Efficacy, immunogenicity, and safety of the 9-valent human papillomavirus vaccine in males aged 16-26 years in Japan: a randomised, double-blind, placebo-controlled trial.
TL;DR
The 9vHPV vaccine prevents anogenital persistent infection related to vaccine-targeted HPV types in males and has an acceptable safety profile, which support the use of the 9vHPV vaccine in males to prevent HPV-related anogenital diseases.
Abstract
Background
Efficacy of the nine-valent human papillomavirus (9vHPV; HPV6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine was shown in females and inferred for males through immunobridging. We evaluated the efficacy of the 9vHPV vaccine in males aged 16-26 years.
Methods
This randomised, double-blind, placebo-controlled, efficacy, immunogenicity, and safety phase 3 trial was conducted at 22 clinical research, hospital, medical, or treatment sites in Japan, with masking of investigators, sponsor personnel, and participants. Healthy males aged 16-26 years with no history of human papillomavirus (HPV)-related lesions and no previous HPV vaccination were randomly assigned (1:1) centrally, using permutated blocks (block sizes of four), to receive three intramuscular injections of the 9vHPV vaccine or placebo (saline) at day 1, month 2, and month 6. The primary and secondary efficacy endpoints were the combined incidences of 6-month anogenital persistent infection related to HPV6, 11, 16, and 18 and HPV31, 33, 45, 52, and 58. Anogenital swabs and external genital tissue samples were tested for the presence of HPV DNA. Tissue samples were adjudicated for histopathology diagnosis. The primary and secondary efficacy evaluations were tested for superiority with a margin of 0% in the per-protocol population. Another secondary endpoint was antibody responses to each vaccine-targeted HPV type at month 7; immunogenicity analyses were conducted in the per-protocol immunogenicity population. Safety was assessed in participants who received at least one dose of vaccine or placebo. This study is registered with ClinicalTrials.gov (NCT04635423) and is completed.
Findings
Between Nov 30, 2020, and Dec 25, 2021, 1059 participants were enrolled and randomly assigned to receive the 9vHPV vaccine (n=529) or placebo (n=530). Vaccine efficacy for the primary and secondary endpoints was 89·3% (95% CI 55·4-98·2; p=0·0002) and 63·5% (2·7-86·0; p=0·023), respectively, in the initial efficacy analysis based on a visit cutoff date of Dec 29, 2023, and 91·6% (67·7-98·6) and 72·9% (38·7-89·3) in the end-of-study efficacy analysis based on a visit cutoff date of July 16, 2024. Seroconversion rates were greater than 98% for each vaccine-targeted HPV type. Injection-site adverse events were reported in 370 (70%) of 529 9vHPV vaccine recipients and 162 (31%) of 530 placebo recipients, and vaccine-related systemic adverse events in 58 (11%) vaccine recipients and 52 (10%) placebo recipients; most cases were mild or moderate. No deaths, vaccine-related serious adverse events, or discontinuations due to adverse events were reported.
Interpretation
The 9vHPV vaccine prevents anogenital persistent infection related to vaccine-targeted HPV types in males and has an acceptable safety profile. These findings support the use of the 9vHPV vaccine in males to prevent HPV-related anogenital diseases.
Funding
Merck Sharp & Dohme. TRANSLATIONS For the Japanese translation of the abstract see Supplementary Material section.