A Study of Gardasil (V501) in Preadolescents and Adolescents (V501-018)

Study Overview
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Brief Summary
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This study is to evaluate the safety, tolerability, and immune response of an investigational vaccine in preadolescent and adolescent boys and girls for the prevention of Human Papilloma Virus (HPV).

Detailed Description
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The original base protocol (V501-018)(NCT00092547) was extended in amendments V501-018-05 and -06 to provide 37 months of follow-up. Additionally, subjects in the Placebo Group during the base study were given 3 doses of open-label GARDASIL™ (V501) at Months 30, 32, and 36. The study was extended again in amendment V501-018-10(NCT00092547), titled A Long Term Immunogenicity, Safety, and Effectiveness Study of GARDASIL (Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine) Among Adolescents Who Received GARDASIL at 9-18 Years of Age to allow a follow-up period to Month 126.

Official Title
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A Safety and Immunogenicity Study of Quadrivalent HPV (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) Vaccine in Preadolescents and Adolescents (Base Study). A Long Term Immunogenicity, Safety, and Effectiveness Study of GARDASIL (Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine) Among Adolescents Who Received GARDASIL at 9-18 Years of Age (Extension Study).

Conditions
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Human, Papillomavirus Infections

Intervention / Treatment
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* Biological: V501
* Biological: Comparator: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adolescents and preadolescents with no prior sexual history Exclusion Criteria: Subjects with compromised immune system or have a history of severe allergic reaction

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: qHPV Vaccine in Base Study<br>Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6. | Biological: V501<br>* 0.5 mL intramuscular injection of V501<br>* Other names: GARDASIL™;|
| Placebo Comparator: Placebo in Base Study<br>Represents participants who were randomized into the Placebo Group, who received three 0.5 mL intramuscular injections of placebo at Day 1, Month 2, and Month 6. | Biological: Comparator: Placebo<br>* 0.5 mL intramuscular injection of placebo<br>|
| Experimental: qHPV Vaccine in Extension Study<br>Represents participants originally enrolled into the Placebo Group who continued in the study to receive 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36. | Biological: V501<br>* 0.5 mL intramuscular injection of V501<br>* Other names: GARDASIL™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Serious Adverse Experiences (SAEs) Through Month 18 | Tolerability as assessed by the number of participants with clinical adverse experiences through Month 18. A serious adverse event is any adverse event that results in death, is life threatening, results in a persistent or significant disability/incapacity, results in hospitalization or prolongs an existing hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose, or is considered an other important medical event based on medical judgment. | Up to Month 18 | 
| Number of Participants Reporting SAEs From Month 18 Through Month 37 | Tolerability as assessed by the number of participants with clinical adverse experiences from Month 18 through Month 37 | Month 18 to Month 37 | 
| Number of Participants Reporting Other (Non-serious) AEs Through Month 18 | Tolerability as assessed by the number of participants with clinical adverse experiences through Month 18 | Up to Month 18: Injection site AEs were collected from Days 1-5 and other non-serious AEs from Days 1-15 after any vaccination | 
| Percentage of Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 72 | A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18. | Month 72 (66 Months Post-dose 3 for the Original qHPV Vaccine Cohort and 36 months Post-dose 3 for the Extension Group) | 
| Geometric Mean Titers (GMTs) for Anti-HPV 6, 11, 16, and 18 at Month 72 |  | Month 72 (66 Months Post-dose 3 for the Original qHPV Vaccine Cohort and 36 months Post-dose 3 for the Extension Group) | 
| Geometric Mean Titers for Anti-HPV 6, 11, 16, and 18 at Month 96 |  | Month 96 (90 Months Post-dose 3 for Original qHPV Vaccine Group and 60 Months Post-dose 3 for Extension Group) | 
| Percentage of Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 96 | A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18. | Month 96 (90 Months Post-dose 3 for Original qHPV Vaccine Cohort and 60 Months Post-dose 3 for Extension Group) | 
| Geometric Mean Titers for Anti-HPV 6, 11, 16, and 18 at Month 126 |  | Month 126 (120 Months Post-dose 3 for Original qHPV Vaccine Cohort and 90 Months Post-dose 3 for Extension Group) | 
| Percentage of Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 126 | A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18. | Month 126 (120 Months Post-dose 3 for Original qHPV Vaccine Cohort and 90 Months Post-dose 3 for Extension Group) | 
| Number of Participants Reporting SAEs Related to Study Vaccine or to a Study Procedure in the Long-term Follow-up | A serious adverse event is any adverse event that results in death, is life threatening, results in a persistent or significant disability/incapacity, results in hospitalization or prolongs an existing hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose, or is considered an other important medical event based on medical judgment. SAEs considered by the investigator to be possibly, probably, or definitely related to study vaccine or a study procedure were reported. | Month 37 to Month 126 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 1 Postdose 3 (Month 7) | A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18. | Month 7 (1 Month Postdose 3) | 
| Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 12 Postdose 3 (Month 18). | A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18. | Month 18 (12 Months Post-dose 3) | 
| Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 18 Postdose 3 (Month 24) | A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18. | Month 24 (18 Months Post-dose 3) | 
| Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 24 Postdose 3 (Month 30) | A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18. | Month 30 (24 Months Post-dose 3) | 
| Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 31 Postdose 3 (Month 37). | A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18. | Month 37 (31 Months Post-dose 3) | 
| Percentage of Participants in the Extension Group Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 1 Postdose 3 of qHPV (Month 37) | A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18. | Month 37 (1 Month Post-dose 3 of qHPV) | 
| Geometric Mean Titers of Original qHPV Vaccine Cohort for Anti-HPV 6, 11, 16, and 18 at Month 1 Postdose 3 of qHPV Vaccine (Month 7) |  | Month 7 (1 Month Post-dose 3) | 
| Geometric Mean Titers of Original qHPV Vaccine Cohort for Anti-HPV 6, 11, 16, and 18 at Month 12 Postdose 3 of qHPV Vaccine (Month 18) |  | Month 18 (Month 12 Post-dose 3) | 
| Geometric Mean Titers of Original qHPV Vaccine Cohort for Anti-HPV 6, 11, 16, and 18 at Month 18 Postdose 3 of qHPV Vaccine (Month 24) |  | Month 24 (18 Months Post-dose 3) | 
| Geometric Mean Titers of Original qHPV Vaccine Cohort for Anti-HPV 6, 11, 16, and 18 at Month 24 Postdose 3 of qHPV Vaccine (Month 30) |  | Month 30 (24 Months Post-dose 3) | 
| Geometric Mean Titers of Original qHPV Vaccine Cohort for Anti-HPV 6, 11, 16, and 18 at Month 31 Postdose 3 of qHPV Vaccine (Month 37) |  | Month 37 (31 Months Post-dose 3) | 
| Geometric Mean Titers in the Extension Group for Anti-HPV 6, 11, 16, and 18 at Month 1 Postdose 3 of qHPV Vaccine (Month 37) |  | Month 37 (1 Month Post-dose 3 of qHPV) | 
| Combined Incidence of HPV 6/11/16/18-related Persistent Infection and HPV 6/11/16/18-related CIN, AIS, VIN, VaIN, Genital Warts, and Cervical/Vaginal/Vulvar Cancer in Females | The HPV types were determined by polymerase chain reaction (PCR) testing. The combined incidence of HPV 6/11/16/18-related persistent infection and HPV 6/11/16/18-related cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), genital warts, and cervical/Vaginal/vulvar cancer was assessed in female participants. | Up to Month 126 | 
| Combined Incidence of HPV 6/11/16/18-related Persistent Infection and HPV 6/11/16/18-related PIN, Genital Warts, and Penile/Perineal/Perianal Cancer in Males | The HPV types were determined by PCR testing. Combined incidence of HPV 6/11/16/18-related persistent infection and HPV 6/11/16/18-related penile/perineal/perianal intraepithelial neoplasia (PIN), genital warts, and penile/perineal/perianal cancer was assessed in male participants. | Up to Month 126 |