A Phase III, Randomized, Double-Blind, Active-Controlled Non-Inferiority Trial Evaluating the Immunogenicity and Safety of Gardisun, a Quadrivalent Human Papillomavirus Vaccine, Compared with Gardasil® in Healthy Volunteers Aged 15-35 Years.

Background/Objectives: Human papillomavirus (HPV) infection is the leading cause of cervical cancer and is associated with several anogenital and oropharyngeal malignancies. Although licensed HPV vaccines are highly effective, access remains limited in many low- and middle-income countries due to cost, supply shortages, and implementation barriers. In this study, we evaluated the immunogenicity and safety of Gardisun, a newly developed quadrivalent prophylactic HPV vaccine, compared with Gardasil®. Methods: This Phase III randomized, double-blind, active-controlled, parallel-group non-inferiority trial enrolled 450 healthy participants stratified by sex and randomized (1:1) to receive three 0.5 mL intramuscular doses of Gardisun or Gardasil® on Days 0, 60, and 180. Participants were followed through to Day 210. The primary endpoint was the geometric mean titer (GMT) of antibodies against HPV types 6, 11, 16, and 18 one month after the administration of the third dose. Non-inferiority was defined as the lower bound of the 95% confidence interval (CI) for the GMT ratio exceeding 0.67. Safety was assessed through adverse event monitoring. Results: Of the 450 randomized participants, 422 completed the Month 7 visit and 429 received all three doses. Both vaccines induced antibody responses and seroconversion rates for all HPV types. The primary analysis met the non-inferiority criterion for HPV-6, while prespecified sensitivity analyses supported the existence of non-inferiority across all evaluated HPV types. Most adverse events were mild and transient, with no vaccine-related serious adverse events reported. Conclusions: Gardisun demonstrated robust immunogenicity and a safety profile comparable to that of Gardasil®, supporting its potential as an accessible alternative quadrivalent HPV vaccine for broader vaccination programs in resource-limited settings.