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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
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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 ]

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 ]

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). ]
  Hide Outcome Measure 15

Measure Type Secondary
Measure Title Number of Subjects With All Possible Pregnancy Outcomes
Measure Description The range of possible pregnancy outcomes was: Pregnancy loss, Pregnancy resolved alive, and Unresolved pregnancy.
Time Frame During the entire study period (From Month 0 up to Month 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 analysis was performed on the Total Vaccinated Cohort, on all pregnant subjects.

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]
 2123   2129 
Number of Subjects With All Possible Pregnancy Outcomes 
[Units: Subjects]
   
Pregnancy loss   317   294 
Pregnancy resolved alive   1756   1766 
Unresolved pregnancy   50   69 

No statistical analysis provided for Number of Subjects With All Possible Pregnancy Outcomes



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
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Time Frame Solicited AEs: within 60 minutes after vaccination for all subjects; From Day 3 to Day 6 post-vaccination in the subset. SAEs: From Month 0 up to Month 48. Unsolicited AEs: From Month 0 up to Month 48 and Within 30 days (Days 0-29) after vaccination
Additional Description Solicited AEs were collected and tabulated for all subjects and for a 10% random subset of participants.

Frequency Threshold
Threshold above which other adverse events are reported   5  

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.

Other Adverse Events
    Cervarix Group   Havrix Group
Total, other (not including serious) adverse events     
# participants affected / at risk   1627/3730 (43.62%)   1610/3740 (43.05%) 
Gastrointestinal disorders     
Gastrointestinal inflammation * [3]     
# participants affected / at risk   263/3727 (7.06%)   249/3739 (6.66%) 
General disorders     
Pain † [4]     
# participants affected / at risk   1627/3730 (43.62%)   1610/3740 (43.05%) 
Redness † [4]     
# participants affected / at risk   544/3730 (14.58%)   501/3740 (13.40%) 
Swelling † [4]     
# participants affected / at risk   207/3730 (5.55%)   201/3740 (5.37%) 
Fatigue † [4]     
# participants affected / at risk   512/3730 (13.73%)   502/3740 (13.42%) 
Myalgia † [4]     
# participants affected / at risk   257/3730 (6.89%)   232/3740 (6.20%) 
Gastrointestinal † [4]     
# participants affected / at risk   191/3730 (5.12%)   171/3740 (4.57%) 
Headache † [4]     
# participants affected / at risk   714/3730 (19.14%)   718/3740 (19.20%) 
Fever † [4]     
# participants affected / at risk   472/3730 (12.65%)   477/3740 (12.75%) 
Pain † [5]     
# participants affected / at risk   202/380 (53.16%)   74/376 (19.68%) 
Swelling † [5]     
# participants affected / at risk   23/380 (6.05%)   1/376 (0.27%) 
Fatigue † [5]     
# participants affected / at risk   214/380 (56.32%)   189/376 (50.27%) 
Myalgia † [5]     
# participants affected / at risk   250/380 (65.79%)   211/376 (56.12%) 
Arthralgia † [5]     
# participants affected / at risk   44/380 (11.58%)   32/376 (8.51%) 
Gastrointestinal † [5]     
# participants affected / at risk   157/380 (41.32%)   119/376 (31.65%) 
Headache † [5]     
# participants affected / at risk   247/380 (65.00%)   242/376 (64.36%) 
Rash † [5]     
# participants affected / at risk   31/380 (8.16%)   26/376 (6.91%) 
Fever † [5]     
# participants affected / at risk   43/380 (11.32%)   37/376 (9.84%) 
Infections and infestations     
Influenza * [6]     
# participants affected / at risk   263/3727 (7.06%)   293/3739 (7.84%) 
Influenza * [3]     
# participants affected / at risk   903/3727 (24.23%)   950/3739 (25.41%) 
Vaginal infection * [3]     
# participants affected / at risk   709/3727 (19.02%)   763/3739 (20.41%) 
Vulvovaginal candidiasis * [3]     
# participants affected / at risk   714/3727 (19.16%)   678/3739 (18.13%) 
Urinary tract infection * [3]     
# participants affected / at risk   555/3727 (14.89%)   565/3739 (15.11%) 
Upper respiratory tract infection * [3]     
# participants affected / at risk   324/3727 (8.69%)   327/3739 (8.75%) 
Dengue fever * [3]     
# participants affected / at risk   174/3727 (4.67%)   190/3739 (5.08%) 
Musculoskeletal and connective tissue disorders     
Myalgia * [6]     
# participants affected / at risk   355/3727 (9.53%)   166/3739 (4.44%) 
Myalgia * [3]     
# participants affected / at risk   386/3727 (10.36%)   189/3739 (5.05%) 
Nervous system disorders     
Headache * [6]     
# participants affected / at risk   218/3727 (5.85%)   214/3739 (5.72%) 
Headache * [3]     
# participants affected / at risk   324/3727 (8.69%)   315/3739 (8.42%) 
Reproductive system and breast disorders     
Menstruation irregular * [3]     
# participants affected / at risk   1021/3727 (27.39%)   1011/3739 (27.04%) 
Events were collected by systematic assessment
* Events were collected by non-systematic assessment
[3] From Month 0 up to Month 48
[4] Within 60 minutes after vaccination.
[5] From Day 3 to Day 6 post-vaccination, in a 10% random subset of participants.
[6] Within 30 days (Days 0-29) after vaccination



  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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