Study of Human Papillomavirus (HPV) 16 Vaccine in the Prevention of HPV 16 Infection in 16- to 23-Year-Old Females (V501-005)(COMPLETED)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00365378
First received: August 16, 2006
Last updated: May 5, 2014
Last verified: May 2014
Results First Received: March 22, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Condition: HPV 16 Infection
Interventions: Biological: Comparator: HPV 16 L1 Vaccine
Biological: Comparator: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
HPV 16 L1 VLP (Group 1)

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 HPV (Human Papillomavirus) 16 Virus-Like Particle (VLP) Vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine from completion of the Vaccination Period at Month 7 through Month 48. (The Month 7 visit was to be scheduled to occur no earlier than 3 weeks and no later than 7 weeks following the Month 6 visit.)

Placebo (Group 2)

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.

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. (The Month 7 visit was to be scheduled to occur no earlier than 3 weeks and no later than 7 weeks following the Month 6 visit.)

Extension This group includes 400 subjects who received Monovalent HPV 16 L1 VLP vaccine or placebo during the base study. This includes subjects who previously discontinued from the study.

Participant Flow for 3 periods

Period 1:   Vaccination (Day 1 to Month 7)
    HPV 16 L1 VLP (Group 1)     Placebo (Group 2)     Extension  
STARTED     1204     1205     0  
Entered Vaccination Period     1193     1198     0  
COMPLETED     993     1038     0  
NOT COMPLETED     211     167     0  
Randomized Not Vaccinated                 11                 7                 0  
Adverse Event                 4                 5                 0  
Lost to Follow-up                 88                 75                 0  
Pregnancy                 19                 14                 0  
Protocol Violation                 22                 13                 0  
Withdrawal by Subject                 50                 44                 0  
Unspecified                 17                 9                 0  

Period 2:   Follow-up (Month 7 Though Month 48)
    HPV 16 L1 VLP (Group 1)     Placebo (Group 2)     Extension  
STARTED     993     1038     0  
COMPLETED     835     836     0  
NOT COMPLETED     158     202     0  
Moved                 6                 5                 0  
Lost to Follow-up                 67                 69                 0  
Pregnancy                 0                 1                 0  
Protocol Violation                 1                 2                 0  
Withdrawal by Subject                 73                 104                 0  
Unspecified                 11                 21                 0  

Period 3:   Extension
    HPV 16 L1 VLP (Group 1)     Placebo (Group 2)     Extension  
STARTED     0     0     400  
COMPLETED     0     0     203  
NOT COMPLETED     0     0     197  
Adverse Event                 0                 0                 1  
Moved                 0                 0                 8  
Lost to Follow-up                 0                 0                 57  
Protocol Violation                 0                 0                 2  
Withdrawal by Subject                 0                 0                 98  
Unspecified                 0                 0                 31  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
HPV 16 L1 VLP (Group 1)

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 HPV (Human Papillomavirus) 16 Virus-Like Particle (VLP) Vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine from completion of the Vaccination Period at Month 7 through Month 48.

Placebo (Group 2)

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.

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.

Total Total of all reporting groups

Baseline Measures
    HPV 16 L1 VLP (Group 1)     Placebo (Group 2)     Total  
Number of Participants  
[units: participants]
  1204     1205     2409  
Age  
[units: years]
Mean ( Full Range )
  20.0  
  ( 16 to 25 )  
  20.1  
  ( 16 to 23 )  
  20.1  
  ( 16 to 25 )  
Gender  
[units: participants]
     
Female     1204     1205     2409  
Male     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
     
Asian     69     73     142  
Black     94     114     208  
Hispanic American     89     93     182  
Native American     9     14     23  
White     918     889     1807  
Other     25     22     47  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Incidence of Persistent HPV 16 Infection   [ Time Frame: Through Month 48 ]
  Hide Outcome Measure 1

Measure Type Primary
Measure Title Incidence of Persistent HPV 16 Infection
Measure Description Cases of persistent infection were those with detection of HPV 16 by PCR (Polymerase chain reaction) on at least 2 consecutive visits at least 4 months apart; or detection of HPV 16 in a cervical biopsy specimen showing pathologic evidence of CIN1 (Cervical intraepithelial neoplasia), CIN2 or CIN3 together with HPV 16 detected at the visit immediately before or after the biopsy; or detection of HPV 16 on a subject's last visit.
Time Frame Through Month 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per-protocol population: subjects must have no major protocol violations, must be seronegative to HPV 16 at Day 1 and PCR (Polymerase chain reaction) negative to HPV 16 through Month 7, and must provide follow-up data after Month 7

Reporting Groups
  Description
HPV 16 L1 VLP (Group 1)

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 HPV (Human Papillomavirus) 16 Virus-Like Particle (VLP) Vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine from completion of the Vaccination Period at Month 7 through Month 48.

Placebo (Group 2)

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.

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.


Measured Values
    HPV 16 L1 VLP (Group 1)     Placebo (Group 2)  
Number of Participants Analyzed  
[units: participants]
  755     750  
Incidence of Persistent HPV 16 Infection  
[units: Incidence per 100 person-years]
  0.3     4.9  


Statistical Analysis 1 for Incidence of Persistent HPV 16 Infection
Groups [1] All groups
Vaccine Efficacy [2] 94.3
95% Confidence Interval ( 87.8 to 97.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
 

Vaccine Efficacy (% relative risk reduction)

Confidence Interval based on binomial tail probabilities and not from a dispersion parameter.




2.  Primary:   Incidence of HPV 16-related CIN1, CIN2 or C1N3   [ Time Frame: Through Month 48 ]

3.  Primary:   Serum Anti-HPV 16 Geometric Mean Titers   [ Time Frame: Month 7 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Of note, the number of subjects reported in the results posting is slightly different than that specified in the publication by Koutsky, et al (2002). The data provided here is based on final data.


  More Information