Safety of a quadrivalent human papillomavirus vaccine in a Phase 3, randomized, double-blind, placebo-controlled clinical trial among Chinese women during 90 months of follow-up

Background: A quadrivalent human papillomavirus (qHPV) vaccine (HPV6/11/16/18) has demonstrated efficacy and acceptable safety in international studies. However, these studies did not include participants from mainland China, which has a substantial burden of HPV-related disease. This is the first safety report with a follow-up period of up to 90 months from a randomized, double-blind, placebo-controlled trial of qHPV vaccine in Chinese women 20-45 years of age. Methods: Participants were randomized 1:1 to receive three doses of qHPV vaccine or placebo (Day 1, Month 2, and Month 6). Efficacy outcomes are reported elsewhere. Injection-site and systemic adverse events (AEs) were collected using vaccination report cards (VRCs) for 15 days following each vaccination. Serious AEs (SAES), pregnancy outcomes, new medical conditions, and fetal/infant SAES were collected during the entire study. Results: Of 3006 participants randomized, AEs were reported by 926 (61.8%) qHPV vaccine recipients and 856 (57.1%) placebo recipients over the entire study. Four participants (two in each group) discontinued the study vaccination due to AEs that were considered vaccination-related. Within 15 days following any vaccination, injection-site AEs prompted for on the VRC were more frequent among qHPV vaccine recipients (37.6% vs 27.8%), and systemic AEs prompted for on the VRC were similar in frequency between qHPV vaccine and placebo groups (46.8% vs 45.1%). Thirty-eight and 43 participants reported SAES in qHPV vaccine and placebo groups, respectively. No SAE was considered qHPV vaccine-related. Pregnancy outcomes, fetal/infant SAES, and new medical conditions were generally similar in frequency between the qHPV vaccine and placebo groups, and within normal ranges. Conclusion: The qHPV vaccine was well tolerated and demonstrated a favorable safety profile in Chinese women 20-45 years of age, consistent with findings from global trials and safety surveillance studies. (C) 2018 Published by Elsevier Ltd.