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  
Number of Participants  
[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
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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 ]
  Hide Outcome Measure 5

Measure Type Secondary
Measure Title Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.
Measure Description

Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Enzyme linked immunosorbent assay (ELISA) and expressed as geometric mean titers (GMTs).

Seronegative subjects = antibody concentration below 8 ELISA Units per millilitre (EL.U/mL) prior to vaccination.

Seropositive subjects=antibody concentration equal to or above 8 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  
Number of Participants Analyzed  
[units: participants]
  196     157  
Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.  
[units: Titers]
Geometric Mean ( 95% Confidence Interval )
   
HPV-16 [before vaccination] (N=194;156)     6.7  
  ( 5.7 to 7.8 )  
  8.2  
  ( 6.7 to 10.0 )  
HPV-16 [at Month 1] (N=196,157)     646.6  
  ( 549.3 to 761.1 )  
  7.9  
  ( 6.5 to 9.6 )  
HPV-16 [at Month 6] (N=195,156)     771.5  
  ( 668.3 to 890.7 )  
  8.4  
  ( 6.9 to 10.3 )  
HPV-16 [at Month 7] (N=195,157)     3261  
  ( 2959 to 3595 )  
  8.5  
  ( 6.9 to 10.3 )  
HPV-16 [at Month 12] (N=182,146)     2090  
  ( 1822 to 2398 )  
  8.3  
  ( 6.7 to 10.4 )  
HPV-16 [at Month 18] (N=25,17)     1045  
  ( 776.0 to 1408 )  
  10.4  
  ( 4.8 to 22.7 )  
HPV-16 [at Month 24] (N=175,137)     1486  
  ( 1293 to 1709 )  
  8.6  
  ( 6.9 to 10.7 )  
HPV-16 [at Month 30] (N=19,15)     1070  
  ( 747.5 to 1532 )  
  11.9  
  ( 5.1 to 28.0 )  
HPV-16 [at Month 36] (N=163,132)     1256  
  ( 1080 to 1461 )  
  9.0  
  ( 7.4 to 11.0 )  
HPV-16 [at Month 42] (N=22,18)     1259  
  ( 879.4 to 1802 )  
  6.1  
  ( 4.0 to 9.4 )  
HPV-16 [at Month 48] (N=172,131)     1155  
  ( 1009 to 1322 )  
  9.5  
  ( 7.7 to 11.7 )  

No statistical analysis provided for Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.



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 ]

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 ]
  Hide Outcome Measure 12

Measure Type Secondary
Measure Title Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.
Measure Description Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and fever (Fever = oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy.Grade 3 urticaria = urticaria distributed on at least 4 body areas. Grade 3 fever = oral temperature > 39.0°C.
Time Frame From Day 3 to Day 6 after vaccination  
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 Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

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  
Number of Participants Analyzed  
[units: participants]
  380     376  
Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.  
[units: Subjects]
   
Any pain     214     189  
Grade 3 pain     2     0  
Any myalgia     250     211  
Grade 3 myalgia     1     0  
Any arthralgia     44     32  
Grade 3 arthralgia     0     0  
Any gastrointestinal     157     119  
Grade 3 gastrointestinal     0     1  
Any headache     247     242  
Grade 3 headache     1     2  
Any rash     31     26  
Grade 3 rash     0     0  
Any urticaria     3     1  
Grade 3 urticaria     0     0  
Fever (oral) >= 37.5°C     43     37  
Fever (oral) > 39.0°C     0     0  

No statistical analysis provided for Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.



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.


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