A Study to Evaluate the Immunogenicity, Safety and Tolerability of Quadrivalent Human Papillomavirus Vaccine (V501) in Chinese Girls Aged 9-19 Years and Young Women Aged 20-26 Years (V501-213)

Study Overview
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Brief Summary
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This study is designed to evaluate the immunogenicity, safety, and tolerability of Gardasil® (quadrivalent human papillomavirus [qHPV] vaccine, V501) in Chinese girls aged 9-19 years and young women aged 20-26 years. The primary hypothesis of the study states that at 1 month postdose 3, a 3-dose regimen of V501 induces non-inferior geometric mean titers (GMTs) for serum anti-HPV 6, anti-HPV 11, anti-HPV 16, anti-HPV 18 in girls aged 9-19 years compared to young women aged 20-26 years.

Detailed Description
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The study consists of a Base Stage wherein Chinese girls aged 9-19 years and young women aged 20-26 years receive a 3-dose regimen of V501 and are followed up to 1 month postdose 3 (Month 7). Participants aged 9-19 years who received 3 doses of V501 in the Base Stage will be eligible to participate in the Extension Stage and will be followed up to Month 60. No study vaccine will be administered during the Extension Stage.

Official Title
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A Phase 3 Open-Label Clinical Trial to Study the Immunogenicity, Safety and Tolerability of Recombinant Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Vaccine (V501) in Chinese Girls Aged 9-19 Years and Young Women Aged 20-26 Years

Conditions
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Prevention of HPV Types 16- and 18-related Cervical Cancer, Cervical Intraepithelial Neoplasia (CIN) 1/2/3, and Cervical Adenocarcinoma in Situ

Intervention / Treatment
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* Biological: V501


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Not pregnant and 1) not a woman of childbearing potential (WOCBP), or 2) a WOCBP who has not had sex with males or has had sex with males and used effective contraception since the first day of participant's last menstrual period through Day 1 and understands and agrees that during the study she should not have sexual intercourse with males without effective contraception (the rhythm method, withdrawal, and emergency contraception are not acceptable methods per the protocol). Participant and participant's parent or guardian (participants aged 9-17 years only) provided written informed consent/assent. Provided a primary and alternative telephone for follow-up purposes. Extension Stage: participant was enrolled in the 9-19 years old group, received 3 doses of V501 in the Base Stage, and participant and participant's legally acceptable representative (if applicable) provided written informed consent/assent for the study extension. Exclusion Criteria: History of severe allergic reaction that required medical intervention. Allergic to any vaccine component, including aluminum, yeast, or Benzonase® (nuclease). Known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections. Currently immunocompromised or was diagnosed as having congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, or other autoimmune condition. History of splenectomy. Any condition which in the opinion of the investigator might interfere with the evaluation of the study objectives. History of recent or ongoing alcohol or other drug abuse. History of a positive test for HPV. Any history of abnormal Pap test. History of external genital wart, vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), vulvar cancer or vaginal cancer. Undergone hysterectomy (either vaginal or total abdominal hysterectomy). Receiving or has received in the year prior to Day 1 vaccination an excluded immunosuppressive therapy. A participant will be excluded if she is currently receiving steroid therapy, has recently received such therapy, or has received 2 or more courses of corticosteroids (orally or parenterally) lasting at least 1 week in duration in the year prior to Day 1 vaccination. Participants using inhaled, nasal or topical steroids are considered eligible for the study. Received immune globulin product or blood-derived product within 6 months prior to Day 1 vaccination, or plans to receive any such product during the study. Received a marketed HPV vaccine, or has participated in an HPV vaccine clinical trial and has received either active agent or placebo. Received inactivated or recombinant vaccines within 14 days prior to Day 1 vaccination or receipt of live vaccines within 21 days prior to Day 1 vaccination. Concurrently enrolled in a clinical study of investigational agents. Had >4 lifetime sexual partners. Unlikely to adhere to the study procedures, keep appointments, or is planning to permanently relocate from the area prior to the completion of the study or to leave for an extended period of time when study visits would need to be scheduled. An immediate family member who is investigational site or sponsor staff directly involved with this study. Extension Stage: reported overdose or received non-study HPV vaccine during the Base Stage.

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 26 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chinese Girls Aged 9 to 19 Years<br>Participants will receive V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 | Biological: V501<br>* 0.5 mL intramuscular injection in the deltoid muscle at Day 1, Month 2, and Month 6<br>* Other names: qHPV;|
| Active Comparator: Chinese Young Women Aged 20 to 26 Years<br>Participants will receive V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 | Biological: V501<br>* 0.5 mL intramuscular injection in the deltoid muscle at Day 1, Month 2, and Month 6<br>* Other names: qHPV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers for Serum Anti-Human Papillomavirus (HPV) Types 6, 11, 16, and 18: Competitive Luminex Immunoassay (cLIA): Base Stage | Antibodies to HPV Types 6, 11, 16, and 18 were measured using a cLIA. Antibody titers were expressed as milli Merck Units/milliliter (mMU/mL). | Month 7 (1 month postdose 3) | 
| Antibody Titers as Measured by cLIA: Extension Stage | Geometric mean titers to HPV Types 6, 11, 16, and 18 will be assessed. Antibodies will be measured using a Competitive Luminex Immunoassay (cLIA). This Outcome Measure applies only to participants aged 9 to 19 years. | Month 12, 24, 36, 48, and 60 | 
| Seropositivity Rates as Measured by cLIA: Extension Stage: | The percentage of participants who are seropositive to each of HPV Types 6, 11, 16, and 18 will be assessed. Antibodies will be measured using cLIA. This Outcome Measure applies only to participants aged 9 to 19 years. | Month 12, 24, 36, 48, and 60 | 
| Antibody Titers as Measured by Immunoglobulin G Luminex Immunoassay: Extension Stage: | Geometric mean titers to HPV Types 6, 11, 16, and 18 will be assessed. Antibodies will be measured using an Immunoglobulin G Luminex Immunoassay (IgG LIA). This Outcome Measure applies only to participants aged 9 to 19 years. | Month 12, 24, 36, 48, and 60 | 
| Seropositivity Rates as Measured by IgG LIA: Extension Stage: | The percentage of participants who are seropositive to each of HPV Types 6, 11, 16, and 18 will be assessed. Antibodies will be measured using IgG LIA. This Outcome Measure applies only to participants aged 9 to 19 years. | Month 12, 24, 36, 48, and 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: cLIA: Base Stage | The percentage of participants who seroconverted to each of HPV Types 6, 11, 16, and 18 was assessed. Antibodies were measured using cLIA. | Month 7 (1 month postdose 3) | 
| Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: IgG LIA: Base Stage | Antibodies to HPV Types 6, 11, 16, and 18 were measured using an IgG LIA. Antibody titers were expressed as milli Merck Units/milliliter (mMU/mL). | Month 7 (1 month postdose 3) | 
| Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: IgG LIA: Base Stage | The percentage of participants who seroconverted to each of HPV Types 6, 11, 16, and 18 was assessed. Antibodies were measured using IgG LIA. | Month 7 (1 month postdose 3) | 
| Percentage of Participants With a Solicited Injection-site Adverse Event (AE): Base Stage | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited injection-site AEs included injection-site redness, swelling, induration, pain, and pruritus. | Up to 15 days after any vaccination | 
| Percentage of Participants With a Solicited Systemic AE: Base Stage | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited systemic AEs included hypersensitivity, headache, fatigue, vomiting, nausea, diarrhea, myalgia, pyrexia, and cough. | Up to 15 days after any vaccination | 
| Percentage of Participants Who Have a Serious Adverse Event (SAE): Base Stage | An SAE is an AE that results in death, is life threatening, requires hospitalization or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, according to medical or scientific judgment, may jeopardize the participant or requires medical or surgical intervention to prevent one of the other outcomes listed in the above definition. | Up to Month 7 (1 month postdose 3) | 
| Percentage of Participants With Any AE: Base Stage | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment | Up to 31 days after any vaccination | 
| Maximum Axillary Temperature: Merck Sharp & Dohme (MSD) Criteria: Base Stage | In the global studies, fever is defined as an oral temperature of ≥37.8°C or 100.0°F, which is equivalent to axillary temperature of ≥37.2°C, while the definition of fever is axillary temperature of ≥37.1°C in Chinese criteria. To be compliant to Chinese criteria, axillary temperatures of ≥37.1°C was considered as a fever in this study. Body temperature readings assessed orally were converted to the axillary equivalent. The percentage of participants with a maximum axillary or converted axillary temperature was summarized by temperature range. | Up to 5 days after any vaccination | 
| Serious Adverse Events: Extension Stage: | The percentage of participants with an SAE will be assessed. An SAE is an AE that results in death, is life threatening, requires hospitalization or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, according to medical or scientific judgment, may jeopardize the participant or requires medical or surgical intervention to prevent one of the other outcomes listed in the above definition. This Outcome Measure applies only to participants aged 9 to 19 years. | Up to Month 60 |