Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Dose-Ranging Study of Quadrivalent Human Papillomavirus (HPV) (Types 6,11,16,18) L1 Virus-Like Particle (VLP) Vaccine (V501-007)(COMPLETED)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00365716
First received: August 16, 2006
Last updated: November 4, 2014
Last verified: November 2014
Results First Received: May 19, 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
Conditions: Papillomavirus Infections
Genital Diseases, Female
Interventions: Biological: Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20
Biological: Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40
Biological: Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80
Biological: Placebo (mcg) (Aluminum Adjuvant)225
Biological: Placebo (mcg) (Aluminum Adjuvant) 450

  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
Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20

The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 1 received a 20/40/40/20 formulation of quadrivalent human papillomavirus (qHPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.

Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40

The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 2 received a 40/40/40/40 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.

Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80

The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 3 received a 80/80/40/80 formulation of quadrivalent human papillomavirus (qHPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.

Placebo (mcg) (Aluminum Adjuvant) 225

The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 4 received placebo containing 225 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.

Placebo (mcg) (Aluminum Adjuvant) 450

The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 5 received placebo containing 450 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.

Extension 1 This group includes 241 international subjects, who either: (1) received placebo during the base study and continued in the Extension to receive a dose of GARDASIL (20/40/40/20 mcg formulation of qHPV vaccine) at Month 60 (plus 2 and 3 at Months 62 and 66, respectively, (2) received 3 doses of GARDASIL during the Base study and continued into the Extension to receive a fourth dose of GARDASIL at Month 60 for the purposes of investigating whether a fourth dose of vaccine (administered ~4.5 years following completion of a 3-dose primary regimen) induces HPV 6, 11, 16, and 18 antibody responses that characterize immune therapy.
Extension 2 This group includes 17 subjects from the United States, who received placebo during the base study and received 3 doses of qHPV vaccine during the Extension, or received less than 3 doses of the qHPV Vaccine during the base study and completed the dose regimen during the Extension.

Participant Flow for 4 periods

Period 1:   Base Study (Day 1 to Month 7)
    Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20     Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40     Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80     Placebo (mcg) (Aluminum Adjuvant) 225     Placebo (mcg) (Aluminum Adjuvant) 450     Extension 1     Extension 2  
STARTED     290     284     292     146     146     0     0  
COMPLETED     269     260     271     136     139     0     0  
NOT COMPLETED     21     24     21     10     7     0     0  
Randomized Not Vaccinated                 1                 2                 0                 0                 0                 0                 0  
Adverse Event                 0                 2                 0                 0                 1                 0                 0  
Lost to Follow-up                 4                 6                 6                 4                 0                 0                 0  
Unspecified                 0                 1                 0                 0                 0                 0                 0  
Pregnancy                 3                 2                 3                 1                 1                 0                 0  
Protocol Violation                 1                 2                 0                 1                 2                 0                 0  
Withdrawal by Subject                 12                 9                 12                 4                 3                 0                 0  

Period 2:   Long Term Follow-up (Month 7 toMonth 36)
    Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20     Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40     Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80     Placebo (mcg) (Aluminum Adjuvant) 225     Placebo (mcg) (Aluminum Adjuvant) 450     Extension 1     Extension 2  
STARTED     269     260     271     136     139     0     0  
COMPLETED     137     245     251     57     57     0     0  
NOT COMPLETED     132     15     20     79     82     0     0  
Proceeded to Extension 1                 114                 0                 0                 69                 75                 0                 0  
Lost to Follow-up                 6                 8                 5                 4                 3                 0                 0  
Moved                 3                 2                 1                 2                 0                 0                 0  
Unspecified                 2                 0                 0                 0                 1                 0                 0  
Protocol Violation                 0                 1                 1                 0                 0                 0                 0  
Withdrawal by Subject                 7                 4                 13                 4                 3                 0                 0  

Period 3:   Extension 1
    Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20     Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40     Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80     Placebo (mcg) (Aluminum Adjuvant) 225     Placebo (mcg) (Aluminum Adjuvant) 450     Extension 1     Extension 2  
STARTED     0     0     0     0     0     241     0  
COMPLETED     0     0     0     0     0     219     0  
NOT COMPLETED     0     0     0     0     0     22     0  
Lost to Follow-up                 0                 0                 0                 0                 0                 1                 0  
Unspecified                 0                 0                 0                 0                 0                 9                 0  
Moved                 0                 0                 0                 0                 0                 4                 0  
Withdrawal by Subject                 0                 0                 0                 0                 0                 3                 0  
Pregnancy                 0                 0                 0                 0                 0                 4                 0  
Protocol Violation                 0                 0                 0                 0                 0                 1                 0  

Period 4:   Extension 2
    Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20     Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40     Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80     Placebo (mcg) (Aluminum Adjuvant) 225     Placebo (mcg) (Aluminum Adjuvant) 450     Extension 1     Extension 2  
STARTED     0     0     0     0     0     0     17 [1]
COMPLETED     0     0     0     0     0     0     7  
NOT COMPLETED     0     0     0     0     0     0     10  
Lost to Follow-up                 0                 0                 0                 0                 0                 0                 2  
Unspecified                 0                 0                 0                 0                 0                 0                 3  
Withdrawal by Subject                 0                 0                 0                 0                 0                 0                 5  
[1] 17 Participants continued into Extension 2 from Extension 1



  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
Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20

The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 1 received a 20/40/40/20 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.

Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40

The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 2 received a 40/40/40/40 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.

Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80

The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 3 received a 80/80/40/80 formulation of quadrivalent human papillomavirus (qHPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.

Placebo (mcg) (Aluminum Adjuvant) 225

The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 4 received placebo containing 225 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.

Placebo (mcg) (Aluminum Adjuvant) 450

The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 5 received placebo containing 450 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.

The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.

Total Total of all reporting groups

Baseline Measures
    Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20     Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40     Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80     Placebo (mcg) (Aluminum Adjuvant) 225     Placebo (mcg) (Aluminum Adjuvant) 450     Total  
Number of Participants  
[units: participants]
  290     284     292     146     146     1158  
Age  
[units: years]
Mean ( Full Range )
  20.2  
  ( 16 to 23 )  
  20.0  
  ( 15 to 24 )  
  20.1  
  ( 16 to 23 )  
  20.0  
  ( 16 to 23 )  
  20.1  
  ( 13 to 23 )  
  20.0  
  ( 13 to 24 )  
Gender  
[units: participants]
           
Female     290     284     292     146     146     1158  
Male     0     0     0     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
           
Asian     7     11     5     6     5     34  
Black     25     32     27     12     7     103  
Hispanic American     15     15     10     10     11     61  
Indian     0     0     2     0     0     2  
Multi-racial     13     9     6     7     4     39  
Native American     2     4     2     0     1     9  
White     228     213     240     111     118     910  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Subjects With Injection Site Adverse Experiences   [ Time Frame: Days 1-5 following any vaccination visit ]

2.  Secondary:   Incidence of HPV 6-, 11-, 16- or 18-related Persistent Infection or Disease (Cervical Intraepithelial Neoplasia, Vulvar Intraepithelial Neoplasia, Vaginal Intraepithelial Neoplasia, Adenocarcinoma in Situ, Cervical Cancer, and Genital Warts)   [ Time Frame: Through 36 Months ]


  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
No text entered.


  More Information
  Hide More Information

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.


Results Point of Contact:  
Name/Title: Senior Vice President,Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com


Publications:


Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00365716     History of Changes
Other Study ID Numbers: V501-007, 2006_516
Study First Received: August 16, 2006
Results First Received: May 19, 2010
Last Updated: November 4, 2014
Health Authority: United States: Food and Drug Administration