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

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ClinicalTrials.gov Identifier: NCT00128661
Recruitment Status : Completed
First Posted : August 10, 2005
Results First Posted : May 2, 2012
Last Update Posted : June 1, 2012
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, 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

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 
Other                7                8 



  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
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

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 ]
  Show Outcome Measure 1

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

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 ]
  Show Outcome Measure 3

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 ]
  Show Outcome Measure 4

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 ]
  Show Outcome Measure 5

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 ]
  Show Outcome Measure 6

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 ]
  Show Outcome Measure 7

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 ]
  Show Outcome Measure 8

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

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

Measure Type Secondary
Measure Title Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.
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 Within 60 minutes after vaccination  

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 
Participants Analyzed 
[Units: Participants]
 		 3730   3740 
Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. 
[Units: Subjects]
 		   
Any fatigue   512   502 
Grade 3 fatigue   6   5 
Any myalgia   257   232 
Grade 3 myalgia   0   1 
Any arthralgia   58   64 
Grade 3 arthralgia   0   1 
Any gastrointestinal   191   171 
Grade 3 gastrointestinal   0   0 
Any headache   714   718 
Grade 3 headache   2   0 
Any rash   15   17 
Grade 3 rash   0   0 
Any urticaria   19   21 
Grade 3 urticaria   0   0 
Fever (oral) >= 37.5°C   472   477 
Fever (oral) > 39.0°C   0   0 

No statistical analysis provided for Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.



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 ]
  Show Outcome Measure 11

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  

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 
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). ]
  Show Outcome Measure 13

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

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

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

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

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

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

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


  Serious Adverse Events


  Other Adverse Events


  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
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