titers.
2. Geometric mean fold (GMF) change from baseline of neutralizing and binding antibody titers to each time point after vaccination [ Time Frame: From Day 1 up to Day 337 ]
   HSV-2 gC2, gD2, and gE2 binding antibody titers (ELISA). HSV-2 neutralizing antibody titers.
3. 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 [ Time Frame: From Day 1 up to Day 337 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• 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, lifestyle restrictions (e.g., to practice social distancing and to follow good practices to reduce their chances of being infected or spreading COVID-19), 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.
• Negative HIV-1 and HIV-2 blood test at Visit 0.
• Negative Hepatitis B surface antigen at Visit 0.
• Negative anti-Hepatitis C virus antibodies (anti-HCV), or undetectable hepatitis C virus (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 will not be considered VOBCP.
• VOCBP who agree to practice a highly effective form of contraception and to require their male partners to use condoms with a spermicidal agent, starting at Visit 0 and continuously until 60 days after receiving the last trial treatment.
• VOCBP who agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during trial, starting at Visit 0 and continuously until 60 days after receiving the last trial treatment.
• Men who are sexually active with a VOCBP and have not had a vasectomy who agree to use condoms with a spermicidal agent and to practice a highly effective form of contraception with their partners of childbearing potential during the trial, starting at Visit 0 and continuously until 90 days after receiving the last trial treatment.
• Men who are willing to refrain from sperm donation, starting at Visit 0 and continuously until 90 days after receiving the last trial treatment.

Exclusion Criteria:

• 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.
• 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 at 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:

  • Primary immunodeficiencies.
  • History of solid organ or bone marrow transplantation.
  • Asplenia: any condition resulting in the absence of a functional spleen.
  • Currently existing or history of autoimmune disease including and not limited to thyroid autoimmune disease, multiple sclerosis, psoriasis, etc.
• Use of any non-trial IMP within 28 days before Dose 1 in this trial (Visit 1) or planned receipt continuously until Visit 12 in this trial, or participation in the active treatment phase of another interventional clinical trial.
• Previous vaccination with an investigational herpes virus vaccine at any time.

• Any non-trial vaccination within 28 days before Dose 1 and continuously until 28 days after receiving Dose 3.

  o Note: Licensed inactivated and mRNA vaccines (e.g., seasonal influenza and COVID-19 vaccines) are allowed to be given at least 14 days before or 14 days after each IMP administration. Licensed live attenuated vaccines (e.g., influenza vaccines) are allowed at least 28 days before or 28 days after any IMP administration.

• Received allergy treatment with antigen injections within 28 days before first IMP administration or that are scheduled within 14 days after Visit 1.
• Received blood/plasma products or immunoglobulin within 120 days before Visit 1 or planned administration starting at Visit 0 until completion of Visit 12.
• Received chronic suppressive antiviral therapy for treatment of recurrent HSV-1 and/or HSV-2 genital herpes infections (i.e., oral acyclovir, oral valacyclovir, oral famciclovir, and/or intravenous ganciclovir) from 1 year prior to Visit 0 until completion of Visit 12.
• Any existing condition which may affect vaccine injection and/or assessment of local reactions assessment at the injection site, e.g., tattoos, severe scars, etc.
• Vulnerable individuals as per International Council for Harmonisation (of Technical Requirements for Pharmaceuticals for Human Use) (ICH) E6 definition, i.e., are individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.

• Any screening hematology and/or blood chemistry laboratory value that meets the definition of a Grade ≥1 abnormality at Visit 0.

  o Note: With the exception of direct bilirubin, participants with any stable Grade 1 abnormalities (according to the toxicity grading scale) may be considered eligible at the discretion of the investigator.

• Part B only: HSV serology at Visit 0 is HSV-1 positive/HSV-2 negative, HSV-1 negative/HSV-2 positive, or HSV-1 positive/HSV-2 positive and Part B randomization cap (i.e., 36 combining HSV-1 positive/HSV-2 negative, HSV-1 negative/HSV-2 positive, and HSV-1 positive/HSV-2 positive participants) has already been reached.

Contacts and Locations

Contacts

Contact: BioNTech clinical trials patient information; +49 6131 9084 ext 0; patients@biontech.de

Locations

United States, North Carolina

Accellacare Raleigh Medical Group; Recruiting

Raleigh, North Carolina, United States, 27609

Accellacare PMG Research Wilmington LLC; Recruiting

Wilmington, North Carolina, United States, 28401

Sponsors and Collaborators

BioNTech SE

Investigators

• Study Director: BioNTech Responsible Person; BioNTech SE

More Information

• Responsible Party: BioNTech SE
• ClinicalTrials.gov Identifier: NCT05432583
• Other Study ID Numbers: BNT163-01
• First Posted: June 27, 2022
• Last Update Posted: March 16, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by BioNTech SE:

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; RNA Vaccine; Vaccine

Additional relevant MeSH terms:

Herpes Simplex; Herpes Genitalis; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Skin Diseases, Viral; Skin Diseases, Infectious; Skin Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases