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
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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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
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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.
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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
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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
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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.

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.

Serious Adverse Events
    HPV 16 L1 VLP (Group 1)     Placebo (Group 2)     Extension  
Total, serious adverse events        
# participants affected / at risk     19/1191 (1.60%)     20/1196 (1.67%)     1/400 (0.25%)  
Cardiac disorders        
Pericarditis * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Gastrointestinal disorders        
Abdominal discomfort * 1      
# participants affected / at risk     1/1191 (0.08%)     1/1196 (0.08%)     0/400 (0.00%)  
Abdominal pain * 1      
# participants affected / at risk     1/1191 (0.08%)     0/1196 (0.00%)     0/400 (0.00%)  
Nausea * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Hepatobiliary disorders        
Cholecystitis * 1      
# participants affected / at risk     1/1191 (0.08%)     0/1196 (0.00%)     0/400 (0.00%)  
Infections and infestations        
Appendicitis * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Influenza * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Pneumonia * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Pyelonephritis * 1      
# participants affected / at risk     1/1191 (0.08%)     1/1196 (0.08%)     0/400 (0.00%)  
Pyelonephritis acute * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Injury, poisoning and procedural complications        
Accidental overdose * 1      
# participants affected / at risk     1/1191 (0.08%)     0/1196 (0.00%)     0/400 (0.00%)  
Alcohol poisoning * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Back injury * 1      
# participants affected / at risk     0/1191 (0.00%)     2/1196 (0.17%)     0/400 (0.00%)  
Humerus fracture * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Joint dislocation * 1      
# participants affected / at risk     1/1191 (0.08%)     1/1196 (0.08%)     0/400 (0.00%)  
Multiple injuries * 1      
# participants affected / at risk     1/1191 (0.08%)     0/1196 (0.00%)     0/400 (0.00%)  
Nerve injury * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Overdose * 1      
# participants affected / at risk     1/1191 (0.08%)     1/1196 (0.08%)     0/400 (0.00%)  
Pelvic fracture * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Radial nerve injury * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Road traffic accident * 1      
# participants affected / at risk     0/1191 (0.00%)     2/1196 (0.17%)     0/400 (0.00%)  
Urinary bladder rupture * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Metabolism and nutrition disorders        
Dehydration * 1      
# participants affected / at risk     1/1191 (0.08%)     0/1196 (0.00%)     0/400 (0.00%)  
Musculoskeletal and connective tissue disorders        
Arthropathy * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Intervertebral disc protrusion * 1      
# participants affected / at risk     1/1191 (0.08%)     0/1196 (0.00%)     0/400 (0.00%)  
Limb deformity * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Nervous system disorders        
Headache * 1      
# participants affected / at risk     0/1191 (0.00%)     0/1196 (0.00%)     1/400 (0.25%)  
Syncope * 1      
# participants affected / at risk     1/1191 (0.08%)     0/1196 (0.00%)     0/400 (0.00%)  
Pregnancy, puerperium and perinatal conditions        
Ectopic pregnancy * 1      
# participants affected / at risk     1/1191 (0.08%)     0/1196 (0.00%)     0/400 (0.00%)  
Psychiatric disorders        
Aggression * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Anxiety disorder * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Bulimia nervosa * 1      
# participants affected / at risk     1/1191 (0.08%)     0/1196 (0.00%)     0/400 (0.00%)  
Completed suicide * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Depression * 1      
# participants affected / at risk     0/1191 (0.00%)     2/1196 (0.17%)     0/400 (0.00%)  
Mania * 1      
# participants affected / at risk     0/1191 (0.00%)     1/1196 (0.08%)     0/400 (0.00%)  
Suicide attempt * 1      
# participants affected / at risk     0/1191 (0.00%)     2/1196 (0.17%)     0/400 (0.00%)  
Reproductive system and breast disorders        
Perineal laceration * 1      
# participants affected / at risk     1/1191 (0.08%)     0/1196 (0.00%)     0/400 (0.00%)  
Dysfunctional uterine bleeding * 1      
# participants affected / at risk     1/1191 (0.08%)     0/1196 (0.00%)     0/400 (0.00%)  
Ovarian cyst * 1      
# participants affected / at risk     1/1191 (0.08%)     0/1196 (0.00%)     0/400 (0.00%)  
Ovarian cyst ruptured * 1      
# participants affected / at risk     1/1191 (0.08%)     1/1196 (0.08%)     0/400 (0.00%)  
Respiratory, thoracic and mediastinal disorders        
Asthma * 1      
# participants affected / at risk     2/1191 (0.17%)     1/1196 (0.08%)     0/400 (0.00%)  
Vascular disorders        
Haemorrhage * 1      
# participants affected / at risk     1/1191 (0.08%)     1/1196 (0.08%)     0/400 (0.00%)  
Thrombosis * 1      
# participants affected / at risk     1/1191 (0.08%)     0/1196 (0.00%)     0/400 (0.00%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 12.0




  Other Adverse Events


  Limitations and Caveats
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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.


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