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Efficacy and Tolerability Study of V501 in Japanese Males (V501-122)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01862874
Recruitment Status : Completed
First Posted : May 27, 2013
Results First Posted : August 31, 2018
Last Update Posted : April 2, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Anogenital Human Papilloma Virus Infection
Condyloma Acuminata
Interventions Biological: V501
Biological: Placebo
Enrollment 1124
Recruitment Details A total of 1129 participants were screened and 1124 were randomized.
Pre-assignment Details  
Arm/Group Title V501 Placebo
Hide Arm/Group Description Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36. Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Period Title: Overall Study
Started 562 [1] 562 [1]
Vaccination 1 561 562
Vaccination 2 539 542
Vaccination 3 530 532
Completed 483 485
Not Completed 79 77
Reason Not Completed
Randomized not treated             1             0
Adverse Event             0             3
Lost to Follow-up             26             29
Physician Decision             5             3
Withdrawn by parent/guardian             1             1
Withdrawal by Subject             46             40
Death             0             1
[1]
Randomized participants
Arm/Group Title V501 Placebo Total
Hide Arm/Group Description Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36. Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36. Total of all reporting groups
Overall Number of Baseline Participants 562 562 1124
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 562 participants 562 participants 1124 participants
22.6  (2.1) 22.6  (2.0) 22.6  (2.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 562 participants 562 participants 1124 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
562
 100.0%
562
 100.0%
1124
 100.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 562 participants 562 participants 1124 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
562
 100.0%
562
 100.0%
1124
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Combined Incidence of HPV Type 6, 11, 16, or 18-related Persistent Infection
Hide Description Persistent infection was defined as 1) polymerase chain reaction (PCR) positive to HPV Type 6, 11, 16, or 18 in 2 consecutive anogenital or biopsy samples collected ≥4 months apart, or 2) Pathology Panel consensus diagnosis of condyloma acuminate, penile/perianal/perineal intraepithelial neoplasia (PIN), penile, perianal, or perineal cancer and PCR detection of HPV Type 6, 11, 16, or 18 in an adjacent section and PCR positive for the same HPV type at a separate adjacent visit. The combined incidence of HPV Type 6, 11, 16, or 18 persistent infection detected in samples from ≥2 consecutive visits ≥6 months apart was assessed.
Time Frame Up to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were seronegative at Day 1 and PCR negative from Day 1 through Month 7 to the relevant HPV type, received all 3 vaccinations, did not deviate from the study protocol in ways that might interfere with vaccine efficacy, and had ≥1 follow-up visit after Month 7.
Arm/Group Title V501 Placebo
Hide Arm/Group Description:
Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Overall Number of Participants Analyzed 497 498
Overall Number of Units Analyzed
Type of Units Analyzed: Person-years follow-up
1137 1123
Measure Type: Number
Unit of Measure: Cases per 100 person-years of follow-up
0.3 1.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection V501, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method One-sided exact test
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Efficacy
Estimated Value 85.9
Confidence Interval (2-Sided) 95%
52.7 to 97.3
Estimation Comments Vaccine efficacy is defined as the percentage reduction in relative risk for the V501 group versus the placebo group.
Other Statistical Analysis If the lower bound of the 95% confidence interval for vaccine efficacy excludes 0%, then superiority of the V501 group is demonstrated.
2.Primary Outcome
Title Percentage of Participants With Maximum Temperature ≥37.5°C Reported on the Vaccination Report Card
Hide Description Body temperature (oral or oral equivalent) was recorded on the Vaccination Report Card (VRC). The percentage of participants with a maximum temperature ≥37.5°C was summarized.
Time Frame Up to 5 days after any vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received ≥1 study vaccination and had follow-up data available.
Arm/Group Title V501 Placebo
Hide Arm/Group Description:
Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Overall Number of Participants Analyzed 551 557
Measure Type: Number
Unit of Measure: Percentage of participants
2.7 3.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection V501, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Statistical testing of no difference in incidence of maximum temperature ≥37.5°C
Statistical Test of Hypothesis P-Value 0.256
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-3.5 to 0.9
Estimation Comments Risk difference (V501 - placebo) was estimated using the Miettinen & Nurminen method.
3.Primary Outcome
Title Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card
Hide Description An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study drug. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug or a protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study drug or protocol-specified procedure is also an AE. The percentage of participants with an injection-site AE prompted on the VRC (erythema, pain, and swelling) was summarized.
Time Frame Up to 5 days after any vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received ≥1 study vaccination and had follow-up data available.
Arm/Group Title V501 Placebo
Hide Arm/Group Description:
Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Overall Number of Participants Analyzed 554 559
Measure Type: Number
Unit of Measure: Percentage of participants
Injection-site erythema 24.5 21.6
Injection-site pain 54.9 48.5
Injection-site swelling 21.3 14.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection V501, Placebo
Comments Injection-site erythema
Type of Statistical Test Other
Comments Statistical testing of no difference in incidence of injection-site erythema
Statistical Test of Hypothesis P-Value 0.251
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 2.9
Confidence Interval (2-Sided) 95%
-2.1 to 7.9
Estimation Comments Risk difference (V501 - placebo) was estimated using the Miettinen & Nurminen method.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection V501, Placebo
Comments Injection-site pain
Type of Statistical Test Other
Comments Statistical testing of no difference in incidence of injection-site pain
Statistical Test of Hypothesis P-Value 0.033
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 6.4
Confidence Interval (2-Sided) 95%
0.5 to 12.2
Estimation Comments Risk difference (V501 - placebo) was estimated using the Miettinen & Nurminen method.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection V501, Placebo
Comments Injection-site swelling
Type of Statistical Test Other
Comments Statistical testing of no difference in incidence of injection-site swelling
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 6.8
Confidence Interval (2-Sided) 95%
2.3 to 11.3
Estimation Comments Risk difference (V501 - placebo) was estimated using the Miettinen & Nurminen method.
4.Primary Outcome
Title Percentage of Participants With a Systemic Adverse Event
Hide Description An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study drug. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug or a protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study drug or protocol-specified procedure is also an AE. The percentage of participants with a systemic AE was summarized.
Time Frame Up to 15 days after any vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received ≥1 study vaccination and had follow-up data available.
Arm/Group Title V501 Placebo
Hide Arm/Group Description:
Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Overall Number of Participants Analyzed 554 559
Measure Type: Number
Unit of Measure: Percentage of participants
14.4 15.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection V501, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Statistical testing of no difference in incidence of systemic AEs
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-5.2 to 3.3
Estimation Comments Risk difference (V501 - placebo) was estimated using the Miettinen & Nurminen method.
5.Primary Outcome
Title Percentage of Participants With a Vaccine-related Systemic Adverse Event
Hide Description An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study drug. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug or a protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study drug or protocol-specified procedure is also an AE. Vaccine-related AEs are those that were deemed possibly, probably, or definitely related to vaccine administration by the investigator. The percentage of participants with a vaccine-related systemic AE was summarized.
Time Frame Up to 15 days after any vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received ≥1 study vaccination and had follow-up data available.
Arm/Group Title V501 Placebo
Hide Arm/Group Description:
Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Overall Number of Participants Analyzed 554 559
Measure Type: Number
Unit of Measure: Percentage of participants
3.4 5.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection V501, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Statistical testing of no difference in incidence of vaccine-related systemic AEs
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-4.1 to 0.8
Estimation Comments Risk difference (V501 - placebo) was estimated using the Miettinen & Nurminen method.
6.Secondary Outcome
Title Combined Incidence of HPV Type 6, 11, 16, or 18-related Persistent Infection or Disease
Hide Description Persistent infection was defined as 1) polymerase chain reaction (PCR) positive to HPV Type 6, 11, 16, or 18 in 2 consecutive anogenital or biopsy samples collected ≥4 months apart, or 2) Pathology Panel consensus diagnosis of condyloma acuminate, penile/perianal/perineal intraepithelial neoplasia (PIN), penile, perianal, or perineal cancer and PCR detection of HPV Type 6, 11, 16, or 18 in an adjacent section and PCR positive for the same HPV type at a separate adjacent visit. The incidence of persistent infection detected in samples from ≥2 consecutive visits ≥6 months apart was assessed. Disease was defined as HPV Type 6, 11, 16, or 18-related condyloma acuminate, PIN, penile, perianal, or perineal cancer. The combined incidence of HPV Type 6, 11, 16, or 18 persistent infection or disease was assessed.
Time Frame Up to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were seronegative at Day 1 and PCR negative from Day 1 through Month 7 to the relevant HPV type, received all 3 vaccinations, did not deviate from the study protocol in ways that might interfere with vaccine efficacy, and had ≥1 follow-up visit after Month 7.
Arm/Group Title V501 Placebo
Hide Arm/Group Description:
Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
Overall Number of Participants Analyzed 498 498
Overall Number of Units Analyzed
Type of Units Analyzed: Person-years follow-up
1148 1132
Measure Type: Number
Unit of Measure: Cases per 100 person-years at risk
0.3 1.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection V501, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method One-sided exact test
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Efficacy
Estimated Value 86.5
Confidence Interval (2-Sided) 95%
55.2 to 97.4
Estimation Comments Vaccine efficacy is defined as the percentage reduction in relative risk for the V501 versus the placebo group.
Other Statistical Analysis If the lower bound of the 95% confidence interval for vaccine efficacy excludes 0%, superiority of the V501 group is demonstrated.
Time Frame Up to 36 months
Adverse Event Reporting Description The at-risk population was participants who received ≥1 study vaccination and had follow-up data available
 
Arm/Group Title V501 Placebo
Hide Arm/Group Description Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36. Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.
All-Cause Mortality
V501 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/554 (0.00%)      1/559 (0.18%)    
Hide Serious Adverse Events
V501 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/554 (0.00%)      1/559 (0.18%)    
Psychiatric disorders     
Completed suicide  1  0/554 (0.00%)  0 1/559 (0.18%)  1
1
Term from vocabulary, MedDRA version 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
V501 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   329/554 (59.39%)      303/559 (54.20%)    
General disorders     
Injection-site erythema  1  137/554 (24.73%)  217 122/559 (21.82%)  179
Injection-site pain  1  304/554 (54.87%)  563 271/559 (48.48%)  480
Injection-site swelling  1  118/554 (21.30%)  181 82/559 (14.67%)  121
1
Term from vocabulary, MedDRA version 20.1
Indicates events were collected by systematic assessment
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.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01862874    
Other Study ID Numbers: V501-122
132237 ( Registry Identifier: JAPIC-CTI )
2015-002931-16 ( EudraCT Number )
V501-122 ( Other Identifier: Merck Protocol Number )
First Submitted: May 22, 2013
First Posted: May 27, 2013
Results First Submitted: July 30, 2018
Results First Posted: August 31, 2018
Last Update Posted: April 2, 2019