Dose-Ranging Study of Quadrivalent Human Papillomavirus (HPV) (Types 6,11,16,18) L1 Virus-Like Particle (VLP) Vaccine (V501-007)(COMPLETED) - Full Text View

Purpose

This study was conducted in 2 parts. Part A was a randomized, double-blind, placebo-controlled, multicenter, sequential dose-escalating evaluation. Part B was a randomized, double-blind (operating under in-house blinding procedures), placebo-controlled, multicenter, dose-ranging study.

Condition	Intervention	Phase
Papillomavirus Infections Genital Diseases, Female	Biological: Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20 Biological: Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40 Biological: Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80 Biological: Placebo (mcg) (Aluminum Adjuvant)225 Biological: Placebo (mcg) (Aluminum Adjuvant) 450	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention
Official Title:	A Placebo-Controlled, Dose-Ranging Study of Quadrivalent HPV Virus-Like Particle (VLP) Vaccine in 16- to 23-Year-Old Women

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Aluminum Human Papillomaviruses

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Number of Subjects With Injection Site Adverse Experiences [ Time Frame: Days 1-5 following any vaccination visit ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Incidence of HPV 6-, 11-, 16- or 18-related Persistent Infection or Disease (Cervical Intraepithelial Neoplasia, Vulvar Intraepithelial Neoplasia, Vaginal Intraepithelial Neoplasia, Adenocarcinoma in Situ, Cervical Cancer, and Genital Warts) [ Time Frame: Through 36 Months ] [ Designated as safety issue: No ]

Enrollment:	1158
Study Start Date:	May 2000
Study Completion Date:	September 2009
Primary Completion Date:	May 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 1 received a 20/40/40/20 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.	Biological: Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20 20/40/40/20 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6. Other Name: V501
Experimental: Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40 The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 2 received a 40/40/40/40 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.	Biological: Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40 40/40/40/40 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6. Other Name: V501
Experimental: Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80 The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 3 received a 80/80/40/80 formulation of quadrivalent human papillomavirus (qHPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.	Biological: Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80 80/80/40/80 formulation of quadrivalent human papillomavirus (qHPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6. Other Name: V501
Experimental: Placebo (mcg) (Aluminum Adjuvant) 225 The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 4 received placebo containing 225 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.	Biological: Placebo (mcg) (Aluminum Adjuvant)225 placebo containing 225 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
Experimental: Placebo (mcg) (Aluminum Adjuvant) 450 The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 5 received placebo containing 450 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.	Biological: Placebo (mcg) (Aluminum Adjuvant) 450 placebo containing 450 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.

Eligibility

Ages Eligible for Study:	16 Years to 23 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy females 16 to 23 years of age
Not pregnant at enrollment and must have agreed to use effective contraception through Month 7 of the study
Lifetime history of 0 to 4 male sexual partners (individuals with whom penetrative sexual intercourse occurred)

Exclusion Criteria:

No prior receipt of an Human Papillomavirus (HPV) vaccine
No receipt of inactivated or recombinant vaccines within 14 days prior to enrollment or receipt of live vaccines within 21 days prior to enrollment
No prior abnormal Pap test showing squamous intraepithelial lesion (SIL) or biopsy showing cervical intraepithelial neoplasia (CIN)
No prior history of genital warts or treatment for genital warts

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00365716

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

Publications:

Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR, Wheeler CM, Koutsky LA, Malm C, Lehtinen M, Skjeldestad FE, Olsson SE, Steinwall M, Brown DR, Kurman RJ, Ronnett BM, Stoler MH, Ferenczy A, Harper DM, Tamms GM, Yu J, Lupinacci L, Railkar R, Taddeo FJ, Jansen KU, Esser MT, Sings HL, Saah AJ, Barr E. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol. 2005 May;6(5):271-8.

Villa LL, Ault KA, Giuliano AR, Costa RL, Petta CA, Andrade RP, Brown DR, Ferenczy A, Harper DM, Koutsky LA, Kurman RJ, Lehtinen M, Malm C, Olsson SE, Ronnett BM, Skjeldestad FE, Steinwall M, Stoler MH, Wheeler CM, Taddeo FJ, Yu J, Lupinacci L, Railkar R, Marchese R, Esser MT, Bryan J, Jansen KU, Sings HL, Tamms GM, Saah AJ, Barr E. Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18. Vaccine. 2006 Jul 7;24(27-28):5571-83. Epub 2006 May 15.

Villa LL, Costa RL, Petta CA, Andrade RP, Paavonen J, Iversen OE, Olsson SE, Hoye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, Krogh G, Lehtinen M, Malm C, Tamms GM, Giacoletti K, Lupinacci L, Railkar R, Taddeo FJ, Bryan J, Esser MT, Sings HL, Saah AJ, Barr E. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer. 2006 Dec 4;95(11):1459-66. Epub 2006 Nov 21.

Barr E, Gause CK, Bautista OM, Railkar RA, Lupinacci LC, Insinga RP, Sings HL, Haupt RM. Impact of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle vaccine in a sexually active population of North American women. Am J Obstet Gynecol. 2008 Mar;198(3):261.e1-11.

Joura EA, Leodolter S, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, Garland SM, Harper DM, Tang GW, Ferris DG, Steben M, Jones RW, Bryan J, Taddeo FJ, Bautista OM, Esser MT, Sings HL, Nelson M, Boslego JW, Sattler C, Barr E, Paavonen J. Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials. Lancet. 2007 May 19;369(9574):1693-702.

Perez G, Lazcano-Ponce E, Hernandez-Avila M, García PJ, Muñoz 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.

Olsson SE, Villa LL, Costa RL, Petta CA, Andrade RP, Malm C, Iversen OE, Høye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, von Krogh G, Lehtinen M, Paavonen J, Tamms GM, Giacoletti K, Lupinacci L, Esser MT, Vuocolo SC, Saah AJ, Barr E. Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine. Vaccine. 2007 Jun 21;25(26):4931-9. Epub 2007 Apr 20.

Smith JF, Brownlow M, Brown M, Kowalski R, Esser MT, Ruiz W, Barr E, Brown DR, Bryan JT. Antibodies from women immunized with Gardasil cross-neutralize HPV 45 pseudovirions. Hum Vaccin. 2007 Jul-Aug;3(4):109-15. Epub 2007 Feb 24.

Ault KA; Future II Study Group. Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials. Lancet. 2007 Jun 2;369(9576):1861-8.

Giuliano AR, Lazcano-Ponce E, Villa L, Nolan T, Marchant C, Radley D, Golm G, McCarroll K, Yu J, Esser MT, Vuocolo SC, Barr E. Impact of baseline covariates on the immunogenicity of a quadrivalent (types 6, 11, 16, and 18) human papillomavirus virus-like-particle vaccine. J Infect Dis. 2007 Oct 15;196(8):1153-62. Epub 2007 Sep 17.

Responsible Party:	Executive Vice President, Clinical and Quantitative Sciences, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00365716 History of Changes
Other Study ID Numbers:	2006_516, V501-007
Study First Received:	August 16, 2006
Results First Received:	May 19, 2010
Last Updated:	March 27, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Merck:

HPV 6/11/16/18 infection and related genital disease

Additional relevant MeSH terms:

Genital Diseases, Female
Papillomavirus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections

Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013