Phase I, Randomized, Observer-blinded, 3-part, Dose Escalation and Expanded Safety and Dose 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
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 subjects with a history of HSV-2 recurrent genital herpes.
• 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 HSV-2 genital herpes confirmed in medical records 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 suppressive therapy, in the 1 year preceding the start of suppressive therapy.
⁃ Are seropositive for HSV-2 as determined by Western Blot (result must be available prior to Dose 1).
⁃ Are willing to comply with the protocol-specified antiviral suppression therapy schedule.
⁃ Are willing to refrain from the use of episodic antiviral therapy during the two 28-day anogenital swabbing periods. Episodic therapy may be used outside the swabbing 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.
• VOCBP who agree to practice a highly effective form of contraception and to require their male partners to use condoms coated 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 coated 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.