Human Papillomavirus (HPV) Registration Study (Gardasil)(V501-023)(COMPLETED)

• ClinicalTrials.gov Identifier: NCT00157950
• Recruitment Status: Completed
• First Posted: September 12, 2005
• Results First Posted: September 14, 2010
• Last Update Posted: February 4, 2016
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Papillomavirus Infections
• Interventions: Biological: Gardasil™; Biological: Placebo
• Enrollment: 176

Participant Flow

Recruitment Details	Patients were recruited at 10 medical sites in Korea. First Patient Treated: 20-Oct-2005 Last Patient Treated: 24-Jun-2006
Pre-assignment Details	A serum or urine pregnancy test was performed prior to each injection on all subjects. Results were available prior to vaccination. Any subject with a positive pregnancy test at Day 1 was not randomized or vaccinated, and was not eligible to continue in the study.

Arm/Group Title	Gardasil™	Placebo
Arm/Group Description	Gardasil™ 3 dose regimen (Day 1, Month 2 and Month 6)	Gardasil™ matching placebo 3 dose regimen (Day 1, Month 2 and Month 6)
Period Title: Overall Study
Started	117	59
Vaccinated at Dose 1	117	59
Vaccinated at Dose 2	117	59
Vaccinated at Dose 3	116	59
Completed	116	59
Not Completed	1	0
Reason Not Completed
Death	1	0

Baseline Characteristics

Arm/Group Title		Gardasil™	Placebo	Total
Arm/Group Description		Gardasil™ 3 dose regimen (Day 1, Month 2 and Month 6)	Gardasil™ matching placebo 3 dose regimen (Day 1, Month 2 and Month 6)	Total of all reporting groups
Overall Number of Baseline Participants		117	59	176
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	117 participants	59 participants	176 participants
		16.7 (4.9)	16.5 (5.2)	16.6 (5.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	117 participants	59 participants	176 participants
	Female	117 100.0%	59 100.0%	176 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	117 participants	59 participants	176 participants
		117	59	176

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Seroconvert to HPV 6.
Description	Vaccine-induced anti-HPV 6 seroconversion following administration of a 3-dose regimen of GARDASIL® in females 9 to 23 years of age in Korea. Seroconversion for HPV 6 was defined as achieving an anti-HPV cLIA (Competitive Luminex immunoassay) level of at least 20 mMU/mL.
Time Frame	Week 4 Postdose 3

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.

Arm/Group Title	Gardasil™	Placebo
Arm/Group Description:	Gardasil™ 3 dose regimen (Day 1, Month 2 and Month 6)	Gardasil™ matching placebo 3 dose regimen (Day 1, Month 2 and Month 6)
Overall Number of Participants Analyzed	111	58
Measure Type: Number; Unit of Measure: Participants
	109	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gardasil™
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	98.2
	Confidence Interval	(2-Sided) 95%; 93.6 to 99.8
	Estimation Comments	Exact binomial confidence interval

2. Primary Outcome

Title	Number of Participants Who Seroconvert to HPV 11.
Description	Vaccine-induced anti-HPV 11 seroconversion following administration of a 3-dose regimen of GARDASIL® in females 9 to 23 years of age in Korea. Seroconversion for HPV 11 was defined as achieving an anti-HPV cLIA (Competitive Luminex immunoassay) level of at least 16 mMU/mL.
Time Frame	Week 4 Postdose 3

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.

Arm/Group Title	Gardasil™	Placebo
Arm/Group Description:	Gardasil™ 3 dose regimen (Day 1, Month 2 and Month 6)	Gardasil™ matching placebo 3 dose regimen (Day 1, Month 2 and Month 6)
Overall Number of Participants Analyzed	112	58
Measure Type: Number; Unit of Measure: Participants
	112	1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gardasil™
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The lower bound of the 95% confidence interval for the proportion of subjects receiving Gardasil who were seropositive at Week 4 postdose 3 must be greater than 90%
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	100
	Confidence Interval	(2-Sided) 95%; 96.8 to 100
	Estimation Comments	Exact binomial confidence interval

3. Primary Outcome

Title	Number of Participants Who Seroconvert to HPV 16.
Description	Vaccine-induced anti-HPV 16 seroconversion following administration of a 3-dose regimen of GARDASIL® in females 9 to 23 years of age in Korea. Seroconversion for HPV 16 was defined as achieving an anti-HPV cLIA (Competitive Luminex immunoassay) level of at least 20 mMU/mL.
Time Frame	Week 4 Postdose 3

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.

Arm/Group Title	Gardasil™	Placebo
Arm/Group Description:	Gardasil™ 3 dose regimen (Day 1, Month 2 and Month 6)	Gardasil™ matching placebo 3 dose regimen (Day 1, Month 2 and Month 6)
Overall Number of Participants Analyzed	113	58
Measure Type: Number; Unit of Measure: Participants
	112	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gardasil™
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The lower bound of the 95% confidence interval for the proportion of subjects receiving Gardasil who were seropositive at Week 4 postdose 3 must be greater than 90%
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	99.1
	Confidence Interval	(2-Sided) 95%; 95.2 to 100
	Estimation Comments	Exact binomial confidence interval

4. Primary Outcome

Title	Number of Participants Who Seroconvert to HPV 18.
Description	Vaccine-induced anti-HPV 18 seroconversion following administration of a 3-dose regimen of GARDASIL® in females 9 to 23 years of age in Korea. Seroconversion for HPV 18 was defined as achieving an anti-HPV cLIA (Competitive Luminex immunoassay) level of at least 24 mMU/mL.
Time Frame	Week 4 Postdose 3

Outcome Measure Data

Analysis Population Description

Per-protocol population: subjects must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data.

Arm/Group Title	Gardasil™	Placebo
Arm/Group Description:	Gardasil™ 3 dose regimen (Day 1, Month 2 and Month 6)	Gardasil™ matching placebo 3 dose regimen (Day 1, Month 2 and Month 6)
Overall Number of Participants Analyzed	110	58
Measure Type: Number; Unit of Measure: Participants
	109	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gardasil™
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The lower bound of the 95% confidence interval for the proportion of subjects receiving Gardasil who were seropositive at Week 4 postdose 3 must be greater than 90%
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	99.1
	Confidence Interval	(2-Sided) 95%; 95.0 to 100
	Estimation Comments	Exact binomial confidence interval

5. Secondary Outcome

Title	Number of Participants With Adverse Experiences
Description	Number of participants who reported 1 or more adverse experience.
Time Frame	Overall study including 14 calendar days after the last vaccination visit.

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of injection.

Arm/Group Title	Gardasil™	Placebo
Arm/Group Description:	Gardasil™ 3 dose regimen (Day 1, Month 2 and Month 6)	Gardasil™ matching placebo 3 dose regimen (Day 1, Month 2 and Month 6)
Overall Number of Participants Analyzed	117	59
Measure Type: Number; Unit of Measure: Participants
Discontinued due to an Adverse Experience (AE)	0	0
Discontinued due to vaccine related AE	0	0
Discontinued due to an Serious AE	0	0
Discontinued due to serious vaccine-related AE	0	0

Adverse Events

Time Frame	During the double-blind period including 14 calendar days after the last vaccination visit.
Adverse Event Reporting Description	Although a participant may have had two or more adverse experiences the participant is counted only once in a category. The same participant may appear in different categories.
Arm/Group Title	Gardasil™	Placebo
Arm/Group Description	Gardasil™ 3 dose regimen (Day 1, Month 2 and Month 6)	Gardasil™ matching placebo 3 dose regimen (Day 1, Month 2 and Month 6)
All-Cause Mortality
	Gardasil™	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Gardasil™	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/117 (0.85%)	1/59 (1.69%)
Infections and infestations
Acute pharyngitis * 1	0/117 (0.00%)	1/59 (1.69%)
Injury, poisoning and procedural complications
Traffic accident * 1	1/117 (0.85%)	0/59 (0.00%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (9.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Gardasil™	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	88/117 (75.21%)	41/59 (69.49%)
General disorders
Injection site erythema * 1	27/117 (23.08%)	4/59 (6.78%)
Injection site pain * 1	85/117 (72.65%)	30/59 (50.85%)
Injection site swelling * 1	33/117 (28.21%)	7/59 (11.86%)
Injection site tenderness * 1	2/117 (1.71%)	3/59 (5.08%)
Fever * 1	16/117 (13.68%)	10/59 (16.95%)
Infections and infestations
Cold * 1	10/117 (8.55%)	10/59 (16.95%)
Nervous system disorders
Headache * 1	5/117 (4.27%)	5/59 (8.47%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (9.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

• Name/Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.
• Phone: 1-800-672-6372
• EMail: ClinicalTrialsDisclosure@merck.com

Publications:

Kang S, Kim KH, Kim YT, Kim YT, Kim JH, Song YS, Shin SH, Ryu HS, Han JW, Kang JH, Park SY. Safety and immunogenicity of a vaccine targeting human papillomavirus types 6, 11, 16 and 18: a randomized, placebo-controlled trial in 176 Korean subjects. Int J Gynecol Cancer. 2008 Sep-Oct;18(5):1013-9. doi: 10.1111/j.1525-1438.2007.01123.x. Epub 2007 Nov 6.

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

Hurt L, Nsouli-Maktabi H, Rohrbeck P, Clark LL. Use of quadrivalent human papillomavirus vaccine and the prevalence of antibodies to vaccine-targeted strains among female service members before and after vaccination. MSMR. 2016 Feb;23(2):6-13.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00157950
• Other Study ID Numbers: V501-023; 2005_066
• First Submitted: September 7, 2005
• First Posted: September 12, 2005
• Results First Submitted: August 17, 2010
• Results First Posted: September 14, 2010
• Last Update Posted: February 4, 2016