Lot Consistency Clinical Trial of Bivalent HPV Vaccine in 9 to 30 Years Old Healthy Females

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immunogenicity and safety of three consecutive lots of bivalent HPV (Type 16,18) vaccine (Pichia pastoris) in healthy female subjects aged 9 - 30 years, and demonstrate the non-inferiority of the candidate HPV vaccine manufactured at commercial scale compared with a pilot scale.

Official Title
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A Phase III, Randomized, Double-blind Study to Assess the Consistency of the Immunogenicity of Three Consecutive Production Lots of Bivalent HPV Vaccine in Healthy Female Subjects Aged 9 - 30 Years and to Demonstrate Non-inferiority of the Candidate HPV Vaccine Manufactured at Commercial Scale Compared With a Pilot Scale

Conditions
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HPV Infection

Intervention / Treatment
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* Biological: Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine (Pichia pastoris)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 9-30 healthy female able to provide legal identification. Written informed consent had to be obtained from the subject prior to enrolment (for subjects below the legal age of consent, written informed consent had to be obtained from a parent or legal guardian of the subject and, in addition, the subject had to sign and personally date a written informed assent). Women of child-bearing age(WOCBA): Subject had to have a negative urine pregnancy test, no plan to be pregnant in 7 months, and agree to use adequate contraceptive precautions during study period. Exclusion Criteria: Subject has received a marketed HPV vaccine or participated in an HPV vaccine clinical trial. History of abnormal cervical screen test result (ASC-US or worse) or history of genital warts. History of severe allergic reaction that required medical intervention. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccines. Pregnant or breastfeeding, or within 6 weeks after the end of pregnancy. Fever prior to vaccination (auxiliary temperature ≥37.3 °C). Hypertension (physical examination systolic blood pressure 140mmHg and or diastolic blood pressure 90mmHg. Received live attenuated vaccine within 15 days before vaccination or subunit or inactivated vaccine within 7 days. Received immunoglobulin and/or blood product 3 months prior to the first vaccination. Acute diseases or acute stage of the chronic diseases within 3 days preceding the vaccination. According to the judgment of the investigator, subject has or had any other symptoms, medical history and other factors that are not suitable for participating in this clinical trial.

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2vHPV Consistency Lot 1<br> | Biological: Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine (Pichia pastoris)<br>* sterile solution for intramuscular injection<br>|
| Experimental: 2vHPV Consistency Lot 2<br> | Biological: Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine (Pichia pastoris)<br>* sterile solution for intramuscular injection<br>|
| Experimental: 2vHPV Consistency Lot 3<br> | Biological: Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine (Pichia pastoris)<br>* sterile solution for intramuscular injection<br>|
| Active Comparator: 2vHPV Pilot Scale Lot<br> | Biological: Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine (Pichia pastoris)<br>* sterile solution for intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) for HPV-16 and/or HPV-18 at one month post 3rd dose |  | At Month 7 | 
| Percentage of participants who seroconvert to HPV-16 and/or HPV-18 at one month post 3rd dose | Seroconversion was defined as: For initially seronegative subjects [antibody titer below (<) 1:40 prior to vaccination], antibody titer greater than or equal to (≥) 1:40 after vaccination; For initially seropositive subjects (antibody titer ≥ 1:40 prior to vaccination), antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. | At Month 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (TEAE) during 30 days after each dose |  | 0 30 days after each vaccination | 
| Incidence of solicited adverse events (AEs) after vaccination |  | 0 7 days after each vaccination | 
| Incidence of unsolicited AEs after vaccination |  | 0 30 days after each vaccination | 
| Incidence of serious adverse events (SAEs) |  | Month 0 to Month 7 |