Long-term Follow-up of Bivalent Human Papillomavirus (HPV) Vaccine Study in Women

A Multicenter, Open-label, Long-term Extension Study to Evaluate the Long-term Protective Efficacy and Immunogenic Persistence of the Bivalent Human Papillomavirus Vaccine (Pichia Pastoris) Administered to Healthy Females Aged 18-30 During the 311-HPV-1003 Study

This extension study aims to evaluate the long-term protection and immune response of the bivalent HPV vaccine in women aged 18-30 who participated in a previous efficacy study (311-HPV-1003). Participants will be monitored over two years, with two visits at 96 and 120 months after their initial vaccination. No additional vaccine doses will be given. Cervical samples will be obtained for ThinPrep Cytologic Testing (TCT) and HPV DNA typing. If applicable, participants meeting referral criteria for colposcopy will undergo the procedure during these visits, and tissue samples will be collected from those requiring a biopsy. Blood samples will be drawn from an immunology subset for antibody testing.The study includes data collection from multiple sites across China to assess the vaccine's long-term efficacy in preventing HPV-related cervical diseases and its durability over time.

Study Overview

• Status: Active, not recruiting
• Conditions: Cervical Cancer; Vulvar Cancer; Vaginal Cancer; Human Papillomavirus Infection; CIN - Cervical Intraepithelial Neoplasia
• Intervention / Treatment: Biological: HPV-16/18 vaccine; Biological: Placebo

• Study Type: Observational
• Enrollment (Actual): 5372

Contacts and Locations

Study Locations

• China
  • Guangxi
    • Lingchuan, Guangxi, China
      • Lingchuan Center for Disease Control and Prevention
    • Quanzhou, Guangxi, China
      • Quanzhou Center for Disease Control and Prevention
    • Xing'an, Guangxi, China
      • Xing'an Center for Disease Control and Prevention
  • Hebei
    • Daming, Hebei, China
      • Daming Center for Disease Control and Prevention
    • Dingxing, Hebei, China
      • Dingxing Center for Disease Control and Prevention
    • Zhengding, Hebei, China
      • Zhengding Center for Disease Control and Prevention
  • Henan
    • Puyang, Henan, China
      • Puyang Center for Disease Control and Prevention
    • Wenxian, Henan, China
      • Wenxian Center for Disease Control and Prevention
  • Shanxi
    • Xiangfen, Shanxi, China
      • Xiangfen County People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Participants in this long-term follow-up study were originally enrolled in the 311-HPV-1003 study and are drawn from multiple clinical sites across four provinces in China, including Guangxi, Hebei, Henan, and Shanxi. These participants represent a community-based sample of healthy women who received at least one dose of the Bivalent HPV vaccine or Placebo during the original study.

Description

Inclusion Criteria:

• Have the ability to understand and provide informed consent by signing the informed consent form (non-illiterate).
• Have the ability to comply with protocol requirements, such as attending scheduled visits and responding to follow-up phone calls.
• Prior enrollment in the 311-HPV-1003 study, with at least one dose of the study vaccine administered.
• At least one documented gynecological visit between 6 and 48 months during the previous 311-HPV-1003 study.
• Refrain from vaginal intercourse for 48 hours and avoid behaviors such as vaginal douching or using vaginal medications that could interfere with gynecological examinations or sample collection for 72 hours prior to each gynecological visit.

Exclusion Criteria:

• Participants who received another HPV vaccine during the prior 311-HPV-1003 study or between the end of that study and enrollment in this extension study.
• Participants diagnosed with HPV 16- or 18-related CIN2+ by an independent pathology expert panel during the prior 311-HPV-1003 study, or who were definitively diagnosed with HPV 16- or 18-related CIN2+ through external testing after the prior study ended.
• Participants who, at baseline in the 311-HPV-1003 study, tested positive for both HPV 16 and 18 antibodies, or were positive for both HPV 16 and 18 (by Cobas 4800), or whose cytology was not normal or of low-grade changes.
• Participants who are pregnant at the time of gynecological visits or within three months prior to the visit.
• Participants with any other factors deemed unsuitable for participation in the clinical trial, as determined by the investigator.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HPV-2 vaccine group; Participants received the bivalent HPV vaccine (0.5 mL in a 3-dose regimen) in the base study (NCT02733068). No study vaccination will be administered in long-term follow-up study .	Biological: HPV-16/18 vaccine; Recombinant human papillomavirus virus-like particle vaccine (Type 16 and 18 L1 Proteins, Yeast)
Placebo group; Participants received the placebo (0.5 mL in a 3-dose regimen) in the base study (NCT02733068). No study vaccination will be administered in long-term follow-up study .	Biological: Placebo; Placebo containing the same formulation as the active vaccine (Type 16 and 18 L1 proteins, Yeast) but without the active substance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cumulative Protective Efficacy Against HPV-16 and/or HPV-18-Related Cervical Intraepithelial Neoplasia (CIN) Grade 2 or Higher (CIN2+), Adenocarcinoma In Situ (AIS), and Cervical Cancer	Up to 96 months and 120 months after initial vaccination in base study.

Secondary Outcome Measures

Outcome Measure	Time Frame
Cumulative protective efficacy against cytological HPV-16 and/or HPV-18 infection	Up to 96 months and 120 months after initial vaccination in base study.
Cumulative protective efficacy against HPV-16 and/or HPV-18-related CIN1+	Up to 96 months and 120 months after initial vaccination in base study.
HPV 16/18 neutralizing antibody GMT and seropositivity rates	At 96 months and 120 months after initial vaccination in base study.

Collaborators and Investigators

• Sponsor: Shanghai Zerun Biotechnology Co.,Ltd
• Collaborators: Yuxi Zerun Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: January 10, 2025
• First Submitted That Met QC Criteria: January 10, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 10, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Bivalent HPV vaccine; Long-term protective efficacy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Infections; Virus Diseases; Uterine Diseases; Genital Diseases, Female; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Genital Neoplasms, Female; Precancerous Conditions; Uterine Cervical Diseases; Tumor Virus Infections; Vulvar Diseases; Vaginal Diseases; Papillomavirus Infections; Vulvar Neoplasms; Uterine Cervical Dysplasia; Vaginal Neoplasms
• Other Study ID Numbers: 311-HPV-1003-EXTEND (Other Identifier: Shanghai Zerun Biotech)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No