Efficacy, Immunogenicity and Safety Study of Recombinant Human Papillomavirus Vaccine(6,11,16,18,31,33,45,52,58 Type)(E.Coli)
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 Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Jiangsu
-
Nanjing, Jiangsu, China, 210009
- Jiangsu Provincial Centre for Disease Control and Prevention
-
-
Sichuan
-
Chengdu, Sichuan, China, 610041
- Sichuan Provincial Centre for Disease Control and Prevention
-
-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Female aged between 18 and 45 years at the first vaccination;
- 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;
- 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;
- The number of sexual partners so far less than four;
- Have intact cervix and have no history of physical or surgical treatment;
- No previous history of sexually transmitted diseases (including syphilis, gonorrhea, chancroid, venereal lymphogranuloma, groin granuloma, etc.);
- No previous history of abnormal cervical screening results or cervical intraepithelial neoplasia (CIN), and no abnormality in gynecological examination;
- Sexual intercourse has occurred.
Exclusion Criteria:
- Participants with acute cervicitis and acute lower genital tract infection, or with obvious condyloma;
- 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.
- Axillary temperature > 37.0℃;
- Participants who have positive urine pregnancy test, or are pregnant or breastfeeding;
- 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;
- 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.
- Administration of immunoglobulin and/or blood products 3 months prior to vaccination or intending to use them during the study.
- Administration of inactivated vaccine within 14 days before vaccination or live vaccine within 21 days;
- 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.
- Have received other HPV vaccines or participated in clinical research related to HPV or cervical cancer previously;
- 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).
- 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.
- Asthma, which has been unstable for the past two years and requires emergency treatment, hospitalization, oral or intravenous corticosteroids;
- Suffered from a serious medical illness;
- Self-report past coagulation disorders or abnormal coagulation function;
- 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;
- According to the judgement of investigator, various medical, psychological, social, vocational or other factors that are not suitable for participating in the clinical trial.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: HPV vaccine (6,11,16,18,31,33,45,52,58 Types)
Participants in this arm would receive 270μg/0.5ml HPV vaccines (6,11,16,18,31,33,45,52,58 Types).
|
Nonavalent HPV vaccine (270μg/0.5ml)
administered intramuscularly according to a 0, 1, 6 month vaccination schedule.
|
|
Active Comparator: HPV vaccine (16,18 Types)
Participants in this arm would receive 60μg/0.5ml
HPV vaccines (16,18 Types).
|
Bivalent HPV vaccine (60μg/0.5ml)
administered intramuscularly according to a 0, 1, 6 month vaccination schedule.
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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
Time Frame: Specific neutralizing antibodies at 7 months after first dose
|
Detect the level of anti-HPV 16 and 18 specific neutralizing antibodies at one month after the third dose to determine whether nine-valent HPV vaccine is non-inferior to the control bivalent HPV vaccine
|
Specific neutralizing antibodies at 7 months after first dose
|
|
Persistent infection of HPV31, 33, 45, 52 and 58 (over 12 months) (Combined analysis of the 5 types) in the mITT-PI set
Time Frame: Cumulative incidence of this endpoint events in 78 months after the first dose
|
To evaluate the efficacy of the nine-valent vaccine against this outcome compared with the control vaccine
|
Cumulative incidence of this endpoint events in 78 months after the first dose
|
|
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
Time Frame: Cumulative incidence of this endpoint events in 78 months after the first dose
|
To evaluate the efficacy of the nine-valent vaccine against this outcome compared with the control vaccine
|
Cumulative incidence of this endpoint events in 78 months after the first dose
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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)
Time Frame: Cumulative incidence of this endpoint events in 78 months after the first dose
|
To evaluate the efficacy of the nine-valent vaccine against this outcome compared with the control vaccine
|
Cumulative incidence of this endpoint events in 78 months after the first dose
|
|
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)
Time Frame: Cumulative incidence of this endpoint events in 78 months after the first dose
|
To evaluate the efficacy of the nine-valent vaccine against this outcome compared with the control vaccine
|
Cumulative incidence of this endpoint events in 78 months after the first dose
|
|
Efficacy3: Incidence of Persistent infection of HPV31, 33, 45, 52 and 58 (transient infection and over 6 months) (Combined analysis of the 5 types)
Time Frame: Cumulative incidence of this endpoint events in 78 months after the first dose
|
To evaluate the efficacy of the nine-valent vaccine against this outcome compared with the control vaccine
|
Cumulative incidence of this endpoint events in 78 months after the first dose
|
|
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)
Time Frame: Cumulative incidence of this endpoint events in 78 months after the first dose
|
To evaluate the efficacy of the nine-valent vaccine against this outcome compared with the control vaccine
|
Cumulative incidence of this endpoint events in 78 months after the first dose
|
|
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)
Time Frame: Cumulative incidence of this endpoint events in 78 months after the first dose
|
To evaluate the efficacy of the nine-valent vaccine against this outcome compared with the control vaccine
|
Cumulative incidence of this endpoint events in 78 months after the first dose
|
|
Efficacy6: Incidence of genital warts related to HPV 6, 11
Time Frame: Cumulative incidence of this endpoint events in 78 months after the first dose
|
To evaluate the efficacy of the nine-valent vaccine against this outcome compared with the control vaccine
|
Cumulative incidence of this endpoint events in 78 months after the first dose
|
|
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)
Time Frame: Cumulative incidence of this endpoint events in 78 months after the first dose
|
To evaluate the efficacy of the nine-valent vaccine against this outcome compared with the control vaccine
|
Cumulative incidence of this endpoint events in 78 months after the first dose
|
|
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)
Time Frame: Cumulative incidence of this endpoint events in 78 months after the first dose
|
To evaluate the efficacy of the nine-valent vaccine against this outcome compared with the control vaccine
|
Cumulative incidence of this endpoint events in 78 months after the first dose
|
|
Immunogenicity1: Anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 seroconversion rates and geometric mean concentrations at Months 7
Time Frame: Month 7 after first vaccination
|
Analysis the seroconversion and geometric mean concertration of the type specific antibodies of the 7 types.
|
Month 7 after first vaccination
|
|
Immunogenicity2: Anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 seroconversion rates and geometric mean concentrations at Months 18 and 30
Time Frame: Month 18 and 30 after first vaccination
|
Analysis the seroconversion and geometric mean concertration of the type specific antibodies of the 7 types.
|
Month 18 and 30 after first vaccination
|
|
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
Time Frame: Month 42, 54, 66 and 78 after first vaccination
|
Analysis the seroconversion and geometric mean concertration of the type specific antibodies of the 7 types.
|
Month 42, 54, 66 and 78 after first vaccination
|
|
Safety1: Local and systematic adverse events/reactions occurred within 7 days after each vaccination
Time Frame: During the 7-day (Day 0-6) period following each vaccination
|
safety analysis
|
During the 7-day (Day 0-6) period following each vaccination
|
|
Safety2: Adverse events/reactions occurred within 30 days after each vaccination
Time Frame: Within 30 days (Day 0-30) after any vaccination
|
safety analysis
|
Within 30 days (Day 0-30) after any vaccination
|
|
Safety3: Serious adverse events occurred throughout the study
Time Frame: Up to 78 month
|
safety analysis.
To evaluate number of SAEs compared with the control vaccine.
|
Up to 78 month
|
|
Safety4: Pregnancy and pregnancy outcome
Time Frame: Up to 78 month
|
safety analysis.
To evaluate number of births and terminations compared with the control vaccine.
|
Up to 78 month
|
|
Safety5: New-onset acute and chronic diseases (especially autoimmune diseases)
Time Frame: Up to 78 month
|
safety analysis.To evaluate number of new-onset acute and chronic diseases (especially new-onset autoimmune diseases) throughout the study.
|
Up to 78 month
|
Other Outcome Measures
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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)
Time Frame: Cumulative incidence of this endpoint events in 78 months after the first dose
|
To evaluate the efficacy of the nine-valent vaccine against this outcome compared with the control vaccine
|
Cumulative incidence of this endpoint events in 78 months after the first dose
|
|
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)
Time Frame: Cumulative incidence of this endpoint events in 78 months after the first dose
|
To evaluate the efficacy of the nine-valent vaccine against this outcome compared with the control vaccine
|
Cumulative incidence of this endpoint events in 78 months after the first dose
|
|
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)
Time Frame: Cumulative incidence of this endpoint events in 78 months after the first dose
|
To evaluate the efficacy of the nine-valent vaccine against this outcome compared with the control vaccine
|
Cumulative incidence of this endpoint events in 78 months after the first dose
|
Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Investigators
Investigators
- Study Chair: Jun Zhang, master, Xiamen University
- Principal Investigator: Hong-xing Pan, master, Jiangsu Provincial Centre for Disease Control and Prevention
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Estimated)
Primary Completion
Study Completion (Estimated)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Estimated)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Keywords
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
- Skin Diseases
- Precancerous Conditions
- Uterine Cervical Diseases
- Skin Diseases, Infectious
- Uterine Neoplasms
- Tumor Virus Infections
- Skin Diseases, Viral
- Papillomavirus Infections
- Warts
- Pathological Conditions, Signs and Symptoms
- Skin and Connective Tissue Diseases
- Uterine Cervical Neoplasms
- Uterine Cervical Dysplasia
- Condylomata Acuminata
- Immunologic Factors
- Physiological Effects of Drugs
- human papillomavirus vaccine, L1 type 16, 18
Other Study ID Numbers
Other Study ID Numbers
- HPV-PRO-009
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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