Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

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: October 22, 2015
Last verified: October 2015
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 
Overall Participants Analyzed 
[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 ]

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
  Hide Other Adverse Events

Time Frame Adverse events (AEs) were collected from Day 1 until Month 7. No non-serious AEs were collected and no Vaccination Report Card (VRCs) were used in the extension study, therefore no data is entered for that group in the Other Adverse Events table.
Additional Description Subjects were observed for at least 20 minutes after each vaccination for any immediate reaction. Subjects were prompted to report temperatures and local (i.e., injection site) AEs for 5 days following each injection. Data on all other AEs were collected and recorded on the subject’s vaccine report card for 14 days after each vaccination visit.

Frequency Threshold
Threshold above which other adverse events are reported   5  

Reporting Groups
  Description
HPV 16 L1 VLP (Group 1) The number of subjects who actually received the vaccine material corresponding to the indicated vaccination group. There was one subject randomized to the HPV 16 L1 VLP vaccine group who received placebo and then discontinued study participation. There was 1 subject randomized to the placebo group who received one vaccination of HPV 16 L1 VLP vaccine and then discontinued study participation. These 2 subjects were included in the counts reported in the Adverse Event tables. There were 2 subjects randomized to the HPV 16 L1 VLP vaccine group and 2 subjects randomized to the placebo group and who received mixed vaccine material. These 4 subjects were not included in the counts reported in this table. Therefore, this table reports N=1191 (1193 minus 2) subjects vaccinated with HPV 16 L1 VLP vaccine and N=1196 (1198 minus 2) subjects vaccinated with placebo.
Placebo (Group 2) The number of subjects who actually received the vaccine material corresponding to the indicated vaccination group. There was one subject randomized to the HPV 16 L1 VLP vaccine group who received placebo and then discontinued study participation. There was 1 subject randomized to the placebo group who received one vaccination of HPV 16 L1 VLP vaccine and then discontinued study participation. These 2 subjects were included in the counts reported in the Adverse Event tables. There were 2 subjects randomized to the HPV 16 L1 VLP vaccine group and 2 subjects randomized to the placebo group and who received mixed vaccine material. These 4 subjects were not included in the counts reported in this table. Therefore, this table reports N=1191 (1193 minus 2) subjects vaccinated with HPV 16 L1 VLP vaccine and N=1196 (1198 minus 2) subjects vaccinated with placebo.
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.

Other Adverse Events
    HPV 16 L1 VLP (Group 1)   Placebo (Group 2)   Extension
Total, other (not including serious) adverse events       
# participants affected / at risk   1025/1191 (86.06%)   1013/1196 (84.70%)   0/0 
Gastrointestinal disorders       
Nausea * 1       
# participants affected / at risk   91/1191 (7.64%)   95/1196 (7.94%)   0/0 
General disorders       
Fatigue * 1       
# participants affected / at risk   59/1191 (4.95%)   64/1196 (5.35%)   0/0 
Injection Site Erythema * 1       
# participants affected / at risk   335/1191 (28.13%)   286/1196 (23.91%)   0/0 
Injection Site Haematoma * 1       
# participants affected / at risk   69/1191 (5.79%)   61/1196 (5.10%)   0/0 
Injection Site Pain * 1       
# participants affected / at risk   951/1191 (79.85%)   924/1196 (77.26%)   0/0 
Injection Site Swelling * 1       
# participants affected / at risk   288/1191 (24.18%)   211/1196 (17.64%)   0/0 
Infections and infestations       
Nasopharyngitis * 1       
# participants affected / at risk   85/1191 (7.14%)   88/1196 (7.36%)   0/0 
Nervous system disorders       
Dizziness * 1       
# participants affected / at risk   53/1191 (4.45%)   62/1196 (5.18%)   0/0 
Headache * 1       
# participants affected / at risk   499/1191 (41.90%)   495/1196 (41.39%)   0/0 
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain * 1       
# participants affected / at risk   68/1191 (5.71%)   65/1196 (5.43%)   0/0 
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 12.0



  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