Cervical Intraepithelial Neoplasm (CIN)-Warts Efficacy Trial in Women (Gardasil)(V501-013)(COMPLETED)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00092521
First received: September 23, 2004
Last updated: November 27, 2013
Last verified: November 2013
Results First Received: August 3, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Conditions: Cervical Cancer
Genital Warts
Interventions: Biological: V501
Biological: Comparator: Placebo
Biological: Human Papillomavirus (HPV) 16 Monovalent

  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
The study Protocol 013 (NCT00092521) (N =5759 total randomized) was compromised of two sub-studies: Protocol 011 (NCT00517309) (N=1877 total randomized) and Protocol 012 (NCT00092482) (N=3882 total randomized). Final safety data are presented in the results for Protocol 013 (NCT00092521).

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
Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine

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 the Quadrivalent Human papillomavirus (HPV) vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the Quadrivalent HPV vaccine; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Group 2 - Base Study Monovalent HPV (Type 16) Vaccine

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 the Monovalent (HPV 16) HPV vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the Monovalent (HPV 16) HPV vaccine; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Group 2 Base Study Monovalent HPV (Type 16) Vaccine was not part of the pre-specified efficacy analysis population.

Group 3 - Base Study Placebo

The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 3 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 of the study.

Group 4 - Quadrivalent Human Papillomavirus Vaccine Extension This group includes 844 subjects who entered the extension including subjects who in the base study received fewer than the full three doses of Quadrivalent HPV vaccine during the base study (i.e., subjects who received placebo in the base study; subjects who received monovalent [type 16] HPV vaccine in the base study, or subjects who received ≥ 2 doses of quadrivalent HPV vaccine in the base study). Subjects who discontinued the base portion of the study could enter the extension portion of the study. In the extension period subjects designated as "Completed Period" are those who received three doses of quadrivalent HPV vaccine and completed all required follow-up visits. Subjects designated as "Not Completed" are those who: a) Received all three vaccinations, but did not complete follow-up; b) Did not receive all vaccinations, but completed follow-up, or c) Did not receive all vaccinations, and did not complete follow-up).

Participant Flow for 3 periods

Period 1:   Vaccination (Day 1 Through Month 7)
    Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine     Group 2 - Base Study Monovalent HPV (Type 16) Vaccine     Group 3 - Base Study Placebo     Group 4 - Quadrivalent Human Papillomavirus Vaccine Extension  
STARTED     2723     304     2732     0  
COMPLETED     2582     290     2587     0  
NOT COMPLETED     141     14     145     0  
Randomized Not Vaccinated                 6                 0                 7                 0  
Adverse Event                 1                 0                 7                 0  
Death                 1                 0                 0                 0  
Lost to Follow-up                 51                 6                 44                 0  
Pregnancy                 5                 0                 7                 0  
Withdrawal by Subject                 59                 7                 62                 0  
Moved                 14                 1                 18                 0  
Unblinded                 2                 0                 0                 0  
New Medical History (Not AE)                 2                 0                 0                 0  

Period 2:   Follow-Up (After Month 7)
    Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine     Group 2 - Base Study Monovalent HPV (Type 16) Vaccine     Group 3 - Base Study Placebo     Group 4 - Quadrivalent Human Papillomavirus Vaccine Extension  
STARTED     2599 [1]   291 [1]   2607 [1]   0  
COMPLETED     2354     155     1959     0  
NOT COMPLETED     245     136     648     0  
Subjects Continuing                 34                 4                 35                 0  
Subjects in Extension                 13                 109                 412                 0  
Adverse Event                 1                 0                 0                 0  
Death                 1                 0                 1                 0  
Lost to Follow-up                 113                 14                 108                 0  
Protocol Violation                 1                 1                 5                 0  
Withdrawal by Subject                 40                 6                 51                 0  
Moved                 32                 2                 28                 0  
Site Terminated                 3                 0                 3                 0  
Travel                 2                 0                 0                 0  
Visits Compressed                 5                 0                 5                 0  
[1] Includes subjects who did not receive 3 doses of vaccine/placebo but continued into the follow-up

Period 3:   Extension Study (Group 4)
    Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine     Group 2 - Base Study Monovalent HPV (Type 16) Vaccine     Group 3 - Base Study Placebo     Group 4 - Quadrivalent Human Papillomavirus Vaccine Extension  
STARTED     0     0     0     844  
COMPLETED     0     0     0     635  
NOT COMPLETED     0     0     0     209  
Excluded ineligible for extension                 0                 0                 0                 23  
Adverse Event                 0                 0                 0                 2  
Lost to Follow-up                 0                 0                 0                 87  
Pregnancy                 0                 0                 0                 4  
Protocol Violation                 0                 0                 0                 2  
Withdrawal by Subject                 0                 0                 0                 46  
Moved                 0                 0                 0                 16  
Site Terminated                 0                 0                 0                 4  
Unable/unwilling to return                 0                 0                 0                 25  



  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.
No text entered.

Reporting Groups
  Description
Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine

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 the Quadrivalent HPV vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the Quadrivalent HPV vaccine; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Group 2 - Base Study Monovalent HPV (Type 16) Vaccine

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 the Monovalent (HPV 16) HPV vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the Monovalent (HPV 16) HPV vaccine; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Group 3 - Base Study Placebo

The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 3 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 of the study.

Total Total of all reporting groups

Baseline Measures
    Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine     Group 2 - Base Study Monovalent HPV (Type 16) Vaccine     Group 3 - Base Study Placebo     Total  
Number of Participants  
[units: participants]
  2723     304     2732     5759  
Age  
[units: years]
Mean ± Standard Deviation
  20.2  ± 1.8     20.2  ± 1.74     20.3  ± 1.8     20.3  ± 1.8  
Age  
[units: Years]
Median ( Full Range )
  20  
  ( 16 to 24 )  
  20  
  ( 16 to 24 )  
  20  
  ( 16 to 24 )  
  20  
  ( 16 to 24 )  
Age, Customized [1]
[units: Participants]
       
16 to 24 Years of Age     2723     304     2732     5759  
Gender  
[units: participants]
       
Female     2723     304     2732     5759  
Male     0     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
       
Asian     151     27     165     343  
Black     136     5     167     308  
Hispanic American     567     93     566     1226  
Native American     10     2     10     22  
White     1600     171     1558     3329  
Other - Unspecified     259     6     266     531  
[1] Although the upper age limit for this study was 23 years old, four subjects aged 24 were randomized into the study.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Incidence of HPV 6/11/16/18-related Cervical Intraepithelial Neoplasia (CIN)(Any Grade), Adenocarcinoma In Situ (AIS) or Cervical Cancer   [ Time Frame: Follow-up through end of study (4 years) ]

2.  Primary:   Incidence of HPV 6/11/16/18-related External Genital Lesions (EGL) [Genital Warts, Vulvar/Vaginal Intraepithelial Neoplasia (Any Grade), Vulvar/Vaginal Cancer]   [ Time Frame: Follow-up through end of study (4 years) ]


  Serious Adverse Events
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Time Frame No text entered.
Additional Description Number of subjects at risk included randomized subjects who had follow-up. Differing numbers of subjects were at risk for serious vs. other adverse experiences (AEs) as both serious and non-serious AEs were collected in the base period and only serious AEs were collected in the extension period.

Reporting Groups
  Description
Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine

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 the Quadrivalent HPV vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the Quadrivalent HPV vaccine; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Group 2 - Base Study Monovalent HPV (Type 16) Vaccine

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 the Monovalent (HPV 16) HPV vaccine.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the Monovalent (HPV 16) HPV vaccine; from completion of the Vaccination Period at Month 7 through Month 48 of the study.

Group 3 - Base Study Placebo

The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 3 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 of the study.

Group 4 - Quadrivalent Human Papillomavirus Vaccine Extension

This group was comprises subjects from (1) Group 1

who received less than 3 doses of Quadrivalent HPV vaccine during the base study; (2) Group 2 subjects

who received Monovalent vaccine; and (3) Group 3 placebo subjects from the base study). Subjects

enrolled in the extension were vaccinated with the Quadrivalent HPV vaccine during the study extension.

No data on non-serious adverse events were collected on this group during the extension study, hence no data are entered for them in the table.


Serious Adverse Events
    Group 1 - Base Study Quadrivalent Human Papillomavirus Vaccine     Group 2 - Base Study Monovalent HPV (Type 16) Vaccine     Group 3 - Base Study Placebo     Group 4 - Quadrivalent Human Papillomavirus Vaccine Extension  
Total, serious adverse events          
# participants affected / at risk     50/2674 (1.87%)     4/299 (1.34%)     45/2673 (1.68%)     5/139 (3.60%)  
Blood and lymphatic system disorders          
Anaemia * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Gastrointestinal disorders          
Gastric Ulcer * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     0/2673 (0.00%)     1/139 (0.72%)  
Hepatobiliary disorders          
Cholecystitis * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Cholelithiasis * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Immune system disorders          
Allergy to vaccine * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     0/2673 (0.00%)     1/139 (0.72%)  
Infections and infestations          
Anogenital warts * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Appendicitis * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Breast abscess * 1        
# participants affected / at risk     0/2674 (0.00%)     1/299 (0.33%)     0/2673 (0.00%)     0/139 (0.00%)  
Endometritis decidual * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Enterocolitis infectious * 1        
# participants affected / at risk     0/2674 (0.00%)     1/299 (0.33%)     0/2673 (0.00%)     0/139 (0.00%)  
Gastroenteritis * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     1/139 (0.72%)  
Pelvic inflammatory disease * 1        
# participants affected / at risk     2/2674 (0.07%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Pharyngitis * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     0/2673 (0.00%)     1/139 (0.72%)  
Post procedural infection * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Pyelonephritis * 1        
# participants affected / at risk     2/2674 (0.07%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Tonsillitis streptococcal * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Urinary tract infection * 1        
# participants affected / at risk     2/2674 (0.07%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Varicella * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Injury, poisoning and procedural complications          
Abdominal injury † 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Accidental poisoning * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Head injury * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Injury * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Multiple injuries * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Operative haemorrhage * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Overdose * 1        
# participants affected / at risk     16/2674 (0.60%)     2/299 (0.67%)     21/2673 (0.79%)     0/139 (0.00%)  
Post procedural haemorrhage * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     3/2673 (0.11%)     0/139 (0.00%)  
Road traffic accident * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Metabolism and nutrition disorders          
Dehydration * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Musculoskeletal and connective tissue disorders          
Intervertebral disc protrusion * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Nervous system disorders          
Convulsion * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Dizziness * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Facial palsy * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Headache * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Syncope * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Transient ischemic attack * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     0/2673 (0.00%)     1/139 (0.72%)  
Pregnancy, puerperium and perinatal conditions          
Abortion threatened † 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Breech presentation * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Cephalo-pelvic disproportion * 1        
# participants affected / at risk     2/2674 (0.07%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Cervix dystocia * 1        
# participants affected / at risk     4/2674 (0.15%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Failed induction of labor * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Failed trial of labor * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Fetal distress syndrome * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Fetal malposition * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Oligohydramnios * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Pre-eclampsia * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     3/2673 (0.11%)     0/139 (0.00%)  
Premature labor * 1        
# participants affected / at risk     2/2674 (0.07%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Premature rupture of membranes * 1        
# participants affected / at risk     2/2674 (0.07%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Prolonged labor * 1        
# participants affected / at risk     2/2674 (0.07%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Transverse presentation * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Psychiatric disorders          
Completed suicide * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Renal and urinary disorders          
Renal failure * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Reproductive system and breast disorders          
Cervix haemorrhage uterine * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Respiratory, thoracic and mediastinal disorders          
Acute respiratory distress syndrome * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Asthma * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Bronchospasm * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Hyperventilation * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Pulmonary embolism * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Vascular disorders          
Deep vein thrombosis * 1        
# participants affected / at risk     0/2674 (0.00%)     0/299 (0.00%)     1/2673 (0.04%)     0/139 (0.00%)  
Hypotension * 1        
# participants affected / at risk     1/2674 (0.04%)     0/299 (0.00%)     0/2673 (0.00%)     0/139 (0.00%)  
Events were collected by systematic assessment
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 11.1




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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
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