A Study to Evaluate the Safety, Immune Response, and Efficacy of Gardasil (V501) in Women (V501-019 AM4, EXT1, EXT2 [AM1]) - Full Text View

Purpose

This study is to assess the tolerability and efficacy of a vaccine being evaluated to reduce the incidence of human papillomavirus (HPV) infection and disease (external genital warts and vulvar, vaginal, and cervical cancer) in women.

Condition	Intervention	Phase
Healthy Papillomavirus Infection	Biological: Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine Biological: Comparator: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention
Official Title:	Safety, Immunogenicity, and Efficacy of Gardasil (V501 (Human Papilloma Virus [Types 6, 11, 16, 18] Recombinant Vaccine) in Mid-Adult Women - The FUTURE III (Females United to Unilaterally Reduce Endo/Ectocervical Cancer) Study

Resource links provided by NLM:

Genetics Home Reference related topics: hereditary multiple exostoses

MedlinePlus related topics: Cancer Cervical Cancer Genital Warts Vaginal Cancer Vulvar Cancer Warts

Drug Information available for: Human Papillomaviruses

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Combined Incidence of HPV 6/11/16/18 Related Persistent Infection, Genital Warts, Vulvar Intraepithelial Neoplasia (VIN), Vaginal Intraepithelial Neoplasia (VaIN), Vulvar Cancer, Vaginal Cancer, Cervical Dysplasia, AIS, and Cervical Cancer [ Time Frame: Base Study: through Month 48 ] [ Designated as safety issue: No ]
HPV 6/11/16/18: The four types of HPV (types 6/11/16/18) were determined by polymerase chain reaction (PCR) testing
Number of Participants With Vaccine-Related Serious Adverse Events (SAEs) [ Time Frame: Base Study: through Month 48 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Combined Incidence of HPV 6/11 Related Persistent Infection, Genital Warts, VIN, VaIN, Vulvar Cancer, Vaginal Cancer, Cervical Dysplasia, Adenocarcinoma In Situ (AIS), and Cervical Cancer [ Time Frame: Base Study: through Month 48 ] [ Designated as safety issue: No ]
HPV 6/11: The two types of HPV (types 6/11) were determined by PCR testing
Combined Incidence of HPV 31/33/35/52/58 Related Persistent Infection, Genital Warts, VIN, VaIN, Vulvar Cancer, Vaginal Cancer, Cervical Dysplasia, Cervical AIS, and Cervical Cancer [ Time Frame: Base Study: through Month 48 ] [ Designated as safety issue: No ]
This outcome measure was not analyzed because of diminished interest by experts in composite efficacy endpoints associated with these HPV types

Other Outcome Measures:

Combined Incidence of HPV 16/18 Related Persistent Infection, Genital Warts, VIN, VaIN, Vulvar Cancer, Vaginal Cancer, Cervical Dysplasia, Cervical AIS, and Cervical Cancer [ Time Frame: Base Study: through Month 48 ] [ Designated as safety issue: No ]
HPV 16/18: The two types of HPV (types 16/18) were determined by PCR testing

Enrollment:	3819
Study Start Date:	June 2004
Estimated Study Completion Date:	April 2016
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: qHPV Vaccine Gardasil	Biological: Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine Gardasil intramuscular injection in three 0.5 mL doses over 6 months.
Placebo Comparator: Placebo	Biological: Comparator: Placebo Placebo intramuscular injection in three 0.5 mL doses over 6 months.

Detailed Description:

The base study (V501-019) encompassed Day 1 through Month 7, during which time participants received randomly assigned Gardasil™ (qHPV vaccine) or placebo at Day 1, Month 2 and Month 6. Base study follow-up continued through Month 48.

The base study was extended in protocol V501-019-10 (EXT1). Participants who received placebo and participants who received only 1 dose of qHPV vaccine in the base study were offered a complete 3-dose qHPV vaccine regimen (administered at EXT1 Day 1, Month 2 and Month 6). Participants who received only 2 doses of qHPV vaccine in the base study were offered a single additional dose of qHPV vaccine (administered at EXT1 Day 1). Participants were followed to EXT1 Month 7.

A Long Term Follow-Up (LTFU) extension study V501-019-20 (EXT2) will observe the long term safety, effectiveness, and immunogenicity of GARDASIL™ in 1,600 women who participated in the base protocol in Colombia. Data will be collected over a period of 6-10 years following subjects' enrollment in the original base protocol.

Eligibility

Ages Eligible for Study:	24 Years to 45 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

No history of genital warts, VIN, or VaIN
Not pregnant and agrees to use effective contraception through Month 7 of the study
Additional criteria will be discussed with you by the physician

Exclusion Criteria:

Pregnant
Concurrently enrolled in a clinical study involving collection of cervical specimens
Previously received any HPV vaccine
History of severe allergic reaction that required medical intervention
Received any immune globulin or blood-derived products within 3 months prior to the first study injection
History of splenectomy, known immune disorders, or receiving immunosuppressives
Immunocompromised or diagnosed with HIV infection
Known thrombocytopenia or any coagulation disorders that could contraindicate intramuscular injections
History of recent or ongoing alcohol or drug abuse
Prior treatment for genital warts, VIN, or VaIN
History of cervical disease (ie, surgical treatment for cervical lesions)
Hysterectomy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00090220

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

Publications:

Muñoz N, Manalastas R Jr, Pitisuttithum P, Tresukosol D, Monsonego J, Ault K, Clavel C, Luna J, Myers E, Hood S, Bautista O, Bryan J, Taddeo FJ, Esser MT, Vuocolo S, Haupt RM, Barr E, Saah A. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24-45 years: a randomised, double-blind trial. Lancet. 2009 Jun 6;373(9679):1949-57. Epub 2009 Jun 1.

Velicer C, Zhu X, Vuocolo S, Liaw KL, Saah A. Prevalence and Incidence of HPV Genital Infection in Women. Sex Transm Dis. 2009 Jul 31; [Epub ahead of print]

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Matys K, Mallary S, Bautista O, Vuocolo S, Manalastas R, Pitisuttithum P, Saah A. Mother-infant transfer of anti-human papillomavirus (HPV) antibodies following vaccination with the quadrivalent HPV (type 6/11/16/18) virus-like particle vaccine. Clin Vaccine Immunol. 2012 Jun;19(6):881-5. Epub 2012 Apr 18.

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 EI; 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):1179-88.

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT00090220 History of Changes
Other Study ID Numbers:	V501-019, 2004_013
Study First Received:	August 25, 2004
Results First Received:	October 30, 2009
Last Updated:	August 14, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Papillomavirus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections

ClinicalTrials.gov processed this record on May 22, 2013