Immunobridging Study of 9-valent Human Papillomavirus Recombinant Vaccine in Chinese Females Aged 9 to 19 Years

Evaluating the Immunogenicity and Safety of 9-valent Human Papillomavirus(Type6, 11, 16, 18, 31, 33, 45, 52 and 58) Recombinant Vaccine in Chinese Females Aged 9 to 45 Years: A Phase 3, Open-label, Non-randomised Clinical Trial

This phase 3 study will evaluate the immunogenicity and safety of 9-valent HPV recombinant vaccine in Chinese females aged 9 to 45 years

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer; Vulvar Cancer; Vaginal Cancer; CIN1; CIN2; VaIN1; VaIN2; VaIN3; Genital Wart; VIN 1; VIN 2; VIN 3; AIS; HPV Infections; CIN 3
• Intervention / Treatment: Biological: 9-valent HPV vaccine

Detailed Description

This study (protocol 9-HPV-3003) is an immunogenicity and safety study in the subjects (9-19 years of age) who received the 9-valent HPV recombinant vaccine compared with the subjects (20-45 years of age). In this study, we will assess whether the immunogenicity of the 9-valent HPV vaccine given 3-dose schedule in the subjects (9-19 years of age) in noninferior to that in the subjects (20-45 years of age) receiving 3 doses, while assessing the safety of this vaccine.

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Huakun Lv; Phone Number: 13588458021; Email: hklv@cdc.zj.cn

Study Locations

• China
  • Hangzhou, China
    • Recruiting
    • Huakun Lv
    • Contact: Huakun Lv; Phone Number: 13588458021; Email: hklv@cdc.zj.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Inclusion Criteria for the first stage:

1. Healthy Chinese females aged 9 to 45 years; Provide legal identification;
2. The subject voluntarily agrees to enroll in this study. If the subject is a minor, both the subject and subject's legal guardian should voluntarily agree to enroll in this study and sign an informed consent form;
3. Be able to understand the study procedures and promise to participate in regular follow-ups under the requirements;
4. Had a negative urine pregnancy test on the day of enrollment, among the subjects of childbearing age; Not in the duration of breast-feeding and no birth plan within 7 months; According to the investigator's judgment that there is no possibility of pregnancy at that time: subjects have taken effective contraception, or asexual life after the last menstrual period, or use IUD, or had undergone ligation; subjects agree to continue take effective contraception such as taking OCS and condom use;

5. No fever symptoms on the day of enrollment (aged> 14 years old, axillary temperature<37.3°C; aged ≤ 14 years old, axillary temperature<37.5°C );

   Inclusion Criteria for the second stage:

6. Received all 3 doses of trial vaccination;
7. Subjects aged 9 to 19 years at the first stage.

Exclusion Criteria:

1. Received marketed HPV vaccine or plan to receive marketed HPV vaccine during this study period or have enrolled in HPV vaccine clinical trials;
2. History of positive test to HPV, history of cervical cancer (e.g. abnormal screening test results, abnormal cervical biopsy results, including CIN, AIS, and cervical cancer) or history of hysterectomy (vaginal or abdominal radical hysterectomy), or history of pelvic radiotherapy; History of genital diseases related to HPV infection (e.g. uterine peristalsis, VIN, VAIN, AIN, and related cancers); History of STDs, including syphilis, gonorrhea, genital herpes, Mycoplasma genitalium, Lymphgranuloma Venereum, granuloma inguinale, etc.;
3. Known allergy to any vaccine components or history of severe allergic diseases requiring treatment, including shock, laryngeal edema, urticarial, Henoch-Schonlein purpura, Arthus reaction, etc.;
4. Had primary or acquired immunodeficiency such as HIV, SLE, JRA, etc. or received immunosuppressive treatment within one month before study such as long-term glucocorticoid use(≥2mg per kg per day, lasted more than two wks), or plan to receive such treatment from day 0 to month 7 after the last dose;
5. Had chronic diseases or congenital malformations, which might interfere with the process and completion of this study, such as Down Syndrome, heart diseases, liver diseases, chronic diabetes complications, and malignant tumor;
6. Enrolling or plan to enroll in other clinical trials (drug or vaccine);
7. Had infectious diseases such as TB, viral hepatitis, and/or HIV infection;
8. Had convulsions, epilepsy, encephalopathy, and mental illness or family history;
9. With prohibitive contraindications such as Thrombocytopenia or coagulopathy;
10. Asplenic, functionally asplenic, or splenectomy caused by any condition;
11. Within 3 days prior to vaccination, have an acute disease or are in the acute attack of a chronic disease or have used antipyretic, analgesic and anti-allergic drugs (such as: acetaminophen, ibuprofen, aspirin, loratadine, ceti Rizine, etc.);
12. Receipt of inactivated or recombinant vaccines within 14 days, live vaccines within 28 days;
13. Receipt of immune globulin or blood-related products within 3 months; or plan to receive such products during this study period;
14. Had fever symptoms within 24 hours on the first day (aged> 14 years old, axillary temperature ≥ 37.3°C; aged ≤ 14 years old, axillary temperature ≥37.5°C );
15. Untreated/uncontrolled hypertension before vaccination (aged 9 to 17 years: systolic BP>120mmHg and/or diastolic BP>80mmHg; aged more than 18 years: Systolic BP≥140mmHg and/or diastolic BP ≥90mmHg);
16. Plan to permanently relocate from the area before the end of the study or leave the local area for a long time during the study visit (affecting the scheduled visit time);
17. According to the investigator's judgment, the subject has any condition may interfere with process of evaluation or participating in this study cannot guarantee the object's maximum benefit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 9-valent HPV vaccine; 9-valent HPV recombinant vaccine (Hansenula Polymorpha) All subjects aged 9 to 45 years received 3 doses of 9v HPV vaccine at 0,2,6 month scehdule	Biological: 9-valent HPV vaccine; 9-valent HPV recombinant vaccine (Hansenula Polymorpha) All subjects aged 9 to 45 years received 3 doses of 9v HPV vaccine at 0,2,6 month scehdule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary immunogenicity objective	The primary outcome measure for assessing vaccine immunogenicity, among subjects aged between 9 and 45, is the results of seroconversion rate of neutralizing antibodies after immunization in pre-immune negative subjects from 30 days after the last dose (3 doses schedule, Month 7) to HPV 6, 11, 16, 18, 31, 33, 45, 52 , and 58.	30 days after the last dose(3 doses schedule)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with postive antibodies after the whole schedule vaccination from the former negative subjects	The secondary outcome measure for assessing vaccine immunogenicity, among subjects aged between 9 and 45, is the geometric mean titer (GMT) from 30 days after the last dose (3 doses schedule, Month 7) to HPV 6, 11, 16, 18, 31, 33, 45, 52 , and 58.	30 days after the last dose(3 doses schedule)
Rate of seroconversion among the patient aged 9-26 after the whole schedule vaccination	To assess vaccine immunogenicity among the subjects aged between 9 and 26, is the seroconversion rate of neutralizing antibodies and the GMT from 30 days after the last dose (3 doses schedule, Month 7) to HPV 6, 11, 16, 18, 31, 33, 45, 52 , and 58.	30 days after the last dose(3 doses schedule)
GMT and seropositive rate of HPV in the 9-19 age group after 60-month follow-up	After receiving all 3 doses vaccinations, the subjects aged 9 to 19 years will be followed for 60 month (Month 12/24/36/48/60) after first vaccination to assess the GMT and seropositive rate (4-fold-increase) to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58.	Day 1 to 60 months post vaccination 3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of AE within 30 minutes after each dose	Adverse events reported within 30 minutes after each dose	30 mins after each dose
Number of SAE within 7days after each dose	Solicited adverse events reported between day 0 to day 7 after each dose	day 0 to day 7 after each dose
Number of unsolicited adverse events within 30days after each dose	Unsolicited adverse events reported between day 0 to day 30 after each dose	day 0 to day 30 after each dose
Number of all SAE during the study period	Serious adverse events reported during the study period	Stage 1: from month 6 to month 12 after the last dose; Stage 2: 6 month after receiving the whole vaccine schedule to 60 month after the 1st dose
Number and rate of pregnancy events	Pregnant event and pregnant outcome reported during the study period	Stage 1: from month 6 to month 12 after the last dose; Stage 2: 9-to-19-year-old subjects received 3 doses vaccinations, 6 month after receiving the whole vaccine schedule to 60 month after the 1st dose

Collaborators and Investigators

• Sponsor: Shanghai Bovax Biotechnology Co., Ltd.
• Collaborators: Chongqing Bovax Biopharmaceutical Co., Ltd.
• Investigators: Study Director: Person(s) responsible for the overall scientific leadership of Lv, Zhejiang Provincial Center for Disease Control and Prevention

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2021
• Primary Completion (Actual): January 13, 2023
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Virus Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Disease Attributes; DNA Virus Infections; Skin Diseases, Infectious; Warts; Skin Diseases, Viral; Tumor Virus Infections; Vaginal Diseases; Vulvar Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Vulvar Neoplasms; Papillomavirus Infections; Vaginal Neoplasms; Condylomata Acuminata
• Other Study ID Numbers: 9-HPV-3003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No