Cervical Intraepithelial Neoplasm (CIN) in Women (Gardasil)(V501-015) - Full Text View

Sponsor:	Merck
Information provided by (Responsible Party):	Merck
ClinicalTrials.gov Identifier:	NCT00092534

Purpose

The primary purpose of the study is to determine if Gardasil (V501) an investigational vaccine with 4 components is able to prevent cervical cancer.

Condition	Intervention	Phase
Cervical Cancer Genital Warts	Biological: Gardasil, human papillomavirus (type 6, 11, 16, 18) recombinant vaccine Biological: Matching Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention
Official Title:	A Randomized, Worldwide, Placebo-Controlled, Double-Blind Study to Investigate the Safety Immunogenicity and Efficacy on the Incidence of HPV 16/18-Related CIN2/3 or Worse of the Quadrivalent HPV (Types 6, 11, 16, 18,) L1 Virus-Like Particle (VLP) Vaccine (V501, Gardasil) in 16- to 23-Year Old Women - The F.U.T.U.R.E. II Study (Females United to Unilaterally Reduce Endo/Ectocervical Disease)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Cervical Cancer Genital Warts Warts

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Tolerability; Incidence of the Composite Endpoint of HPV 16 or HPV 18 Related CIN2/3 or Invasive Cervical Carcinoma After Completion of the Vaccination Series for Relevant HPV Type [ Time Frame: Follow-up through end of study (4 years) ] [ Designated as safety issue: No ]
Tolerability = Number of subjected affected. Incidence Rate per person-years of follow-up.

The tolerability objective was to demonstrate that Gardasil is generally well tolerated by females aged 16-23. The relevant data are presented in the Reported Adverse Events section. No formal statistical hypothesis testing were performed for this objective.

Secondary Outcome Measures:

Subjects With Anti-HPV 6 Titer >/= 20 mMU/mL [ Time Frame: week 4 Postdose 3 (4 weeks after 3rd vaccine dose) ] [ Designated as safety issue: No ]
Subsequent to protocol registration, an updated serology assay was used in which seropositivity was defined as >/= 20 mMU/mL
Subjects With Anti-HPV 11 Titer >/= 16 mMU/mL [ Time Frame: week 4 Postdose 3 ] [ Designated as safety issue: No ]
Subsequent to protocol registration, an updated serology assay was used in which seropositivity was defined as >/= 16 mMU/mL
Subjects With Anti-HPV 16 Titer >/= 20 mMU/mL [ Time Frame: week 4 Postdose 3 ] [ Designated as safety issue: No ]
Subsequent to protocol registration, an updated serology assay was used in which seropositivity was defined as >/= 20mMU/mL
Subjects With Anti-HPV 18 Titer >/= 24 mMU/mL [ Time Frame: week 4 Postdose 3 ] [ Designated as safety issue: No ]
Subsequent to protocol registration, an updated serology assay was used in which seropositivity was defined as >/= 24 mMU/mL

Enrollment:	12167
Study Start Date:	June 2002
Estimated Study Completion Date:	January 2018
Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Quadrivalent Human Papillomavirus (HPV) Vaccine The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 1 were vaccinated (at Day 1, Month 2 and Month 6) with the Quadrivalent HPV vaccine.	Biological: Gardasil, human papillomavirus (type 6, 11, 16, 18) recombinant vaccine Duration of Treatment: 6 months Other Name: V501
Placebo Comparator: Placebo The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 2 were vaccinated (at Day 1, Month 2 and Month 6) with placebo.	Biological: Matching Placebo Matching Placebo to Quadrivalent Human Papillomavirus Vaccine

Detailed Description:

The original base study (V501-015) (NCT00092534) was extended in protocol V501-015-10. Subjects in the placebo arm of the base study were given 3 doses of open-label GARDASIL™ (V501) at Extension (EXT) Day 1, EXT Month 2 and EXT Month 6 and were followed to EXT Month 7. Subjects who received only 1 dose of GARDASIL™ in the base study were given 3 doses of open-label GARDASIL™ (V501) at Extension (EXT) Day 1, EXT Month 2 and EXT Month 6 and were followed to EXT Month 7. Subjects who received 2 doses of GARDASIL™ in the base study were given only 1 dose of GARDASIL™ at EXT Day 1 and were followed for 15 days (day of vaccination plus 14 days).

A second extension study, V501-015-20, will assess the effectiveness, immunogenicity and safety of GARDASIL™ during a period of 10-14 years following completion of the base study (V501-015) or the V501-015-10 extension. Subjects from Denmark, Iceland, Norway and Sweden who participated in the base study were eligible to enroll. Effectiveness and safety will be assessed by registry-based follow-up. Immunogenicity will be assessed by serological testing at approximately Year 5 and Year 10 of the V501-015-20 extension, respectively.

Eligibility

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

Criteria

Inclusion Criteria:

Healthy women with an intact uterus with lifetime history of 0-4 sexual partners

--For Extension Phase:
Subject received placebo or an incomplete vaccination series in the original study

Exclusion Criteria:

Prior Human Papilloma Virus (HPV) vaccination
Prior abnormal Paps
Prior history of genital warts

--For Extension Phase:
Prior complete HPV vaccination series
Subject lives in a country in which Gardasil is approved and is within the age range of the local labeling for Gardasil

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00092534

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

Publications:

FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007 May 10;356(19):1915-27.

Garland SM, Steben M, Sings HL, James M, Lu S, Railkar R, Barr E, Haupt RM, Joura EA. Natural History of Genital Warts: Analysis of the Placebo Arm of 2 Randomized Phase III Trials of a Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) Vaccine. J Infect Dis. 2009 Jan 26; [Epub ahead of print]

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.

FUTURE II Study Group. Prophylactic efficacy of a quadrivalent human papillomavirus (HPV) vaccine in women with virological evidence of HPV infection. J Infect Dis. 2007 Nov 15;196(10):1438-46. Epub 2007 Oct 31.

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.

Garland SM, Insinga RP, Sings HL, Haupt RM, Joura EA. Human papillomavirus infections and vulvar disease development. Cancer Epidemiol Biomarkers Prev. 2009 Jun;18(6):1777-84.

Skjeldestad FE, Mehta V, Sings HL, Øvreness T, Turpin J, Su L, Boerckel P, Roberts C, Bryan J, Jansen KU, Esser MT, Liaw KL. Seroprevalence and genital DNA prevalence of HPV types 6, 11, 16 and 18 in a cohort of young Norwegian women: study design and cohort characteristics. Acta Obstet Gynecol Scand. 2008;87(1):81-8.

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

Haupt RM, Wheeler CM, Brown DR, Garland SM, Ferris DG, Paavonen JA, Lehtinen MO, Steben M, Joura EA, Giacoletti KE, Radley DR, James MK, Saah AJ, Sings HL; FUTURE I and II Investigators. Impact of an HPV6/11/16/18 L1 virus-like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection. Int J Cancer. 2011 Dec 1;129(11):2632-42. Epub 2011 Apr 13.

Lehtinen M, Ault KA, Lyytikainen E, Dillner J, Garland SM, Ferris DG, Koutsky LA, Sings HL, Lu S, Haupt RM, Paavonen J; FUTURE I and II Study Group. Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia. Sex Transm Infect. 2011 Aug;87(5):372-6. Epub 2011 Apr 6.

Ault KA, Joura EA, Kjaer SK, Iversen OE, Wheeler CM, Perez G, Brown DR, Koutsky LA, Garland SM, Olsson SE, Tang GW, Ferris DG, Paavonen J, Steben M, Bosch FX, Majewski S, Muñoz N, Sings HL, Harkins K, Rutkowski MA, Haupt RM, Garner EI; FUTURE I and II Study Group. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine. Int J Cancer. 2011 Mar 15;128(6):1344-53. Epub 2011 Jan 12.

FUTURE I/II Study Group; Dillner J, Kjaer SK, Wheeler CM, Sigurdsson K, Iversen OE, Hernandez-Avila M, Perez G, Brown DR, Koutsky LA, Tay EH, García P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Lehtinen M, Steben M, Bosch FX, Joura EA, Majewski S, Muñoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan JT, Maansson R, Lu S, Vuocolo S, Hesley TM, Barr E, Haupt R. Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial. BMJ. 2010 Jul 20;341:c3493.

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.

Majewski S, Bosch FX, Dillner J, Iversen OE, Kjaer SK, Muñoz N, Olsson SE, Paavonen J, Sigurdsson K, Bryan J, Esser MT, Giacoletti K, James M, Taddeo F, Vuocolo S, Barr E. The impact of a quadrivalent human papillomavirus (types 6, 11, 16, 18) virus-like particle vaccine in European women aged 16 to 24. J Eur Acad Dermatol Venereol. 2009 Oct;23(10):1147-55. Epub 2009 Apr 23.

Brown DR, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, Tay EH, Garcia P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Steben M, Bosch FX, Dillner J, Joura EA, Kurman RJ, Majewski S, Muñoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Lupinacci LC, Giacoletti KE, Sings HL, James M, Hesley TM, Barr E. The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years. J Infect Dis. 2009 Apr 1;199(7):926-35.

Wheeler CM, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Perez G, Brown DR, Koutsky LA, Tay EH, García P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Steben M, Bosch FX, Dillner J, Joura EA, Kurman RJ, Majewski S, Muñoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Lupinacci LC, Giacoletti KE, James M, Vuocolo S, Hesley TM, Barr E. The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in sexually active women aged 16-26 years. J Infect Dis. 2009 Apr 1;199(7):936-44.

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT00092534 History of Changes
Other Study ID Numbers:	2004_082, V501-015
Study First Received:	September 23, 2004
Results First Received:	July 20, 2009
Last Updated:	January 4, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Uterine Cervical Neoplasms
Condylomata Acuminata
Cervical Intraepithelial Neoplasia
Carcinoma in Situ
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Warts

Papillomavirus Infections
DNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Skin Diseases, Viral
Tumor Virus Infections
Skin Diseases, Infectious
Skin Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on February 09, 2012