Clinical trial NCT00092547: A Study of Gardasil (V501) in Preadolescents and Adolescents (V501-018)
Official title: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Human
Papillomavirus Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2004-09-28
Enrollment: 1781
Sex: ALL
Minimum age (years): 9
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Reporting Serious Adverse Experiences (SAEs) Through Month 18
timeFrame: Up to Month 18
measure: Number of Participants Reporting SAEs From Month 18 Through Month 37
timeFrame: Month 18 to Month 37
measure: Number of Participants Reporting Other (Non-serious) AEs Through Month 18
timeFrame: 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
measure: Percentage of Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 72
timeFrame: Month 72 (66 Months Post-dose 3 for the Original qHPV Vaccine Cohort and 36 months Post-dose 3 for the Extension Group)
measure: Geometric Mean Titers (GMTs) for Anti-HPV 6, 11, 16, and 18 at Month 72
timeFrame: Month 72 (66 Months Post-dose 3 for the Original qHPV Vaccine Cohort and 36 months Post-dose 3 for the Extension Group)
measure: Geometric Mean Titers for Anti-HPV 6, 11, 16, and 18 at Month 96
timeFrame: Month 96 (90 Months Post-dose 3 for Original qHPV Vaccine Group and 60 Months Post-dose 3 for Extension Group)
measure: Percentage of Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 96
timeFrame: Month 96 (90 Months Post-dose 3 for Original qHPV Vaccine Cohort and 60 Months Post-dose 3 for Extension Group)
measure: Geometric Mean Titers for Anti-HPV 6, 11, 16, and 18 at Month 126
timeFrame: Month 126 (120 Months Post-dose 3 for Original qHPV Vaccine Cohort and 90 Months Post-dose 3 for Extension Group)
measure: Percentage of Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 126
timeFrame: Month 126 (120 Months Post-dose 3 for Original qHPV Vaccine Cohort and 90 Months Post-dose 3 for Extension Group)
measure: Number of Participants Reporting SAEs Related to Study Vaccine or to a Study Procedure in the Long-term Follow-up
timeFrame: Month 37 to Month 126
Secondary outcomes:
measure: Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 1 Postdose 3 (Month 7)
timeFrame: Month 7 (1 Month Postdose 3)
measure: Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 12 Postdose 3 (Month 18).
timeFrame: Month 18 (12 Months Post-dose 3)
measure: Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 18 Postdose 3 (Month 24)
timeFrame: Month 24 (18 Months Post-dose 3)
measure: Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 24 Postdose 3 (Month 30)
timeFrame: Month 30 (24 Months Post-dose 3)
measure: Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 31 Postdose 3 (Month 37).
timeFrame: Month 37 (31 Months Post-dose 3)
measure: 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)
timeFrame: Month 37 (1 Month Post-dose 3 of qHPV)
measure: 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)
timeFrame: Month 7 (1 Month Post-dose 3)
measure: 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)
timeFrame: Month 18 (Month 12 Post-dose 3)
measure: 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)
timeFrame: Month 24 (18 Months Post-dose 3)
measure: 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)
timeFrame: Month 30 (24 Months Post-dose 3)
measure: 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)
timeFrame: Month 37 (31 Months Post-dose 3)
measure: 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)
timeFrame: Month 37 (1 Month Post-dose 3 of qHPV)
measure: 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
timeFrame: Up to Month 126
measure: 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
timeFrame: Up to Month 126
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Reisinger KS, Block SL, Lazcano-Ponce E, Samakoses R, Esser MT, Erick J, Puchalski D, Giacoletti KE, Sings HL, Lukac S, Alvarez FB, Barr E. Safety and persistent immunogenicity of a quadrivalent human papillomavirus types 6, 11, 16, 18 L1 virus-like particle vaccine in preadolescents and adolescents: a randomized controlled trial. Pediatr Infect Dis J. 2007 Mar;26(3):201-9. doi: 10.1097/01.inf.0000253970.29190.5a.
citation: Perez G, Lazcano-Ponce E, Hernandez-Avila M, Garcia PJ, Munoz N, Villa LL, Bryan J, Taddeo FJ, Lu S, Esser MT, Vuocolo S, Sattler C, Barr E. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like-particle vaccine in Latin American women. Int J Cancer. 2008 Mar 15;122(6):1311-8. doi: 10.1002/ijc.23260.
citation: Ferris D, Samakoses R, Block SL, Lazcano-Ponce E, Restrepo JA, Reisinger KS, Mehlsen J, Chatterjee A, Iversen OE, Sings HL, Shou Q, Sausser TA, Saah A. Long-term study of a quadrivalent human papillomavirus vaccine. Pediatrics. 2014 Sep;134(3):e657-65. doi: 10.1542/peds.2013-4144. Epub 2014 Aug 18.
citation: Ferris DG, Samakoses R, Block SL, Lazcano-Ponce E, Restrepo JA, Mehlsen J, Chatterjee A, Iversen OE, Joshi A, Chu JL, Krick AL, Saah A, Das R. 4-Valent Human Papillomavirus (4vHPV) Vaccine in Preadolescents and Adolescents After 10 Years. Pediatrics. 2017 Dec;140(6):e20163947. doi: 10.1542/peds.2016-3947.
citation: Garland SM, Ault KA, Gall SA, Paavonen J, Sings HL, Ciprero KL, Saah A, Marino D, Ryan D, Radley D, Zhou H, Haupt RM, Garner EIO; Quadrivalent Human Papillomavirus Vaccine Phase III Investigators. Pregnancy and infant outcomes in the clinical trials of a human papillomavirus type 6/11/16/18 vaccine: a combined analysis of five randomized controlled trials. Obstet Gynecol. 2009 Dec;114(6):1179-1188. doi: 10.1097/AOG.0b013e3181c2ca21.