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

History of Changes

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
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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.
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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 ]

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2. Secondary:

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

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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 ]

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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 ]

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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 ]

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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 ]

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9. Secondary:

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

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10. Secondary:

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

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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
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]	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 ]

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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 ]

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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). ]

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14. Secondary:

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

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15. Secondary:

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

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16. Secondary:

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

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17. Secondary:

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

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18. Secondary:

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

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19. Secondary:

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

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20. Secondary:

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

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Serious Adverse Events

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Other Adverse Events

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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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