Clinical trial NCT04537156: Efficacy, Immunogenicity and Safety Study of Recombinant Human Papillomavirus Vaccine(6,11,16,18,31,33,45,52,58 Type)(E.Coli)
Official title: A Multicenter, Randomized, Double-Blind, Controlled (Bivalent Human Papillomavirus Vaccine (16,18 Type)(E. Coli)) Phase III Clinical Trial to Estimate Efficacy, Immunogenicity and Safty of the Recombinant Human Papillomavirus Vaccine (6,11,16,18,31,33,45,52,58 Type) (E.Coli) in Healthy Women Aged 18 to 45 Years
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Cervical Intraepithelial Neoplasia
Cervical Cancer
Condylomata Acuminata
Keywords: human papillomavirus vaccine
cervical cancer
cervical intraepithelial neoplasia
condylomata acuminata
Lead sponsor: Xiamen University
Sponsor class: OTHER
Collaborators: name: Xiamen Innovax Biotech Co., Ltd
name: Beijing Wantai Biological Pharmacy Enterprise Co., Ltd.
First posted: 2020-09-03
Enrollment: 9327
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This phase III clinical study was designed to evaluate the efficacy,immunogenicity and safety of Recombinant Human Papillomavirus Vaccine (6,11,16,18,31,33,45,52,58 Type)(E.Coli) manufactured by Xiamen Innovax Biotech CO., LTD., in healthy women aged 18-45 years old.


Eligibility criteria: Inclusion Criteria:

1. Female aged between 18 and 45 years at the first vaccination;
2. Be able to understand and comply with the request of the protocol(e.g. biological specimen collection, diary card entry and attend regular follow-up), and sign written informed consent;
3. Women who agree to use effective contraception within 8 months after the first vaccination, or women who have undergone tubal ligation, benign subtotal hysterectomy, benign ovarian tumor removal, or postmenopausal women;
4. The number of sexual partners so far less than four;
5. Have intact cervix and have no history of physical or surgical treatment;
6. No previous history of sexually transmitted diseases (including syphilis, gonorrhea, chancroid, venereal lymphogranuloma, groin granuloma, etc.);
7. No previous history of abnormal cervical screening results or cervical intraepithelial neoplasia (CIN), and no abnormality in gynecological examination;
8. Sexual intercourse has occurred.

Exclusion Criteria:

1. Participants with acute cervicitis and acute lower genital tract infection, or with obvious condyloma;
2. Participants during menstruation, or have vaginal medication, sexual behavior (including anal, vaginal or external genital contact, regardless of the sex of parterner) within two days (48 hours) before the visit, which may affect gynecological examinations and specimens collection.
3. Axillary temperature \> 37.0℃;
4. Participants who have positive urine pregnancy test, or are pregnant or breastfeeding;
5. Have used other investigational or unregistered products (drugs or vaccines) within 30 days before receiving the research vaccine or have participated in another clinical research in the past two years, or plan to use other research or unregistered products or participate in other research during the research period;
6. Long-term use (more than 14 continuous days) of immunosuppressors and other Immunoregulatory agents or systemic corticosteroids (Except intranasal steroid, the use of low dose topical, ophthalmic and inhaled steroid preparations will be permitted.) 6 months prior to vaccination.
7. Administration of immunoglobulin and/or blood products 3 months prior to vaccination or intending to use them during the study.
8. Administration of inactivated vaccine within 14 days before vaccination or live vaccine within 21 days;
9. Fever (Axillary temperature \>38.0℃) 3 days prior to vaccination or system administration of antibiotics or antiviral agents (Anti-flu agents include but are not limited to Tamiflu, Tamiflu, Symmetrel and Flumadine) 5 days prior to vaccination.
10. Have received other HPV vaccines or participated in clinical research related to HPV or cervical cancer previously;
11. Immunodeficiency disease, primary disease of important viscera, cancer and autoimmune disease (including systemic lupus erythematosus, rheumatoid arthritis, asplenia or splenectomy due to any condition, and other autoimmune diseases that investigators believe may influence the immune response).
12. History of severe allergy (e.g., anaphylaxis, generalized urticaria, dyspnea, angioedema, and other significant reaction) to any previous vaccines, or allergy to any of the components of investigational vaccine.
13. Asthma, which has been unstable for the past two years and requires emergency treatment, hospitalization, oral or intravenous corticosteroids;
14. Suffered from a serious medical illness;
15. Self-report past coagulation disorders or abnormal coagulation function;
16. Epilepsy, excluding febrile epilepsy under 2 years of age, alcoholic epilepsy 3 years prior to abstinence or simple epilepsy that did not require treatment in the past 3 years;
17. According to the judgement of investigator, various medical, psychological, social, vocational or other factors that are not suitable for participating in the clinical trial.

Primary outcomes:
measure: Non-inferiority of anti-HPV 16 and 18 seroconversion rates and geometric mean concentrations at Months 7 (type specific neutralizing antibody) in the PPS-I set
timeFrame: Specific neutralizing antibodies at 7 months after first dose
measure: Persistent infection of HPV31, 33, 45, 52 and 58 (over 12 months) (Combined analysis of the 5 types) in the mITT-PI set
timeFrame: Cumulative incidence of this endpoint events in 78 months after the first dose
measure: Incidence of CIN2 + and/or VIN2 + and/or VaIN2 + lesions related to HPV 31, 33, 45, 52 or 58 (Combined analysis of the 5 types) in the mITT-E when the first two endpoints are satisfied
timeFrame: Cumulative incidence of this endpoint events in 78 months after the first dose
Secondary outcomes:
measure: Efficacy1: Incidence of CIN2 + and/or VIN2 + and/or VaIN2 + lesions related to HPV 31, 33, 45, 52 or 58(Combined analysis of the 5 types) and genital warts related to HPV 6, 11 (Combined analysis of each type)
timeFrame: Cumulative incidence of this endpoint events in 78 months after the first dose
measure: Efficacy2: Incidence of CIN1 + and/or VIN1 + and/or VaIN1 + lesions related to HPV 31, 33, 45, 52 or 58(Combined analysis of the 5 types) and genital warts related to HPV 6, 11 (Combined analysis of each type)
timeFrame: Cumulative incidence of this endpoint events in 78 months after the first dose
measure: Efficacy3: Incidence of Persistent infection of HPV31, 33, 45, 52 and 58 (transient infection and over 6 months) (Combined analysis of the 5 types)
timeFrame: Cumulative incidence of this endpoint events in 78 months after the first dose
measure: Efficacy4: Incidence of CIN1 + and/or VIN1 + and/or VaIN1 + lesions related to HPV 31, 33, 45, 52 or 58(Combined analysis of the 5 types)
timeFrame: Cumulative incidence of this endpoint events in 78 months after the first dose
measure: Efficacy5: Incidence of Persistent infection of HPV31, 33, 45, 52 and 58 (over 6 months) and/or incidence of CIN1 + and/or VIN1 + and/or VaIN1 + lesions related to HPV 31, 33, 45, 52 or 58(Combined analysis of the 5 types)
timeFrame: Cumulative incidence of this endpoint events in 78 months after the first dose
measure: Efficacy6: Incidence of genital warts related to HPV 6, 11
timeFrame: Cumulative incidence of this endpoint events in 78 months after the first dose
measure: Efficacy7: Incidence of Persistent infection of HPV31, 33, 45, 52, 58, 6 and 11 (transient infection and over 6 months and over 12 months) (Combined analysis of the 7 types)
timeFrame: Cumulative incidence of this endpoint events in 78 months after the first dose
measure: Efficacy8: Incidence of Persistent infection of HPV31, 33, 45, 52, 58, 6 and 11 (over 6 months and over 12 months) (Independent analysis of each type)
timeFrame: Cumulative incidence of this endpoint events in 78 months after the first dose
measure: Immunogenicity1: Anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 seroconversion rates and geometric mean concentrations at Months 7
timeFrame: Month 7 after first vaccination
measure: Immunogenicity2: Anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 seroconversion rates and geometric mean concentrations at Months 18 and 30
timeFrame: Month 18 and 30 after first vaccination
measure: Immunogenicity3: Anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 seroconversion rates and geometric mean concentrations at Months 42, 54, 66 and 78
timeFrame: Month 42, 54, 66 and 78 after first vaccination
measure: Safety1: Local and systematic adverse events/reactions occurred within 7 days after each vaccination
timeFrame: During the 7-day (Day 0-6) period following each vaccination
measure: Safety2: Adverse events/reactions occurred within 30 days after each vaccination
timeFrame: Within 30 days (Day 0-30) after any vaccination
measure: Safety3: Serious adverse events occurred throughout the study
timeFrame: Up to 78 month
measure: Safety4: Pregnancy and pregnancy outcome
timeFrame: Up to 78 month
measure: Safety5: Emerging chronic diseases
timeFrame: Up to 78 month
Other outcomes:
measure: Incidence of CIN2 + and/or VIN2 + and/or VaIN2 + lesions related to HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 or 68 (Combined analysis of the high risk types)
timeFrame: Cumulative incidence of this endpoint events in 78 months after the first dose
measure: Incidence of CIN1 + and/or VIN1 + and/or VaIN1 + lesions related to HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 or 68 (Combined analysis of the high risk types)
timeFrame: Cumulative incidence of this endpoint events in 78 months after the first dose
measure: Incidence of Persistent infection of HPV35, 39,51,56,59 and 68 (total infection and over 6 months and over 12 months) (Independent analysis of each type)
timeFrame: Cumulative incidence of this endpoint events in 78 months after the first dose
Locations:
city: Nanjing
country: China
facility: Jiangsu Provincial Centre for Disease Control and Prevention
state: Jiangsu
city: Chengdu
country: China
facility: Sichuan Provincial Centre for Disease Control and Prevention
state: Sichuan
Study officials:
affiliation: Xiamen University
name: Jun Zhang, master
role: STUDY_CHAIR
affiliation: Jiangsu Provincial Centre for Disease Control and Prevention
name: Feng-cai Zhu, master
role: PRINCIPAL_INVESTIGATOR
References: