Evaluate the Immunogenicity and Safety of 9-valent HPV Recombinant Vaccine in Chinese Healthy Females

A Randomized, Double-Blind and Positive-Controlled Phase 3 Study to Evaluate the Immunogenicity and Safety of the 9-valent Human Papillomavirus (Types 6, 11, 16, 18,31,33,45,52 and 58) Recombinant Vaccine (Hansenula Polymorpha) in Chinese Female Subjects Aged16-26 Years

The study will evaluate the immunogenicity and safety of 9-valent HPV recombinant vaccine in Chinese healthy females16 to 26 years of age.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer; Vulvar Cancer; Vaginal Cancer; CIN1; CIN2; CIN3; VaIN1; VaIN2; VaIN3; Genital Wart; VIN 1; VIN 2; VIN 3; AIS; HPV Infections
• Intervention / Treatment: Biological: Experimental: Experimental: 9-valent Human Papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58); Biological: Active Comparator: GARDASIL ®9

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

Contacts and Locations

Study Locations

• China
  • Guangxi, China
    • Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 26 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

(If the "*" option is not met during screening, the visit can be rescheduled)

1. Chinese women aged 16-26 who can provide legal identification(If the subject is under 18 years old, proof of legal guardian's identity is also required);
2. The subject agreed to participate in the study, and voluntarily signs the informed consent;for subjects aged 16-18 years, they and their legal guardian(s) are supposed to understand and sign informed consent form together； supposed to understand and sign informed consent form together
3. Subjects are able to understand the study procedures and participate in follow-up according to the study requirements;
4. When the subjects were enrolled, the urine pregnancy test was negative, they were not in the lactation period and had no family planning within 7 months after enrollment.2 weeks before included in the study, effective contraceptive measures has been adopted and agreed to in the first seven months after the study (vaccinations after 1 months ago) continue to adopt effective contraceptive measures (effective contraceptive measures including the pill or condoms, etc ); 5.4. Have an acute illness or an acute episode of a chronic illness within 3 days prior to vaccination or the use of antipyretic, analgesic and antiallergic drugs (e.g., acetaminophen, ibuprofen, aspirin, loratadine, cetirizine, etc.);
5. *body temperature <37.3# (underarm body temperature)

Exclusion Criteria:

First dose exclusion criteria(If the "*" option is met during screening, the visit can be rescheduled)

1. Have been vaccinated with commercially available HPV vaccine in the past or planned to be vaccinated with commercially available HPV vaccine during the study period;Or have participated in a clinical trial of the HPV vaccine;
2. Has a history of cervical diseases, such as cervical screening showing abnormal results including CIN or a history of hysterectomy (vaginal or total abdominal hysterectomy) or pelvic radiation therapy. Has a history of genital diseases (such as vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, genital warts, vulvar cancer, vaginal cancer and anal cancer, etc.) or has a previous sexual history (including syphilis, gonorrhea, chancre, venereal lymphatic granuloma, granuloma inguinal);
3. A history of severe allergies requiring medical intervention, such as anaphylactic shock, anaphylactic laryngeal edema, allergic purpura, thrombocytopenic purpura, local allergic necrosis reaction (Arthus reaction), etc;
4. Subjects present with immune impairment or have been diagnosed with congenital or acquired immune deficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease or other autoimmune diseases. Long-term immunosuppressive therapy, e.g., long-term (more than 2 weeks) treatment with glucocorticoids (e.g., prednisone or similar drugs);
5. Has been diagnosed with a severe congenital malformation or chronic disease such as Down syndrome, heart disease, liver disease, kidney disease, diabetes, etc., which may interfere with the conduct or completion of the study;
6. Participating in other (drug or vaccine) clinical trials prior to enrollment or planning to participate during the study;
7. Has been diagnosed with an infectious disease, such as tuberculosis, viral hepatitis and/or HIV infection;
8. A history or family history of convulsions, epilepsy, encephalopathy and mental illness;
9. Have contraindications to intramuscular injection, such as having been diagnosed with thrombocytopenia, any coagulation disorder or receiving anticoagulant therapy;
10. Absence of a spleen, functional absence of a spleen, and absence or removal of a spleen in any case;
11. *Have an acute illness or an acute episode of a chronic illness within 3 days prior to vaccination or the use of antipyretic, analgesic and antiallergic drugs (e.g., acetaminophen, ibuprofen, aspirin, loratadine, cetirizine, etc.);
12. *Subjects received inactivated or recombinant vaccines within 14 days prior to study enrollment, or attenuated live vaccines within 28 days prior to study enrollment;
13. Subject receives any immunoglobulin or blood product within 3 months prior to the first dose of vaccination;
14. * after questioning, subjects had fever symptoms (subaxillary body temperature ≥37.3#) before the first day of vaccination (within 24 hours before vaccination);
15. Blood pressure on physical examination before the first dose of vaccination was higher than normal or increased (for subjects aged 16-17 year，systolic blood pressure ≥120mmHgand/or diastolic blood pressure ≥80mmHg，for subjects aged 18 year and above，systolic blood pressure ≥140mmHgand/or diastolic blood pressure ≥90mmHg);
16. Subjects may be unable to comply with the study procedure, comply with the agreement, or plan to permanently relocate from the region prior to completion of the study, or may be permanently absent from the region during the scheduled visit;
17. In the opinion of the investigators, the subjects had any other factors that made them unsuitable to participate in the clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental: 9-valent Human Papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58); 9-valent Human Papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52 and 58) Recombinant Vaccine (Hansenula Polymorpha),0.5mL, three doses, 0,2,6 months	Biological: Experimental: Experimental: 9-valent Human Papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58); 9vHPV vaccine ,0.5mL, three doses, 0,2,6 months
ACTIVE_COMPARATOR: GARDASIL ®9; GARDASIL®9 (Types 6, 11, 16, 18, 31, 33, 45, 52 and 58) ,0.5mL, three doses, 0,2,6 months	Biological: Active Comparator: GARDASIL ®9; GARDASIL®9 vaccine, 0.5mL, three doses, 0,2,6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome Measure	The primary outcome measure for assessing vaccine immunogenicity, among subjects aged between 16 and 26, is the results of seroconversion rate of neutralizing antibodies after immunization in pre-immune negative subjects from 30 days after the last dose HPV vaccine to HPV 6, 11, 16, 18, 31, 33, 45, 52 , and 58.	30 days after the last dose

Secondary 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 subjects with postive antibodies after the whole schedule vaccination from the former negative subjects	To evaluate the vaccine immunogenicity is the geometric mean titer from 30 days after the last dose to HPV 6, 11, 16, 18, 31, 33, 45, 52 , and 58.	30 days after the last dose
The level of neutralizing antibody elicited by the vaccine among the subjects with pre-immune positive after the whole schedule vaccination	The growth rate of GMTs of anti-HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58 neutralizing antibodies in pre-immune positive subjects from 30 days after immunization	30 days after the last dose
Number of subjects with seroconversion rate (4-fold increase) after the whole schedule vaccination	The seroconversion rate (4-fold increase) of anti-HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58 neutralizing antibodies in subjects aged 16-26-year-old from 30 days after immunization	30 days after the last dose
Number of all SAE during the study period	Serious adverse events reported during the study periodfrom 1st vaccination to the completion of study	Day 0 to 6 months post vaccination 3
Number and rate of pregnancy events	Pregnant event and pregnant outcome reported during the study period	Day 0 to 6 months post vaccination 3

Collaborators and Investigators

• Sponsor: Shanghai Bovax Biotechnology Co., Ltd.
• Collaborators: Chongqing Bovax Biopharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 19, 2020
• Primary Completion (ACTUAL): July 16, 2021
• Study Completion (ACTUAL): November 5, 2021

Study Registration Dates

• First Submitted: December 27, 2020
• First Submitted That Met QC Criteria: May 9, 2022
• First Posted (ACTUAL): May 12, 2022

Study Record Updates

• Last Update Posted (ACTUAL): May 12, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; DNA Virus Infections; Skin Diseases, Infectious; Warts; Skin Diseases, Viral; Tumor Virus Infections; Vaginal Diseases; Vulvar Diseases; Vulvar Neoplasms; Papillomavirus Infections; Vaginal Neoplasms; Condylomata Acuminata
• Other Study ID Numbers: 9-HPV-3002

Drug and device information, study documents

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