Cervical Intraepithelial Neoplasm (CIN)-Warts Efficacy Trial in Women (Gardasil)(V501-013)(COMPLETED)

Conditions

Cervical Cancer, Genital Warts

Brief summary

The primary purpose of the study is to determine if GARDASIL (V501) with four components is able to prevent cervical cancer, cervical dysplasia, including Cervical Intraepithelial Neoplasia (CIN)(Any Grade) and Adenocarcinoma In Situ (AIS), and genital warts.

Joura E, Kjaer SK, Bautista O, Luxembourg A, Saah A, Giuliano A.

2025-10-301 citations

10.1097/aog.0000000000006113

Adjuvant-containing control arms in pivotal quadrivalent human papillomavirus vaccine trials: restoration of previously unpublished methodology

Peter Doshi, Florence T. Bourgeois, Kyungwan Hong, Mark Jones, Haeyoung Lee et al. (8 authors)

BMJ evidence-based medicine2020-03-179 citations

10.1136/bmjebm-2019-111331

Nine-valent HPV vaccine efficacy against related diseases and definitive therapy: comparison with historic placebo population

Anna R. Giuliano, Elmar A. Joura, Suzanne M. Garland, Warner K. Huh, Ole-Erik Iversen et al. (15 authors)

Gynecologic Oncology2019-04-1190 citations

10.1016/j.ygyno.2019.03.253

Human Papillomavirus Genotypes From Vaginal and Vulvar Intraepithelial Neoplasia in Females 15–26 Years of Age

Suzanne M. Garland, Elmar A. Joura, Kevin A. Ault, F. Xavier Bosch, Darron R. Brown et al. (31 authors)

Obstetrics and Gynecology2018-07-1137 citations

10.1097/aog.0000000000002736

Proximity of first sexual intercourse to menarche and risk of high-grade cervical disease.

Ruiz ÁM, Ruiz JE, Gavilanes AV, Eriksson T, Lehtinen M, Pérez G, Sings HL, James MK, Haupt RM, FUTURE I and II Study Group.

2012-10-1211 citations

10.1093/infdis/jis612

Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data.

Joura EA, Garland SM, Paavonen J, Ferris DG, Perez G, Ault KA, Huh WK, Sings HL, James MK, Haupt RM, FUTURE I and II Study Group.

2012-03-27196 citations

10.1136/bmj.e1401

Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia.

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.

2011-04-0656 citations

10.1136/sti.2010.044354

Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial.

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.

2010-07-20260 citations

10.1136/bmj.c3493

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.

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.

2009-12-0179 citations

10.1097/aog.0b013e3181c2ca21

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.

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.

2009-04-01414 citations

10.1086/597307

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.

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.

2009-04-01189 citations

10.1086/597309

Prevalence of human papillomavirus types 6, 11, 16 and 18 in young Austrian women - baseline data of a phase III vaccine trial.

Six L, Leodolter S, Sings HL, Barr E, Haupt R, Joura EA.

2008-01-013 citations

10.1007/s00508-008-1093-3

Safety and immunogenicity of co-administered quadrivalent human papillomavirus (HPV)-6/11/16/18 L1 virus-like particle (VLP) and hepatitis B (HBV) vaccines.

Wheeler CM, Bautista OM, Tomassini JE, Nelson M, Sattler CA, Barr E, Protocol 11 study Investigators.

2007-12-0548 citations

10.1016/j.vaccine.2007.11.043

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.

Ault KA, Future II Study Group.

2007-06-01375 citations

10.1016/s0140-6736(07)60852-6

Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases.

Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, Tang GW, Ferris DG, Steben M, Bryan J, Taddeo FJ, Railkar R, Esser MT, Sings HL, Nelson M, Boslego J, Sattler C, Barr E, Koutsky LA, Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) I Investigators.

2007-05-011,224 citations

10.1056/nejmoa061760

Interventions

BIOLOGICALV501

Final Manufactured Product (FMP) quadrivalent HPV vaccine, a 0.5 mL intramuscular injection given at Day 1, Month 2 and Month 6.

BIOLOGICALComparator: Placebo

a 0.5 mL intramuscular placebo injection given at Day 1, Month 2 and Month 6.

BIOLOGICALHuman Papillomavirus (HPV) 16 Monovalent

HPV 16 Monovalent vaccine, a 0.5 mL intramuscular injection given at Day 1, Month 2 and Month 6.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

FEMALE

Age

16 Years to 23 Years

Healthy volunteers

Yes

Inclusion criteria

* Female with an intact uterus with lifetime history of 0-4 sexual partners

Exclusion criteria

* Prior Human Papillomavirus (HPV) vaccination * Prior abnormal paps * History of genital warts

Design outcomes

Primary

Measure	Time frame
Incidence of HPV 6/11/16/18-related Cervical Intraepithelial Neoplasia (CIN)(Any Grade), Adenocarcinoma In Situ (AIS) or Cervical Cancer	Follow-up through end of study (4 years)
Incidence of HPV 6/11/16/18-related External Genital Lesions (EGL) [Genital Warts, Vulvar/Vaginal Intraepithelial Neoplasia (Any Grade), Vulvar/Vaginal Cancer]	Follow-up through end of study (4 years)

Participant flow

Recruitment details

The study Protocol 013 (NCT00092521) (N =5759 total randomized) was comprised of two sub-studies: Protocol 011 (NCT00517309) (N=1877 total randomized) and Protocol 012 (NCT00092482) (N=3882 total randomized). Final safety data are presented in the results for Protocol 013 (NCT00092521): the final participant visit took place on 19 January 2009.

Participants by arm

Arm	Count
Group 1 - Base Study Quadrivalent Human Papillomavirus 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. The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the Quadrivalent HPV vaccine; from completion of the Vaccination Period at Month 7 through Month 48 of the study.	2,723
Group 2 - Base Study Monovalent HPV (Type 16) Vaccine 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 the Monovalent (HPV 16) HPV vaccine. The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the Monovalent (HPV 16) HPV vaccine; from completion of the Vaccination Period at Month 7 through Month 48 of the study.	304
Group 3 - Base Study Placebo The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 3 were vaccinated (at Day 1, Month 2 and Month 6) with placebo. The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received placebo; from completion of the Vaccination Period at Month 7 through Month 48 of the study.	2,732
Total	5,759

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Extension Study (Group 4)	Adverse Event	0	0	0	2
Extension Study (Group 4)	Excluded ineligible for extension	0	0	0	23
Extension Study (Group 4)	Lost to Follow-up	0	0	0	87
Extension Study (Group 4)	Moved	0	0	0	16
Extension Study (Group 4)	Pregnancy	0	0	0	4
Extension Study (Group 4)	Protocol Violation	0	0	0	2
Extension Study (Group 4)	Site Terminated	0	0	0	4
Extension Study (Group 4)	Unable/unwilling to return	0	0	0	25
Extension Study (Group 4)	Withdrawal by Subject	0	0	0	46
Follow-Up (After Month 7)	Adverse Event	1	0	0	0
Follow-Up (After Month 7)	Death	2	0	1	0
Follow-Up (After Month 7)	Lost to Follow-up	113	14	108	0
Follow-Up (After Month 7)	Moved	32	2	28	0
Follow-Up (After Month 7)	Protocol Violation	1	1	5	0
Follow-Up (After Month 7)	Site Terminated	3	0	3	0
Follow-Up (After Month 7)	Subjects Continuing	34	4	35	0
Follow-Up (After Month 7)	Subjects in Extension	13	109	412	0
Follow-Up (After Month 7)	Travel	2	0	0	0
Follow-Up (After Month 7)	Visits Compressed	5	0	5	0
Follow-Up (After Month 7)	Withdrawal by Subject	40	6	51	0
Vaccination (Day 1 Through Month 7)	Adverse Event	1	0	7	0
Vaccination (Day 1 Through Month 7)	Death	0	0	1	0
Vaccination (Day 1 Through Month 7)	Lost to Follow-up	51	6	44	0
Vaccination (Day 1 Through Month 7)	Moved	14	1	18	0
Vaccination (Day 1 Through Month 7)	New Medical History (Not AE)	2	0	0	0
Vaccination (Day 1 Through Month 7)	Pregnancy	5	0	7	0
Vaccination (Day 1 Through Month 7)	Randomized Not Vaccinated	6	0	7	0
Vaccination (Day 1 Through Month 7)	Unblinded	2	0	0	0
Vaccination (Day 1 Through Month 7)	Withdrawal by Subject	59	7	62	0

Baseline characteristics

Characteristic	Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine	Group 2 - Base Study Monovalent HPV (Type 16) Vaccine	Group 3 - Base Study Placebo	Total
Age, Continuous	20 Years	20 Years	20 Years	20 Years
Age, Customized 16 to 24 Years of Age	2723 Participants	304 Participants	2732 Participants	5759 Participants
Race/Ethnicity, Customized Asian	151 participants	27 participants	165 participants	343 participants
Race/Ethnicity, Customized Black	136 participants	5 participants	167 participants	308 participants
Race/Ethnicity, Customized Hispanic American	567 participants	93 participants	566 participants	1226 participants
Race/Ethnicity, Customized Native American	10 participants	2 participants	10 participants	22 participants
Race/Ethnicity, Customized Other - Unspecified	259 participants	6 participants	266 participants	531 participants
Race/Ethnicity, Customized White	1600 participants	171 participants	1558 participants	3329 participants
Sex: Female, Male Female	2723 Participants	304 Participants	2732 Participants	5759 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	2,458 / 2,673	276 / 299	2,331 / 2,672	0 / 0
serious Total, serious adverse events	50 / 2,673	4 / 299	45 / 2,672	5 / 801

Outcome results

Primary

Incidence of HPV 6/11/16/18-related Cervical Intraepithelial Neoplasia (CIN)(Any Grade), Adenocarcinoma In Situ (AIS) or Cervical Cancer

Time frame: Follow-up through end of study (4 years)

Population: Per-protocol population: subjects must have no major protocol violations, must be seronegative to the relevant type at Day 1 and Polymerase Chain Reaction (PCR) negative to the relevant type through Month 7, and must provide follow-up data. Group 2 Base Study Monovalent HPV Vaccine was not part of the pre-specified efficacy analysis population.

Arm	Measure	Value (NUMBER)
Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine	Incidence of HPV 6/11/16/18-related Cervical Intraepithelial Neoplasia (CIN)(Any Grade), Adenocarcinoma In Situ (AIS) or Cervical Cancer	0 incidence rate per 100 person-years
Group 3 - Base Study Placebo	Incidence of HPV 6/11/16/18-related Cervical Intraepithelial Neoplasia (CIN)(Any Grade), Adenocarcinoma In Situ (AIS) or Cervical Cancer	1.2 incidence rate per 100 person-years

95% CI: [95.1, 100]

Primary

Incidence of HPV 6/11/16/18-related External Genital Lesions (EGL) [Genital Warts, Vulvar/Vaginal Intraepithelial Neoplasia (Any Grade), Vulvar/Vaginal Cancer]

Time frame: Follow-up through end of study (4 years)

Population: Per-protocol population: subjects must have no major protocol violations, must be seronegative to the relevant type at Day 1 and PCR negative to the relevant type through Month 7, and must provide follow-up data.~Group 2 Base Study Monovalent HPV (Type 16) Vaccine was not part of the pre-specified efficacy analysis population.

Arm	Measure	Value (NUMBER)
Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine	Incidence of HPV 6/11/16/18-related External Genital Lesions (EGL) [Genital Warts, Vulvar/Vaginal Intraepithelial Neoplasia (Any Grade), Vulvar/Vaginal Cancer]	0 incidence rate per 100 person-years
Group 3 - Base Study Placebo	Incidence of HPV 6/11/16/18-related External Genital Lesions (EGL) [Genital Warts, Vulvar/Vaginal Intraepithelial Neoplasia (Any Grade), Vulvar/Vaginal Cancer]	1.1 incidence rate per 100 person-years

95% CI: [94.9, 100]

Cervical Intraepithelial Neoplasm (CIN)-Warts Efficacy Trial in Women (Gardasil)(V501-013)(COMPLETED)

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Participant flow

Recruitment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Incidence of HPV 6/11/16/18-related Cervical Intraepithelial Neoplasia (CIN)(Any Grade), Adenocarcinoma In Situ (AIS) or Cervical Cancer

Incidence of HPV 6/11/16/18-related External Genital Lesions (EGL) [Genital Warts, Vulvar/Vaginal Intraepithelial Neoplasia (Any Grade), Vulvar/Vaginal Cancer]