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Vaccine To Prevent Cervical Intraepithelial Neoplasia or Cervical Cancer in Younger Healthy Participants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00128661
First received: August 8, 2005
Last updated: May 24, 2012
Last verified: May 2012
Results First Received: December 15, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions: Cervical Cancer
Precancerous Condition
Interventions: Biological: human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine
Biological: hepatitis A inactivated virus vaccine

  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
Solicited symptoms were collected for 3730 and 3740 subjects instead of the 3727 and 3739 subjects who were randomized in the study in the Cervarix and the Havrix groups, respectively. These 4 sujects received both vaccines and were included in the denominator of both arm based on the actual vaccine type administered.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Participant Flow:   Overall Study
    Cervarix Group   Havrix Group
STARTED   3727   3739 
COMPLETED   3453   3481 
NOT COMPLETED   274   258 
Adverse Event                14                11 
Lost to Follow-up                10                7 
Withdrawal by Subject                243                232 
Unspecified                7                8 



  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
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Total Total of all reporting groups

Baseline Measures
   Cervarix Group   Havrix Group   Total 
Overall Participants Analyzed 
[Units: Participants]
 3727   3739   7466 
Age 
[Units: Years]
Mean (Standard Deviation)
     
Years   21.1  (2.3)   21.1  (2.3)   21.1  (2.3) 
Gender 
[Units: Subjects]
     
Female   3727   3739   7466 
Male   0   0   0 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.   [ Time Frame: From Month 6 up to Month 48 ]

2.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: From Month 6 up to Month 48 ]

3.  Secondary:   Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type   [ Time Frame: From Month 6 up to Month 48 ]

4.  Secondary:   Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases   [ Time Frame: From Month 6 up to Month 48 ]

5.  Secondary:   Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.   [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]

6.  Secondary:   Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort   [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]

7.  Secondary:   HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)   [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]

8.  Secondary:   HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)   [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]
  Hide Outcome Measure 8

Measure Type Secondary
Measure Title HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)
Measure Description

Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Inhibition Enzyme Immunoassay (EIA) and expressed as geometric mean antibody titers (GMTs).

Seronegative (Sero-) subjects=antibody concentration below 110 EL.U/mL prior to vaccination.

Seropositive (Sero+) subjects=antibody concentration equal to or above 110 EL.U/mL prior to vaccination.

Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).

Time Frame Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48  
Safety Issue No  

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.
The ATP cohort for immunogenicity included subjects who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and during the 48-month follow-up period, who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6) and for whom immunogenicity results were available.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
   Cervarix Group   Havrix Group 
Participants Analyzed 
[Units: Participants]
 203   176 
HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) 
[Units: Titers]
Geometric Mean (95% Confidence Interval)
   
HPV-18 [before vaccination] (N=203;176)   55.0 
 (55.0 to 55.0) 
 55.7 
 (54.7 to 56.7) 
HPV-18 [at Month 1] (N=197;173)   99.1 
 (88.0 to 111.5) 
 55.3 
 (54.7 to 55.8) 
HPV-18 [at Month 6] (N=195;175)   111.4 
 (100.2 to 123.9) 
 55.4 
 (54.6 to 56.3) 
HPV-18 [at Month 7] (N=198;176)   823.6 
 (737.7 to 919.5) 
 55.0 
 (55.0 to 55.0) 
HPV-18 [at Month 12] (N=182;166)   231.1 
 (203.2 to 262.7) 
 56.7 
 (54.7 to 58.8) 
HPV-18 [at Month 18] (N=28;20)   121.8 
 (89.5 to 165.8) 
 55.0 
 (55.0 to 55.0) 
HPV-18 [at Month 24] (N=170;154)   140.8 
 (123.8 to 160.2) 
 55.0 
 (55.0 to 55.0) 
HPV-18 [at Month 30] (N=17;19)   89.5 
 (67.6 to 118.7) 
 55.0 
 (55.0 to 55.0) 
HPV-18 [at Month 36] (N=167;145)   107.9 
 (96.0 to 121.2) 
 55.0 
 (55.0 to 55.0) 
HPV-18 [at Month 42] (N=25;19)   103.3 
 (80.3 to 132.9) 
 55.0 
 (55.0 to 55.0) 
HPV-18 [at Month 48 (N=179;150)   96.9 
 (87.7 to 107.0) 
 56.7 
 (54.0 to 59.6) 

No statistical analysis provided for HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)



9.  Secondary:   Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.   [ Time Frame: Within 60 minutes after vaccination ]

10.  Secondary:   Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.   [ Time Frame: Within 60 minutes after vaccination ]

11.  Secondary:   Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.   [ Time Frame: From Day 3 to Day 6 after vaccination ]

12.  Secondary:   Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.   [ Time Frame: From Day 3 to Day 6 after vaccination ]

13.  Secondary:   Number of Subjects Reporting Serious Adverse Events (SAEs).   [ Time Frame: During the entire study period (From Month 0 up to Month 48). ]

14.  Secondary:   Number of Subjects Reporting Unsolicited Adverse Events (AEs).   [ Time Frame: During the entire study period (From Month 0 up to Month 48). ]

15.  Secondary:   Number of Subjects With All Possible Pregnancy Outcomes   [ Time Frame: During the entire study period (From Month 0 up to Month 48). ]

16.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: During the first year of follow-up period ]

17.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: During the second year of follow-up period ]

18.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: During the third year of follow-up period ]

19.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: From the fourth year follow-up period ]

20.  Secondary:   Number of Subjects Reporting Unsolicited Adverse Events (AEs).   [ Time Frame: within 30 days (Days 0-29) after vaccination ]


  Serious Adverse Events


  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
The following analysis "occurence of histopathologically confirmed CIN2+ cases associated with HPV16 or HPV18 infection was not performed, in accordance with the Statistical Analysis Plan submitted to the FDA.


  More Information
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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.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Kreimer AR, Struyf F, Del Rosario-Raymundo MR, Hildesheim A, Skinner SR, Wacholder S, Garland SM, Herrero R, David MP, Wheeler CM; Costa Rica Vaccine Trial Study Group Authors., González P, Jiménez S, Lowy DR, Pinto LA, Porras C, Rodriguez AC, Safaeian M, Schiffman M, Schiller JT, Schussler J, Sherman ME; PATRICIA Study Group Authors., Bosch FX, Castellsague X, Chatterjee A, Chow SN, Descamps D, Diaz-Mitoma F, Dubin G, Germar MJ, Harper DM, Lewis DJ, Limson G, Naud P, Peters K, Poppe WA, Ramjattan B, Romanowski B, Salmeron J, Schwarz TF, Teixeira JC, Tjalma WA; HPV PATRICIA Principal Investigators/Co-Principal Investigator Collaborators.; GSK Vaccines Clinical Study Support Group.. Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials. Lancet Oncol. 2015 Jul;16(7):775-86. doi: 10.1016/S1470-2045(15)00047-9.


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00128661     History of Changes
Obsolete Identifiers: NCT00344357
Other Study ID Numbers: CDR0000441189
NCI-04-C-N191
NCI-590299/009
GSK-590299/009 ( Other Identifier: GSK Bio )
Study First Received: August 8, 2005
Results First Received: December 15, 2011
Last Updated: May 24, 2012
Health Authority: United States: Food and Drug Administration