Cervical Intraepithelial Neoplasm (CIN) in Women (Gardasil)(V501-015 AM5; EXT1; EXT2(AM1))

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00092534
First received: September 23, 2004
Last updated: October 17, 2012
Last verified: October 2012
Results First Received: July 20, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Conditions: Cervical Cancer
Genital Warts
Interventions: Biological: Gardasil, human papillomavirus (type 6, 11, 16, 18) recombinant vaccine
Biological: Matching 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
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
Quadrivalent Human Papillomavirus Vaccine (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 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.

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 of the study.

Extension Study This group includes 581 subjects who received placebo during the base study, (Group 2-Base Study) and 13 additional subjects who were randomized to the active vaccine arm of the base study (from Group 1-Base Study), but received fewer than the full three doses of Quadrivalent HPV vaccine during the base study. 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:   Base Study Vaccination Period
    Quadrivalent Human Papillomavirus Vaccine (Group 1)     Placebo (Group 2)     Extension Study  
STARTED     6087     6080     0  
COMPLETED     5916     5954     0  
NOT COMPLETED     171     126     0  
Randomized not Vaccinated                 5                 5                 0  
Adverse Event                 3                 1                 0  
Death                 5                 4                 0  
Lost to Follow-up                 41                 37                 0  
Physician Decision                 1                 0                 0  
Pregnancy                 9                 7                 0  
Protocol Violation                 2                 1                 0  
Withdrawal by Subject                 85                 58                 0  
Moved                 14                 12                 0  
New Medical History (Not AEs)                 5                 0                 0  
Travel                 1                 0                 0  
Site Closed                 0                 1                 0  

Period 2:   Base Study Follow Up Period
    Quadrivalent Human Papillomavirus Vaccine (Group 1)     Placebo (Group 2)     Extension Study  
STARTED     5942 [1]   5971 [1]   0  
COMPLETED     5626     5277     0  
NOT COMPLETED     316     694     0  
Adverse Event                 2                 4                 0  
Death                 2                 1                 0  
Lost to Follow-up                 120                 146                 0  
Pregnancy                 6                 10                 0  
Protocol Violation                 1                 2                 0  
Withdrawal by Subject                 71                 62                 0  
Moved                 62                 58                 0  
Travel                 10                 7                 0  
Site Closed                 0                 2                 0  
Subjects continuing                 27                 31                 0  
Subjects in extension                 15                 371                 0  
[1] Includes subjects who did not receive 3 doses of vaccine/placebo but continued into the follow-up.

Period 3:   Extension Study
    Quadrivalent Human Papillomavirus Vaccine (Group 1)     Placebo (Group 2)     Extension Study  
STARTED     0     0     594  
COMPLETED     0     0     449  
NOT COMPLETED     0     0     145  
Lost to Follow-up                 0                 0                 41  
Physician Decision                 0                 0                 1  
Pregnancy                 0                 0                 12  
Withdrawal by Subject                 0                 0                 18  
Moved                 0                 0                 6  
Travel                 0                 0                 2  
Site Closed                 0                 0                 21  
Study Ended                 0                 0                 29  
Protocol Deviation                 0                 0                 15  



  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
Quadrivalent Human Papillomavirus Vaccine (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 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.

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 of the study.

Total Total of all reporting groups

Baseline Measures
    Quadrivalent Human Papillomavirus Vaccine (Group 1)     Placebo (Group 2)     Total  
Number of Participants  
[units: participants]
  6087     6080     12167  
Age, Customized [1]
[units: participants]
     
Between 15 and 26 years     6087     6080     12167  
Age  
[units: years]
Mean ± Standard Deviation
  20.0  ± 2.2     19.9  ± 2.1     19.9  ± 2.1  
Gender  
[units: participants]
     
Female     6087     6080     12167  
Male     0     0     0  
Race/Ethnicity [2]
[units: participants]
     
Asian     151     135     286  
Black     171     227     398  
Hispanic American     555     557     1112  
Native American     1     1     2  
White     4584     4550     9134  
Other-Unspecified     625     610     1235  
[1] Age for study subjects was recorded at the time of subject entry into the base study.
[2] Subject race was determined at subject entry into the base study.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Tolerability; Incidence of the Composite Endpoint of HPV 16 or HPV 18 Related CIN2/3 or Invasive Cervical Carcinoma After Completion of the Vaccination Series for Relevant HPV Type   [ Time Frame: Follow-up through end of study (4 years) ]

2.  Secondary:   Subjects With Anti-HPV 6 Titer >/= 20 mMU/mL   [ Time Frame: week 4 Postdose 3 (4 weeks after 3rd vaccine dose) ]

3.  Secondary:   Subjects With Anti-HPV 11 Titer >/= 16 mMU/mL   [ Time Frame: week 4 Postdose 3 ]

4.  Secondary:   Subjects With Anti-HPV 16 Titer >/= 20 mMU/mL   [ Time Frame: week 4 Postdose 3 ]

5.  Secondary:   Subjects With Anti-HPV 18 Titer >/= 24 mMU/mL   [ Time Frame: week 4 Postdose 3 ]


  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
Quadrivalent Human Papillomavirus Vaccine (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 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.

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 of the study.

Extension Study

This group includes 581 subjects who received placebo during the base study, (Group 2-Base Study) and 13 additional subjects who were randomized to the active vaccine arm of the base study (from Group 1-Base Study), but received fewer than the full three doses of Quadrivalent HPV vaccine during the base study. 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.

Extension study includes subjects from Group 2-Base Study who were vaccinated with quadrivalent HPV vaccine.

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
    Quadrivalent Human Papillomavirus Vaccine (Group 1)     Placebo (Group 2)     Extension Study  
Total, serious adverse events        
# participants affected     46     56     1  
Blood and lymphatic system disorders        
Disseminated intravascular coagulation * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Cardiac disorders        
Aortic valve disease * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Cardiac arrest * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Myocarditis * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Pericarditis * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Gastrointestinal disorders        
Abdominal pain * 1      
# participants affected / at risk     1/6021 (0.02%)     1/6033 (0.02%)     0/594 (0.00%)  
Gastritis * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Reflux oesophagitis * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
General disorders        
Chills * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Face oedema * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Pyrexia * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Injection site joint movement impairment * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Injection site pain * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Hepatobiliary disorders        
Cholelithiasis * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Immune system disorders        
Anaphylactic reaction * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Hypersensitivty * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Infections and infestations        
Appendicitis * 1      
# participants affected / at risk     2/6021 (0.03%)     0/6033 (0.00%)     0/594 (0.00%)  
Cervicitis * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Endometritis * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Gastroenteritis * 1      
# participants affected / at risk     2/6021 (0.03%)     1/6033 (0.02%)     0/594 (0.00%)  
Gastrointestinal infection * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Infective thrombosis * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Pelvic Inflammatory disease * 1      
# participants affected / at risk     0/6021 (0.00%)     2/6033 (0.03%)     0/594 (0.00%)  
Pneumonia * 1      
# participants affected / at risk     2/6021 (0.03%)     1/6033 (0.02%)     0/594 (0.00%)  
Pyelonephritis * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Sepsis * 1      
# participants affected / at risk     2/6021 (0.03%)     0/6033 (0.00%)     0/594 (0.00%)  
Septic Shock * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Typhoid fever * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Urinary tract infection * 1      
# participants affected / at risk     0/6021 (0.00%)     2/6033 (0.03%)     0/594 (0.00%)  
Uterine infection * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Injury, poisoning and procedural complications        
Chemical poisoning * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Failed forceps delivery * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Intentional overdose * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Multiple injuries * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Overdose * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Post procedural haemorrhage * 1      
# participants affected / at risk     1/6021 (0.02%)     1/6033 (0.02%)     0/594 (0.00%)  
Road traffic accident * 1      
# participants affected / at risk     3/6021 (0.05%)     2/6033 (0.03%)     0/594 (0.00%)  
Thermal burn * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Musculoskeletal and connective tissue disorders        
Pain in extremity * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)        
Thyroid cancer * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Nervous system disorders        
Convulsion * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Dizziness * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Headache * 1      
# participants affected / at risk     2/6021 (0.03%)     1/6033 (0.02%)     0/594 (0.00%)  
Pregnancy, puerperium and perinatal conditions        
Abortion threatened * 1      
# participants affected / at risk     3/6021 (0.05%)     4/6033 (0.07%)     0/594 (0.00%)  
Breech presentation * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Brow presentation * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Cephalo-pelvic disproportion * 1      
# participants affected / at risk     0/6021 (0.00%)     5/6033 (0.08%)     0/594 (0.00%)  
Cervix dystocia * 1      
# participants affected / at risk     1/6021 (0.02%)     1/6033 (0.02%)     0/594 (0.00%)  
Ectopic pregnancy † 1      
# participants affected / at risk     1/6021 (0.02%)     1/6033 (0.02%)     0/594 (0.00%)  
Failed trial of labour * 1      
# participants affected / at risk     3/6021 (0.05%)     3/6033 (0.05%)     0/594 (0.00%)  
Foetal distress syndrome * 1      
# participants affected / at risk     3/6021 (0.05%)     2/6033 (0.03%)     0/594 (0.00%)  
Foetal malpresentation * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Hyperemesis gravidarum * 1      
# participants affected / at risk     2/6021 (0.03%)     0/6033 (0.00%)     0/594 (0.00%)  
Imminent abortion * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     1/594 (0.17%)  
Oligohydramnios * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Postpartum haemorrhage * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Pre-eclampsia * 1      
# participants affected / at risk     1/6021 (0.02%)     1/6033 (0.02%)     0/594 (0.00%)  
Pregnancy induced hypertension * 1      
# participants affected / at risk     2/6021 (0.03%)     1/6033 (0.02%)     0/594 (0.00%)  
Premature labour * 1      
# participants affected / at risk     3/6021 (0.05%)     5/6033 (0.08%)     0/594 (0.00%)  
Premature rupture of membranes * 1      
# participants affected / at risk     1/6021 (0.02%)     1/6033 (0.02%)     0/594 (0.00%)  
Prolonged pregnancy * 1      
# participants affected / at risk     0/6021 (0.00%)     2/6033 (0.03%)     0/594 (0.00%)  
Uterine contractions during pregnancy * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Cervical incompetence * 1      
# participants affected / at risk     0/6021 (0.00%)     2/6033 (0.03%)     0/594 (0.00%)  
Psychiatric disorders        
Bipolar disorder * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Completed suicide * 1      
# participants affected / at risk     0/6021 (0.00%)     2/6033 (0.03%)     0/594 (0.00%)  
Panic attack * 1      
# participants affected / at risk     0/6021 (0.00%)     0/6033 (0.00%)     1/594 (0.17%)  
Renal and urinary disorders        
Urinary retention * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Reproductive system and breast disorders        
Cervix haemorrhage uterine * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Ovarian cyst * 1      
# participants affected / at risk     2/6021 (0.03%)     0/6033 (0.00%)     0/594 (0.00%)  
Vaginal laceration * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Vulvovaginal discomfort * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Respiratory, thoracic and mediastinal disorders        
Asphyxia * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Asthma * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Neonatal asphyxia * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Pneumomediastinum * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Pulmonary embolism * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Skin and subcutaneous tissue disorders        
Cutaneous vasculitis * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Dermatitis contact * 1      
# participants affected / at risk     0/6021 (0.00%)     1/6033 (0.02%)     0/594 (0.00%)  
Vascular disorders        
Deep vein thrombosis * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Hypertension * 1      
# participants affected / at risk     1/6021 (0.02%)     1/6033 (0.02%)     0/594 (0.00%)  
Thrombophlebitis * 1      
# participants affected / at risk     1/6021 (0.02%)     0/6033 (0.00%)     0/594 (0.00%)  
Events were collected by systematic assessment
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 11.0




  Other Adverse Events


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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


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
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Results Point of Contact:  
Name/Title: Executive Vice President, Clinical and Quantitative Sciences
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372


Publications:

Publications automatically indexed to this study:


Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00092534     History of Changes
Other Study ID Numbers: 2004_082, V501-015
Study First Received: September 23, 2004
Results First Received: July 20, 2009
Last Updated: October 17, 2012
Health Authority: United States: Food and Drug Administration