Vaccine To Prevent Cervical Intraepithelial Neoplasia or Cervical Cancer in Younger Healthy Participants
Study Details
Study Description
Brief Summary
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer form forming, growing, or coming back. Vaccines may help the body build an effective immune response against human papillomavirus and may be effective in preventing cervical intraepithelial neoplasia or cervical cancer. It is not yet known whether human papillomavirus vaccine is more effective than hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer.
PURPOSE: This randomized phase III trial is studying human papillomavirus vaccine to see how well it works compared to hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer in younger healthy participants.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
OBJECTIVES:
Primary
•Demonstrate the efficacy of the candidate vaccine, human papillomavirus 16/18 (HPV 16/18) L1 virus-like particle (VLP)/AS04 vaccine compared with control in preventing grade 2 or 3 cervical intraepithelial neoplasia, adenocarcinoma in situ of the cervix, or invasive cervical cancer (CIN2+) associated with HPV 16 or HPV 18 cervical infection in younger healthy participants who are negative for HPV DNA by polymerase chain reaction (PCR) for the corresponding HPV type at months 0 and 6.
Secondary
-
Determine the duration of protection against HPV 16 or HPV 18 cervical infection in participants treated with the HPV 16/18 L1 VLP/AS04 vaccine.
-
Determine the safety of this vaccine in these participants, regardless of their initial HPV 16/18 DNA status.
-
Evaluate the efficacy of the candidate vaccine, HPV 16/18 L1 VLP/AS04 vaccine compared with control in preventing CIN2+ associated with any oncogenic HPV type cervical infection in participants who are negative for HPV DNA by PCR for the corresponding HPV type at months 0 and 6.
-
Compare the efficacy of the candidate vaccine with control in preventing CIN2+ associated with HPV 16 or HPV 18 cervical infection, detected within the lesional component of the cervical tissue specimen by PCR, in participants who are negative for HPV DNA by PCR for the corresponding HPV type at months 0 and 6 and by enzyme-linked immunosorbent assay (ELISA) at month 0.
-
Compare the efficacy of the candidate vaccine with control in preventing persistent HPV 16 or HPV 18 cervical infection in these participants.
-
Determine the immunogenicity of HPV 16/18 L1 VLP/AS04 vaccine by ELISA and V5/J4 monoclonal antibody inhibition enzyme immunoassay in the first 600 participants randomized to receive HPV 16/18 L1 VLP/AS04 vaccine.
OUTLINE: This is a randomized, controlled, double-blind, parallel-group study. Participants are randomized to 1 of 2 treatment arms.
-
Arm I: Participants receive human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine intramuscularly (IM) once in months 0, 1, and 6.
-
Arm II: Participants receive hepatitis A vaccine (Havrix®) IM once in months 0, 1, and
After completion of study treatment, participants are followed at 6 months and then at least annually for 3 years.
PROJECTED ACCRUAL: Approximately 7,500 participants will be accrued for this study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Biological: human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine
Three doses of Cervarix vaccine administered on a 0, 1, 6-month schedule
|
| Active Comparator: 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. |
Biological: hepatitis A inactivated virus vaccine
Three doses of Havrix vaccine administered on a 0, 1, 6-month schedule
|
Outcome Measures
Primary Outcome Measures
- Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen. [From Month 6 up to Month 48]
CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer. Preceding cervical cytology means the last cervical cytology specimen collected before the histopathology specimen was obtained. Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) by polymerase chain reaction (PCR) at Month 0 and Month 6 for the corresponding HPV-type.
Secondary Outcome Measures
- Number of Cervical Infection With HPV16 or HPV18. [From Month 6 up to Month 48]
Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
- Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type [From Month 6 up to Month 48]
Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 detected by polymerase chain reaction (PRC) in the preceding cervical cytology specimen. Note: The assay did not distinguish between HPV types 68 and 73. CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
- Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases [From Month 6 up to Month 48]
Persistent incident HPV-16 and /or HPV-18 cervical infection had to fulfil the following criteria: first detection after the 6-month visit, 2 same type HPV positive (by PCR) test results 10+ months apart, and no intervening HPV negative tests for the corresponding type. Persistent HPV16 or HPV18 cervical infection = detection of the same HPV type by polymerase chain reaction (PCR) in cervical samples from all consecutive evaluations over approximately 12 months. Subjects were HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type.
- Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. [Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48]
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)
- Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort [Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48]
Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohortby Enzyme linked immunosorbent assay (ELISA) and expressed as geometric mean titers (GMTs). Seronegative (Sero-) subjects=antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects=antibody concentration equal to or above 7 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).
- HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) [Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48]
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 41 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects=antibody concentration equal to or above 41 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).
- HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) [Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48]
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).
- Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. [Within 60 minutes after vaccination]
Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).
- Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. [Within 60 minutes after vaccination]
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.
- Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. [From Day 3 to Day 6 after vaccination]
Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).
- Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. [From Day 3 to Day 6 after vaccination]
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.
- Number of Subjects Reporting Serious Adverse Events (SAEs). [During the entire study period (From Month 0 up to Month 48).]
SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.
- Number of Subjects Reporting Unsolicited Adverse Events (AEs). [During the entire study period (From Month 0 up to Month 48).]
An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
- Number of Subjects With All Possible Pregnancy Outcomes [During the entire study period (From Month 0 up to Month 48).]
The range of possible pregnancy outcomes was: Pregnancy loss, Pregnancy resolved alive, and Unresolved pregnancy.
- Number of Cervical Infection With HPV16 or HPV18. [During the first year of follow-up period]
Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
- Number of Cervical Infection With HPV16 or HPV18. [During the second year of follow-up period]
Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
- Number of Cervical Infection With HPV16 or HPV18. [During the third year of follow-up period]
Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
- Number of Cervical Infection With HPV16 or HPV18. [From the fourth year follow-up period]
Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
- Number of Subjects Reporting Unsolicited Adverse Events (AEs). [within 30 days (Days 0-29) after vaccination]
An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
•Healthy participants
- Deemed to be in good general health by history and physical examination
•Resident of Guanacaste Province of Costa Rica and surrounding areas
- Must remain a resident for ≥ 6 months after the first study vaccination
PATIENT CHARACTERISTICS:
Age
- 18 to 25
Performance status
•Not specified
Life expectancy
•Not specified
Hematopoietic
•Not specified
Hepatic
-
No history of chronic hepatitis requiring treatment
-
No acute or chronic clinically significant hepatic function abnormality by physical examination or laboratory findings
-
No known history of hepatitis A infection
Renal
-
No history of kidney disease requiring treatment
-
No acute or chronic clinically significant kidney function abnormality by physical examination or laboratory findings
Cardiovascular
-
No acute or chronic clinically significant cardiovascular function abnormality by physical examination or laboratory findings Pulmonary
-
No acute or chronic clinically significant pulmonary function abnormality by physical examination or laboratory findings Immunology
-
No history of allergic disease
-
No history of autoimmune disorder requiring treatment
-
No history of allergic reaction (e.g., difficulty breathing) to any vaccine
-
No suspected allergy or reaction likely to be exacerbated by a component of the study vaccines (e.g., 2-phenoxyethanol or neomycin)
-
No hypersensitivity to latex
-
No diagnosis or suspicion of any immunodeficient condition by medical history or physical examination Other
-
Not pregnant or nursing
◦No delivery within the past 3 months
-
Negative pregnancy test
-
Fertile patients must use effective contraception for 30 days before, during, and for 60 days after completion of study treatment
-
Able to speak or understand Spanish
-
Mentally competent
-
Able to undergo pelvic exam (i.e., no heavy bleeding [menstruation or otherwise] or heavy vaginal discharge)
-
No history of cancer requiring treatment
-
No history of diabetes requiring treatment
-
No history of other chronic conditions requiring treatment
-
No acute or chronic clinically significant neurologic function abnormality by physical examination or laboratory findings
-
No other acute disease
-
No fever ≥ 37.5º C
PRIOR CONCURRENT THERAPY:
Biologic therapy
-
More than 6 months since prior chronic administration (i.e., > 14 days) of immune-modulating drugs
-
More than 90 days since prior immunoglobulins
-
More than 30 days since prior and no other concurrent investigational or non-registered vaccines
-
More than 30 days since prior registered vaccines
-
More than 8 days since prior routine meningococcal, hepatitis B, influenza, or diphtheria/tetanus vaccine
-
No prior vaccination against hepatitis A
-
No prior vaccination against human papillomavirus
-
No prior monophosphoryl lipid A or AS04 adjuvant
Chemotherapy
•Not specified
Endocrine therapy
-
More than 6 months since prior chronic administration (i.e., > 14 days) of corticosteroids (e.g., ≥ 0.5 mg/kg/day of prednisone or equivalent)
-
Concurrent inhaled or topical steroids allowed
Radiotherapy
•Not specified
Surgery
•No prior hysterectomy
Other
-
More than 6 months since prior chronic administration (i.e., > 14 days) of immunosuppressants
-
More than 30 days since prior and no other concurrent investigational or non-registered drugs
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Proyecto Epidemiologico Guanacaste | Liberia | Costa Rica |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
- Kemp TJ, Hildesheim A, Safaeian M, Dauner JG, Pan Y, Porras C, Schiller JT, Lowy DR, Herrero R, Pinto LA. HPV16/18 L1 VLP vaccine induces cross-neutralizing antibodies that may mediate cross-protection. Vaccine. 2011 Mar 3;29(11):2011-4. doi: 10.1016/j.vaccine.2011.01.001. Epub 2011 Jan 15.
- Kreimer AR, Rodriguez AC, Hildesheim A, Herrero R, Porras C, Schiffman M, González P, Solomon D, Jiménez S, Schiller JT, Lowy DR, Quint W, Sherman ME, Schussler J, Wacholder S; CVT Vaccine Group. Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine. J Natl Cancer Inst. 2011 Oct 5;103(19):1444-51. doi: 10.1093/jnci/djr319. Epub 2011 Sep 9.
- CDR0000441189
- NCI-04-C-N191
- NCI-590299/009
- GSK-590299/009
- NCT00344357
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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 subjects received both vaccines and were included in the denominator of both arm based on the actual vaccine type administered. |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Period Title: Overall Study | ||
| STARTED | 3727 | 3739 |
| COMPLETED | 3453 | 3481 |
| NOT COMPLETED | 274 | 258 |
Baseline Characteristics
| Arm/Group Title | Cervarix Group | Havrix Group | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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 of all reporting groups |
| Overall Participants | 3727 | 3739 | 7466 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Years |
21.1
(2.3)
|
21.1
(2.3)
|
21.1
(2.3)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
3727
100%
|
3739
100%
|
7466
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen. |
|---|---|
| Description | CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer. Preceding cervical cytology means the last cervical cytology specimen collected before the histopathology specimen was obtained. Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) by polymerase chain reaction (PCR) at Month 0 and Month 6 for the corresponding HPV-type. |
| Time Frame | From Month 6 up to Month 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6). |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 2635 | 2677 |
| HPV16 Associated CIN2+ (N=2464;2452) |
1
|
9
|
| HPV18 Associated CIN2+ (N=2567; 2593) |
0
|
2
|
| HPV16 and/or 18 Associated CIN2+ (N=2635;2677) |
1
|
10
|
| Title | Number of Cervical Infection With HPV16 or HPV18. |
|---|---|
| Description | Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type |
| Time Frame | From Month 6 up to Month 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6). |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 2635 | 2677 |
| HPV16 Cervical Infection (N=2464;2452) |
50
|
251
|
| HPV18 Cervical Infection (N=2567;2593) |
32
|
177
|
| HPV16 and/or 18 Cervical Infection (N=2635;2677) |
78
|
387
|
| Title | Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type |
|---|---|
| Description | Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 detected by polymerase chain reaction (PRC) in the preceding cervical cytology specimen. Note: The assay did not distinguish between HPV types 68 and 73. CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type |
| Time Frame | From Month 6 up to Month 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6). |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 2643 | 2697 |
| HPV16 Associated CIN2+ (N=2464;2452) |
1
|
9
|
| HPV18 Associated CIN2+ (N=2567,2593) |
0
|
2
|
| HPV31 Associated CIN2+ (N=2525;2546) |
1
|
6
|
| HPV33 Associated CIN2+ (N=2596;2645) |
0
|
3
|
| HPV35 Associated CIN2+ (N=2593;2631) |
0
|
4
|
| HPV39 Associated CIN2+ (N=2528;2581) |
0
|
0
|
| HPV45 Associated CIN2+ (N=2573;2622) |
1
|
1
|
| HPV51 Associated CIN2+ (N=2453;2539) |
1
|
6
|
| HPV52 Associated CIN2+ (N=2456;2505) |
5
|
10
|
| HPV56 Associated CIN2+ (N=2524;2564) |
1
|
5
|
| HPV58 Associated CIN2+ (N=2551;2595) |
2
|
5
|
| HPV59 Associated CIN2+ (N=2576;2637) |
3
|
3
|
| HPV68 and/or 73 Associated CIN2+ (N=2519;2576) |
1
|
4
|
| Non 16/18 Onco HPV Associated CIN2+ (N=2643;2697) |
11
|
28
|
| Any Oncogenic HPV Associated CIN2+ (N=2643;2697) |
11
|
33
|
| Title | Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases |
|---|---|
| Description | Persistent incident HPV-16 and /or HPV-18 cervical infection had to fulfil the following criteria: first detection after the 6-month visit, 2 same type HPV positive (by PCR) test results 10+ months apart, and no intervening HPV negative tests for the corresponding type. Persistent HPV16 or HPV18 cervical infection = detection of the same HPV type by polymerase chain reaction (PCR) in cervical samples from all consecutive evaluations over approximately 12 months. Subjects were HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type. |
| Time Frame | From Month 6 up to Month 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6). |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 2635 | 2677 |
| Persistent HPV16 Infection (N=2464,2452) |
10
|
71
|
| Persistent HPV18 Infection (N=2567;2593) |
0
|
37
|
| Persistent HPV16 and/or 18 Infection (N=2635;2677) |
10
|
104
|
| Title | Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort. |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 196 | 157 |
| HPV-16 [before vaccination] (N=194;156) |
6.7
|
8.2
|
| HPV-16 [at Month 1] (N=196,157) |
646.6
|
7.9
|
| HPV-16 [at Month 6] (N=195,156) |
771.5
|
8.4
|
| HPV-16 [at Month 7] (N=195,157) |
3261
|
8.5
|
| HPV-16 [at Month 12] (N=182,146) |
2090
|
8.3
|
| HPV-16 [at Month 18] (N=25,17) |
1045
|
10.4
|
| HPV-16 [at Month 24] (N=175,137) |
1486
|
8.6
|
| HPV-16 [at Month 30] (N=19,15) |
1070
|
11.9
|
| HPV-16 [at Month 36] (N=163,132) |
1256
|
9.0
|
| HPV-16 [at Month 42] (N=22,18) |
1259
|
6.1
|
| HPV-16 [at Month 48] (N=172,131) |
1155
|
9.5
|
| Title | Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort |
|---|---|
| Description | Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohortby Enzyme linked immunosorbent assay (ELISA) and expressed as geometric mean titers (GMTs). Seronegative (Sero-) subjects=antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects=antibody concentration equal to or above 7 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 203 | 175 |
| HPV-18 [before vaccination] (N=200;173) |
5.4
|
6.2
|
| HPV-18 [at Month 1] (N=203;170) |
372.7
|
6.4
|
| HPV-18 [at Month 6] (N=203;175) |
532.2
|
6.7
|
| HPV-18 [at Month 7] (N=202;175) |
3276
|
6.8
|
| HPV-18 [at Month 12] (N=190;166) |
1082
|
7.0
|
| HPV-18 [at Month 18] (N=28;20) |
502.4
|
6.7
|
| HPV-18 [at Month 24] (N=178;150) |
633.0
|
6.9
|
| HPV-18 [at Month 30] (N=17;19) |
403.8
|
6.4
|
| HPV-18 [at Month 36] (N=168;145) |
519.7
|
6.0
|
| HPV-18 [at Month 42] (N=25;19) |
582.4
|
5.5
|
| HPV-18 [at Month 48] (N=179;149) |
470.1
|
6.6
|
| Title | HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test) |
|---|---|
| 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 41 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects=antibody concentration equal to or above 41 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 196 | 158 |
| HPV-16 [before vaccination] (N=196;158) |
21.1
|
21.4
|
| HPV-16 [at Month 1] (N=182;155) |
58.5
|
21.5
|
| HPV-16 [at Month 6] (N=189;156) |
80.9
|
21.5
|
| HPV-16 [at Month 7] (N=193;158) |
1047
|
21.4
|
| HPV-16 [at Month 12] (N=175;146) |
291.4
|
22.6
|
| HPV-16 [at Month 18] (N=24;17) |
116.6
|
20.5
|
| HPV-16 [at Month 24] (N=169;138) |
184.6
|
21.4
|
| HPV-16 [at Month 30] (N=18;15) |
112.4
|
20.5
|
| HPV-16 [at Month 36] (N=162;132) |
139.7
|
20.8
|
| HPV-16 [at Month 42] (N=22;18) |
126.9
|
20.5
|
| HPV-16 [at Month 48] (N=168;133) |
131.8
|
21.0
|
| Title | HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 203 | 176 |
| HPV-18 [before vaccination] (N=203;176) |
55.0
|
55.7
|
| HPV-18 [at Month 1] (N=197;173) |
99.1
|
55.3
|
| HPV-18 [at Month 6] (N=195;175) |
111.4
|
55.4
|
| HPV-18 [at Month 7] (N=198;176) |
823.6
|
55.0
|
| HPV-18 [at Month 12] (N=182;166) |
231.1
|
56.7
|
| HPV-18 [at Month 18] (N=28;20) |
121.8
|
55.0
|
| HPV-18 [at Month 24] (N=170;154) |
140.8
|
55.0
|
| HPV-18 [at Month 30] (N=17;19) |
89.5
|
55.0
|
| HPV-18 [at Month 36] (N=167;145) |
107.9
|
55.0
|
| HPV-18 [at Month 42] (N=25;19) |
103.3
|
55.0
|
| HPV-18 [at Month 48 (N=179;150) |
96.9
|
56.7
|
| Title | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. |
|---|---|
| Description | Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm). |
| Time Frame | Within 60 minutes after vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented. |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 3730 | 3740 |
| Any pain |
1627
|
1610
|
| Grade 3 pain |
25
|
20
|
| Any redness |
544
|
501
|
| Grade 3 redness > 50 mm |
0
|
2
|
| Any swelling |
207
|
201
|
| Grade 3 swelling > 50 mm |
0
|
1
|
| Title | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented. |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 3730 | 3740 |
| 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
|
| Title | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants. |
|---|---|
| Description | Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm). |
| Time Frame | From Day 3 to Day 6 after vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented. |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 380 | 376 |
| Any pain |
202
|
74
|
| Grade 3 pain |
0
|
0
|
| Any redness |
6
|
1
|
| Grade 3 redness |
1
|
0
|
| Any swelling |
23
|
1
|
| Grade 3 swelling |
7
|
0
|
| Title | Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants. |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented. |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 380 | 376 |
| 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
|
| Title | Number of Subjects Reporting Serious Adverse Events (SAEs). |
|---|---|
| Description | SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. |
| Time Frame | During the entire study period (From Month 0 up to Month 48). |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented. |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 3727 | 3739 |
| Number [Subjects] |
912
|
891
|
| Title | Number of Subjects Reporting Unsolicited Adverse Events (AEs). |
|---|---|
| Description | An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. |
| Time Frame | During the entire study period (From Month 0 up to Month 48). |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented. |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 3727 | 3739 |
| Number [Subjects] |
3228
|
3254
|
| Title | Number of Subjects With All Possible Pregnancy Outcomes |
|---|---|
| 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the Total Vaccinated Cohort, on all pregnant subjects. |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 2123 | 2129 |
| Pregnancy loss |
317
|
294
|
| Pregnancy resolved alive |
1756
|
1766
|
| Unresolved pregnancy |
50
|
69
|
| Title | Number of Cervical Infection With HPV16 or HPV18. |
|---|---|
| Description | Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type |
| Time Frame | During the first year of follow-up period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6). |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 2380 | 2420 |
| HPV16 Cervical Infection (N=2242;2232) |
21
|
37
|
| HPV18 Cervical Infection (N=2330;2347) |
7
|
29
|
| HPV16 and/or 18 Cervical Infection (N=2380;2420) |
27
|
64
|
| Title | Number of Cervical Infection With HPV16 or HPV18. |
|---|---|
| Description | Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type |
| Time Frame | During the second year of follow-up period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6). |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 2313 | 2349 |
| HPV16 Cervical Infection (N=2170;2176) |
10
|
77
|
| HPV18 Cervical Infection (N=2269;2307) |
9
|
47
|
| HPV16 and/or 18 Cervical Infection (N=2313;2349) |
18
|
117
|
| Title | Number of Cervical Infection With HPV16 or HPV18. |
|---|---|
| Description | Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type |
| Time Frame | During the third year of follow-up period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6). |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 2232 | 2196 |
| HPV16 Cervical Infection (N=2097;2026) |
6
|
60
|
| HPV18 Cervical Infection (N=2200;2196) |
6
|
44
|
| HPV16 and/or 18 Cervical Infection (N=2236;2166) |
11
|
88
|
| Title | Number of Cervical Infection With HPV16 or HPV18. |
|---|---|
| Description | Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type |
| Time Frame | From the fourth year follow-up period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6). |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 2421 | 2325 |
| HPV16 Cervical Infection (N=2277;2139) |
13
|
77
|
| HPV18 Cervical Infection (N=2389;2325) |
10
|
57
|
| HPV16 and/or 18 Cervical Infection (N=2421;2261) |
22
|
118
|
| Title | Number of Subjects Reporting Unsolicited Adverse Events (AEs). |
|---|---|
| Description | An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. |
| Time Frame | within 30 days (Days 0-29) after vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented. |
| Arm/Group Title | Cervarix Group | Havrix Group |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 3727 | 3739 |
| Number [Subjects] |
1638
|
1536
|
Adverse Events
| Time Frame | Solicited AEs: within 60 minutes after vaccination for all participants [please refer to Participant Flow Pre-assignment Details for population description]; From Day 3 to Day 6 post-vaccination for a 10% random subset of participants. 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 | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | For this study, the Total Number (#) of Participants Affected by Other (non-serious) Adverse Events (AEs) was analyzed separately for expected AEs and for unexpected AEs. A consolidated analysis of all expected and unexpected AEs was not technically possible to be performed and the relevant data are no longer available. Therefore, the Total #Participants Affected in Other Adverse Events Table is currently populated by the highest value of #Participants affected within other AE's table. | |||
| Arm/Group Title | Cervarix Group | Havrix Group | ||
| Arm/Group Description | 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. | 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. | ||
All Cause Mortality |
||||
| Cervarix Group | Havrix Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Cervarix Group | Havrix Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 912/3727 (24.5%) | 891/3739 (23.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia of pregnancy | 24/3727 (0.6%) | 22/3739 (0.6%) | ||
| Lymphadenitis | 2/3727 (0.1%) | 1/3739 (0%) | ||
| Blood disorder | 1/3727 (0%) | 1/3739 (0%) | ||
| Anaemia | 0/3727 (0%) | 1/3739 (0%) | ||
| Anaemia haemolytic autoimmune | 1/3727 (0%) | 0/3739 (0%) | ||
| Haemorrhagic anaemia | 1/3727 (0%) | 0/3739 (0%) | ||
| Haemorrhagic disorder | 0/3727 (0%) | 1/3739 (0%) | ||
| Thrombocytopenia | 0/3727 (0%) | 1/3739 (0%) | ||
| Cardiac disorders | ||||
| Cardiovascular disorder | 5/3727 (0.1%) | 0/3739 (0%) | ||
| Acute myocardial infarction | 1/3727 (0%) | 0/3739 (0%) | ||
| Congestive cardiomyopathy | 1/3727 (0%) | 0/3739 (0%) | ||
| Congenital, familial and genetic disorders | ||||
| Congenital flat feet | 0/3727 (0%) | 1/3739 (0%) | ||
| Multiple congenital abnormalities | 1/3727 (0%) | 0/3739 (0%) | ||
| Endocrine disorders | ||||
| Hyperthyroidism | 2/3727 (0.1%) | 1/3739 (0%) | ||
| Eye disorders | ||||
| Eye degenerative disorder | 1/3727 (0%) | 0/3739 (0%) | ||
| Retinal disorder | 0/3727 (0%) | 1/3739 (0%) | ||
| Strabismus | 1/3727 (0%) | 0/3739 (0%) | ||
| Ulcerative keratitis | 1/3727 (0%) | 0/3739 (0%) | ||
| Gastrointestinal disorders | ||||
| Gastrointestinal disorder | 9/3727 (0.2%) | 9/3739 (0.2%) | ||
| Pancreatitis acute | 6/3727 (0.2%) | 5/3739 (0.1%) | ||
| Abdominal pain | 6/3727 (0.2%) | 3/3739 (0.1%) | ||
| Irritable bowel syndrome | 1/3727 (0%) | 4/3739 (0.1%) | ||
| Colitis ulcerative | 2/3727 (0.1%) | 1/3739 (0%) | ||
| Appendix disorder | 2/3727 (0.1%) | 0/3739 (0%) | ||
| Constipation | 1/3727 (0%) | 1/3739 (0%) | ||
| Gastrointestinal inflammation | 1/3727 (0%) | 1/3739 (0%) | ||
| Abdominal mass | 0/3727 (0%) | 1/3739 (0%) | ||
| Abdominal pain lower | 1/3727 (0%) | 0/3739 (0%) | ||
| Abdominal pain upper | 0/3727 (0%) | 1/3739 (0%) | ||
| Crohn's disease | 1/3727 (0%) | 0/3739 (0%) | ||
| Duodenal ulcer haemorrhage | 1/3727 (0%) | 0/3739 (0%) | ||
| Femoral hernia | 0/3727 (0%) | 1/3739 (0%) | ||
| Gastritis | 1/3727 (0%) | 0/3739 (0%) | ||
| Gastrointestinal haemorrhage | 0/3727 (0%) | 1/3739 (0%) | ||
| Ileus paralytic | 1/3727 (0%) | 0/3739 (0%) | ||
| Intestinal obstruction | 0/3727 (0%) | 1/3739 (0%) | ||
| Pancreatitis chronic | 1/3727 (0%) | 0/3739 (0%) | ||
| Peritoneal adhesions | 1/3727 (0%) | 0/3739 (0%) | ||
| Peritoneal disorder | 0/3727 (0%) | 1/3739 (0%) | ||
| Tooth ankylosis | 1/3727 (0%) | 0/3739 (0%) | ||
| Tooth development disorder | 1/3727 (0%) | 0/3739 (0%) | ||
| Tooth malformation | 1/3727 (0%) | 0/3739 (0%) | ||
| General disorders | ||||
| Pyrexia | 5/3727 (0.1%) | 1/3739 (0%) | ||
| Eye complication associated with device | 1/3727 (0%) | 0/3739 (0%) | ||
| Gait disturbance | 0/3727 (0%) | 1/3739 (0%) | ||
| Hepatobiliary disorders | ||||
| Cholecystitis | 26/3727 (0.7%) | 19/3739 (0.5%) | ||
| Cholelithiasis | 22/3727 (0.6%) | 9/3739 (0.2%) | ||
| Liver disorder | 0/3727 (0%) | 3/3739 (0.1%) | ||
| Bile duct stone | 1/3727 (0%) | 0/3739 (0%) | ||
| Biliary cirrhosis | 1/3727 (0%) | 0/3739 (0%) | ||
| Biliary tract disorder | 1/3727 (0%) | 0/3739 (0%) | ||
| Immune system disorders | ||||
| Anaphylactic shock | 0/3727 (0%) | 2/3739 (0.1%) | ||
| Rhesus incompatibility | 0/3727 (0%) | 1/3739 (0%) | ||
| Infections and infestations | ||||
| Dengue fever | 38/3727 (1%) | 48/3739 (1.3%) | ||
| Urinary tract infection | 25/3727 (0.7%) | 24/3739 (0.6%) | ||
| Appendicitis | 17/3727 (0.5%) | 18/3739 (0.5%) | ||
| Postoperative wound infection | 12/3727 (0.3%) | 12/3739 (0.3%) | ||
| Postpartum sepsis | 12/3727 (0.3%) | 8/3739 (0.2%) | ||
| Subcutaneous abscess | 5/3727 (0.1%) | 5/3739 (0.1%) | ||
| Infectious peritonitis | 6/3727 (0.2%) | 2/3739 (0.1%) | ||
| Pelvic inflammatory disease | 3/3727 (0.1%) | 3/3739 (0.1%) | ||
| Cellulitis | 1/3727 (0%) | 4/3739 (0.1%) | ||
| Salpingitis | 3/3727 (0.1%) | 2/3739 (0.1%) | ||
| Staphylococcal infection | 3/3727 (0.1%) | 2/3739 (0.1%) | ||
| Bronchopneumonia | 1/3727 (0%) | 3/3739 (0.1%) | ||
| Viral infection | 1/3727 (0%) | 3/3739 (0.1%) | ||
| Amniotic cavity infection | 1/3727 (0%) | 2/3739 (0.1%) | ||
| Bartholin's abscess | 2/3727 (0.1%) | 1/3739 (0%) | ||
| Bronchitis | 2/3727 (0.1%) | 1/3739 (0%) | ||
| Sexually transmitted disease | 1/3727 (0%) | 2/3739 (0.1%) | ||
| HIV infection | 1/3727 (0%) | 1/3739 (0%) | ||
| Otitis externa | 2/3727 (0.1%) | 0/3739 (0%) | ||
| Parametritis | 1/3727 (0%) | 1/3739 (0%) | ||
| Pneumonia | 2/3727 (0.1%) | 0/3739 (0%) | ||
| Tooth abscess | 2/3727 (0.1%) | 0/3739 (0%) | ||
| Vaginal infection | 1/3727 (0%) | 1/3739 (0%) | ||
| Anal abscess | 1/3727 (0%) | 0/3739 (0%) | ||
| Breast abscess | 1/3727 (0%) | 0/3739 (0%) | ||
| Candida sepsis | 1/3727 (0%) | 0/3739 (0%) | ||
| Chronic sinusitis | 1/3727 (0%) | 0/3739 (0%) | ||
| Genital herpes | 1/3727 (0%) | 0/3739 (0%) | ||
| Genitourinary tract infection | 0/3727 (0%) | 1/3739 (0%) | ||
| Malaria | 1/3727 (0%) | 0/3739 (0%) | ||
| Mastitis postpartum | 0/3727 (0%) | 1/3739 (0%) | ||
| Meningitis viral | 1/3727 (0%) | 0/3739 (0%) | ||
| Otitis media | 0/3727 (0%) | 1/3739 (0%) | ||
| Pilonidal cyst | 1/3727 (0%) | 0/3739 (0%) | ||
| Pneumonia viral | 1/3727 (0%) | 0/3739 (0%) | ||
| Post procedural infection | 0/3727 (0%) | 1/3739 (0%) | ||
| Pyoderma | 1/3727 (0%) | 0/3739 (0%) | ||
| Skin infection | 0/3727 (0%) | 1/3739 (0%) | ||
| Syphilis | 0/3727 (0%) | 1/3739 (0%) | ||
| Varicella | 0/3727 (0%) | 1/3739 (0%) | ||
| Vulval abscess | 1/3727 (0%) | 0/3739 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Multiple injuries | 3/3727 (0.1%) | 10/3739 (0.3%) | ||
| Injury | 2/3727 (0.1%) | 5/3739 (0.1%) | ||
| Postoperative wound complication | 4/3727 (0.1%) | 3/3739 (0.1%) | ||
| Concussion | 2/3727 (0.1%) | 3/3739 (0.1%) | ||
| Lower limb fracture | 2/3727 (0.1%) | 2/3739 (0.1%) | ||
| Open wound | 3/3727 (0.1%) | 1/3739 (0%) | ||
| Humerus fracture | 3/3727 (0.1%) | 0/3739 (0%) | ||
| Toxicity to various agents | 2/3727 (0.1%) | 1/3739 (0%) | ||
| Lumbar vertebral fracture | 1/3727 (0%) | 1/3739 (0%) | ||
| Multiple fractures | 2/3727 (0.1%) | 0/3739 (0%) | ||
| Post procedural complication | 0/3727 (0%) | 2/3739 (0.1%) | ||
| Road traffic accident | 1/3727 (0%) | 1/3739 (0%) | ||
| Thermal burn | 2/3727 (0.1%) | 0/3739 (0%) | ||
| Ulna fracture | 1/3727 (0%) | 1/3739 (0%) | ||
| Venom poisoning | 0/3727 (0%) | 2/3739 (0.1%) | ||
| Chemical poisoning | 0/3727 (0%) | 1/3739 (0%) | ||
| Contusion | 1/3727 (0%) | 0/3739 (0%) | ||
| Facial bones fracture | 0/3727 (0%) | 1/3739 (0%) | ||
| Femoral neck fracture | 1/3727 (0%) | 0/3739 (0%) | ||
| Foot fracture | 1/3727 (0%) | 0/3739 (0%) | ||
| Foreign body | 1/3727 (0%) | 0/3739 (0%) | ||
| Jaw fracture | 1/3727 (0%) | 0/3739 (0%) | ||
| Muscle injury | 0/3727 (0%) | 1/3739 (0%) | ||
| Muscle strain | 0/3727 (0%) | 1/3739 (0%) | ||
| Radius fracture | 1/3727 (0%) | 0/3739 (0%) | ||
| Tendon injury | 0/3727 (0%) | 1/3739 (0%) | ||
| Tibia fracture | 0/3727 (0%) | 1/3739 (0%) | ||
| Investigations | ||||
| Medical observation | 1/3727 (0%) | 0/3739 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Gestational diabetes | 5/3727 (0.1%) | 6/3739 (0.2%) | ||
| Type 2 diabetes mellitus | 3/3727 (0.1%) | 1/3739 (0%) | ||
| Diabetic ketoacidosis | 0/3727 (0%) | 1/3739 (0%) | ||
| Hypokalaemia | 0/3727 (0%) | 1/3739 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Rheumatoid arthritis | 1/3727 (0%) | 1/3739 (0%) | ||
| Systemic lupus erythematosus | 2/3727 (0.1%) | 0/3739 (0%) | ||
| Back pain | 1/3727 (0%) | 0/3739 (0%) | ||
| Intervertebral disc displacement | 0/3727 (0%) | 1/3739 (0%) | ||
| Musculoskeletal pain | 1/3727 (0%) | 0/3739 (0%) | ||
| Myalgia | 0/3727 (0%) | 1/3739 (0%) | ||
| Tenosynovitis | 0/3727 (0%) | 1/3739 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Benign ovarian tumour | 11/3727 (0.3%) | 7/3739 (0.2%) | ||
| Thyroid cancer | 1/3727 (0%) | 3/3739 (0.1%) | ||
| Ovarian cancer | 2/3727 (0.1%) | 1/3739 (0%) | ||
| Uterine leiomyoma | 2/3727 (0.1%) | 1/3739 (0%) | ||
| Benign hydatidiform mole | 1/3727 (0%) | 1/3739 (0%) | ||
| Colon neoplasm | 0/3727 (0%) | 1/3739 (0%) | ||
| Nasal sinus cancer | 1/3727 (0%) | 0/3739 (0%) | ||
| Non-Hodgkin's lymphoma | 0/3727 (0%) | 1/3739 (0%) | ||
| Placental neoplasm | 0/3727 (0%) | 1/3739 (0%) | ||
| Vulval neoplasm | 0/3727 (0%) | 1/3739 (0%) | ||
| Nervous system disorders | ||||
| Migraine | 2/3727 (0.1%) | 1/3739 (0%) | ||
| Convulsion | 1/3727 (0%) | 1/3739 (0%) | ||
| Nervous system disorder | 0/3727 (0%) | 2/3739 (0.1%) | ||
| Tension headache | 1/3727 (0%) | 1/3739 (0%) | ||
| Autonomic nervous system imbalance | 1/3727 (0%) | 0/3739 (0%) | ||
| Complicated migraine | 0/3727 (0%) | 1/3739 (0%) | ||
| Epilepsy | 0/3727 (0%) | 1/3739 (0%) | ||
| Headache | 0/3727 (0%) | 1/3739 (0%) | ||
| Hydrocephalus | 0/3727 (0%) | 1/3739 (0%) | ||
| Intracranial hypotension | 1/3727 (0%) | 0/3739 (0%) | ||
| Vascular headache | 1/3727 (0%) | 0/3739 (0%) | ||
| Pregnancy, puerperium and perinatal conditions | ||||
| Abortion spontaneous incomplete | 134/3727 (3.6%) | 108/3739 (2.9%) | ||
| False labour | 66/3727 (1.8%) | 88/3739 (2.4%) | ||
| Abortion spontaneous complete | 64/3727 (1.7%) | 64/3739 (1.7%) | ||
| Abortion missed | 59/3727 (1.6%) | 63/3739 (1.7%) | ||
| Foetal distress syndrome | 57/3727 (1.5%) | 64/3739 (1.7%) | ||
| Uterine hypotonus | 54/3727 (1.4%) | 54/3739 (1.4%) | ||
| Gestational hypertension | 39/3727 (1%) | 53/3739 (1.4%) | ||
| Abortion threatened | 42/3727 (1.1%) | 37/3739 (1%) | ||
| Cephalo-pelvic disproportion | 33/3727 (0.9%) | 45/3739 (1.2%) | ||
| Breech presentation | 40/3727 (1.1%) | 33/3739 (0.9%) | ||
| Pre-eclampsia | 18/3727 (0.5%) | 23/3739 (0.6%) | ||
| Failed induction of labour | 19/3727 (0.5%) | 20/3739 (0.5%) | ||
| Complication of pregnancy | 18/3727 (0.5%) | 19/3739 (0.5%) | ||
| Intra-uterine death | 16/3727 (0.4%) | 18/3739 (0.5%) | ||
| Foetal growth restriction | 18/3727 (0.5%) | 14/3739 (0.4%) | ||
| Premature rupture of membranes | 11/3727 (0.3%) | 19/3739 (0.5%) | ||
| Obstructed labour | 13/3727 (0.3%) | 15/3739 (0.4%) | ||
| Abnormal product of conception | 14/3727 (0.4%) | 11/3739 (0.3%) | ||
| Ectopic pregnancy | 9/3727 (0.2%) | 14/3739 (0.4%) | ||
| Postpartum haemorrhage | 13/3727 (0.3%) | 7/3739 (0.2%) | ||
| Oligohydramnios | 11/3727 (0.3%) | 8/3739 (0.2%) | ||
| Premature separation of placenta | 5/3727 (0.1%) | 10/3739 (0.3%) | ||
| Hyperemesis gravidarum | 6/3727 (0.2%) | 8/3739 (0.2%) | ||
| Multiple pregnancy | 8/3727 (0.2%) | 2/3739 (0.1%) | ||
| Placenta praevia haemorrhage | 6/3727 (0.2%) | 4/3739 (0.1%) | ||
| Foetal disorder | 7/3727 (0.2%) | 2/3739 (0.1%) | ||
| Large for dates baby | 4/3727 (0.1%) | 4/3739 (0.1%) | ||
| Premature delivery | 5/3727 (0.1%) | 2/3739 (0.1%) | ||
| Premature labour | 2/3727 (0.1%) | 4/3739 (0.1%) | ||
| Transverse presentation | 3/3727 (0.1%) | 3/3739 (0.1%) | ||
| Abortion incomplete | 4/3727 (0.1%) | 1/3739 (0%) | ||
| Umbilical cord abnormality | 3/3727 (0.1%) | 2/3739 (0.1%) | ||
| Eclampsia | 1/3727 (0%) | 3/3739 (0.1%) | ||
| Retained placenta or membranes | 4/3727 (0.1%) | 0/3739 (0%) | ||
| Abortion complicated | 3/3727 (0.1%) | 0/3739 (0%) | ||
| Foetal malpresentation | 0/3727 (0%) | 3/3739 (0.1%) | ||
| Placenta praevia | 2/3727 (0.1%) | 1/3739 (0%) | ||
| Polyhydramnios | 1/3727 (0%) | 1/3739 (0%) | ||
| Traumatic delivery | 1/3727 (0%) | 1/3739 (0%) | ||
| Umbilical cord prolapse | 2/3727 (0.1%) | 0/3739 (0%) | ||
| Abortion incomplete complicated | 0/3727 (0%) | 1/3739 (0%) | ||
| Abortion spontaneous incomplete complicated | 0/3727 (0%) | 1/3739 (0%) | ||
| Foetal malposition | 1/3727 (0%) | 0/3739 (0%) | ||
| Intrapartum haemorrhage | 1/3727 (0%) | 0/3739 (0%) | ||
| Pelvic haematoma obstetric | 0/3727 (0%) | 1/3739 (0%) | ||
| Placental disorder | 1/3727 (0%) | 0/3739 (0%) | ||
| Post abortion haemorrhage | 0/3727 (0%) | 1/3739 (0%) | ||
| Postpartum disorder | 0/3727 (0%) | 1/3739 (0%) | ||
| Previous caesarean section | 1/3727 (0%) | 0/3739 (0%) | ||
| Prolonged labour | 0/3727 (0%) | 1/3739 (0%) | ||
| Prolonged pregnancy | 1/3727 (0%) | 0/3739 (0%) | ||
| Twin pregnancy | 0/3727 (0%) | 1/3739 (0%) | ||
| Uterine inversion | 1/3727 (0%) | 0/3739 (0%) | ||
| Psychiatric disorders | ||||
| Intentional self-injury | 20/3727 (0.5%) | 17/3739 (0.5%) | ||
| Depression | 5/3727 (0.1%) | 3/3739 (0.1%) | ||
| Mental disorder | 5/3727 (0.1%) | 3/3739 (0.1%) | ||
| Post-traumatic stress disorder | 1/3727 (0%) | 1/3739 (0%) | ||
| Acute psychosis | 1/3727 (0%) | 0/3739 (0%) | ||
| Drug dependence | 0/3727 (0%) | 1/3739 (0%) | ||
| Emotional disorder | 1/3727 (0%) | 0/3739 (0%) | ||
| Psychotic disorder | 1/3727 (0%) | 0/3739 (0%) | ||
| Renal and urinary disorders | ||||
| Calculus urinary | 1/3727 (0%) | 2/3739 (0.1%) | ||
| Tubulointerstitial nephritis | 2/3727 (0.1%) | 1/3739 (0%) | ||
| Nephrolithiasis | 2/3727 (0.1%) | 0/3739 (0%) | ||
| Proteinuria | 2/3727 (0.1%) | 0/3739 (0%) | ||
| Calculus ureteric | 1/3727 (0%) | 0/3739 (0%) | ||
| Haematuria | 1/3727 (0%) | 0/3739 (0%) | ||
| Reproductive system and breast disorders | ||||
| Ovarian cyst | 5/3727 (0.1%) | 6/3739 (0.2%) | ||
| Uterine haemorrhage | 5/3727 (0.1%) | 5/3739 (0.1%) | ||
| Menometrorrhagia | 5/3727 (0.1%) | 2/3739 (0.1%) | ||
| Vaginal haemorrhage | 3/3727 (0.1%) | 4/3739 (0.1%) | ||
| Breast inflammation | 2/3727 (0.1%) | 2/3739 (0.1%) | ||
| Endometriosis | 2/3727 (0.1%) | 2/3739 (0.1%) | ||
| Pelvic pain | 1/3727 (0%) | 3/3739 (0.1%) | ||
| Perineal pain | 1/3727 (0%) | 3/3739 (0.1%) | ||
| Genital disorder female | 1/3727 (0%) | 2/3739 (0.1%) | ||
| Menstruation irregular | 1/3727 (0%) | 2/3739 (0.1%) | ||
| Bartholin's cyst | 1/3727 (0%) | 1/3739 (0%) | ||
| Cervix disorder | 2/3727 (0.1%) | 0/3739 (0%) | ||
| Uterine polyp | 1/3727 (0%) | 1/3739 (0%) | ||
| Amenorrhoea | 1/3727 (0%) | 0/3739 (0%) | ||
| Breast disorder | 1/3727 (0%) | 0/3739 (0%) | ||
| Breast enlargement | 1/3727 (0%) | 0/3739 (0%) | ||
| Cervical dysplasia | 0/3727 (0%) | 1/3739 (0%) | ||
| Haematocolpos | 0/3727 (0%) | 1/3739 (0%) | ||
| Haematosalpinx | 1/3727 (0%) | 0/3739 (0%) | ||
| Ovarian torsion | 0/3727 (0%) | 1/3739 (0%) | ||
| Ovulation pain | 0/3727 (0%) | 1/3739 (0%) | ||
| Polycystic ovaries | 0/3727 (0%) | 1/3739 (0%) | ||
| Polymenorrhagia | 1/3727 (0%) | 0/3739 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Respiratory disorder | 5/3727 (0.1%) | 2/3739 (0.1%) | ||
| Asthma | 2/3727 (0.1%) | 0/3739 (0%) | ||
| Status asthmaticus | 2/3727 (0.1%) | 0/3739 (0%) | ||
| Bronchitis chronic | 1/3727 (0%) | 0/3739 (0%) | ||
| Dyspnoea | 1/3727 (0%) | 0/3739 (0%) | ||
| Neonatal respiratory failure | 0/3727 (0%) | 1/3739 (0%) | ||
| Pleural effusion | 1/3727 (0%) | 0/3739 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Urticaria | 0/3727 (0%) | 2/3739 (0.1%) | ||
| Granuloma skin | 0/3727 (0%) | 1/3739 (0%) | ||
| Skin disorder | 0/3727 (0%) | 1/3739 (0%) | ||
| Toxic skin eruption | 0/3727 (0%) | 1/3739 (0%) | ||
| Social circumstances | ||||
| Physical assault | 3/3727 (0.1%) | 0/3739 (0%) | ||
| Sexual abuse | 1/3727 (0%) | 0/3739 (0%) | ||
| Surgical and medical procedures | ||||
| Caesarean section | 56/3727 (1.5%) | 59/3739 (1.6%) | ||
| Therapeutic procedure | 0/3727 (0%) | 1/3739 (0%) | ||
| Vascular disorders | ||||
| Hypertension | 5/3727 (0.1%) | 6/3739 (0.2%) | ||
| Essential hypertension | 4/3727 (0.1%) | 1/3739 (0%) | ||
| Circulatory collapse | 2/3727 (0.1%) | 1/3739 (0%) | ||
| Phlebitis | 0/3727 (0%) | 2/3739 (0.1%) | ||
| Varicose vein | 0/3727 (0%) | 2/3739 (0.1%) | ||
| Embolism venous | 0/3727 (0%) | 1/3739 (0%) | ||
| Varicophlebitis | 0/3727 (0%) | 1/3739 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Cervarix Group | Havrix Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1627/3730 (43.6%) | 1610/3740 (43%) | ||
| Gastrointestinal disorders | ||||
| Gastrointestinal inflammation | 263/3727 (7.1%) | 249/3739 (6.7%) | ||
| General disorders | ||||
| Pain | 1627/3730 (43.6%) | 1610/3740 (43%) | ||
| Redness | 544/3730 (14.6%) | 501/3740 (13.4%) | ||
| Swelling | 207/3730 (5.5%) | 201/3740 (5.4%) | ||
| Fatigue | 512/3730 (13.7%) | 502/3740 (13.4%) | ||
| Myalgia | 257/3730 (6.9%) | 232/3740 (6.2%) | ||
| Gastrointestinal | 191/3730 (5.1%) | 171/3740 (4.6%) | ||
| Headache | 714/3730 (19.1%) | 718/3740 (19.2%) | ||
| Fever | 472/3730 (12.7%) | 477/3740 (12.8%) | ||
| Pain | 202/380 (53.2%) | 74/376 (19.7%) | ||
| Swelling | 23/380 (6.1%) | 1/376 (0.3%) | ||
| Fatigue | 214/380 (56.3%) | 189/376 (50.3%) | ||
| Myalgia | 250/380 (65.8%) | 211/376 (56.1%) | ||
| Arthralgia | 44/380 (11.6%) | 32/376 (8.5%) | ||
| Gastrointestinal | 157/380 (41.3%) | 119/376 (31.6%) | ||
| Headache | 247/380 (65%) | 242/376 (64.4%) | ||
| Rash | 31/380 (8.2%) | 26/376 (6.9%) | ||
| Fever | 43/380 (11.3%) | 37/376 (9.8%) | ||
| Infections and infestations | ||||
| Influenza | 263/3727 (7.1%) | 293/3739 (7.8%) | ||
| Influenza | 903/3727 (24.2%) | 950/3739 (25.4%) | ||
| Vaginal infection | 709/3727 (19%) | 763/3739 (20.4%) | ||
| Vulvovaginal candidiasis | 714/3727 (19.2%) | 678/3739 (18.1%) | ||
| Urinary tract infection | 555/3727 (14.9%) | 565/3739 (15.1%) | ||
| Upper respiratory tract infection | 324/3727 (8.7%) | 327/3739 (8.7%) | ||
| Dengue fever | 174/3727 (4.7%) | 190/3739 (5.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Myalgia | 355/3727 (9.5%) | 166/3739 (4.4%) | ||
| Myalgia | 386/3727 (10.4%) | 189/3739 (5.1%) | ||
| Nervous system disorders | ||||
| Headache | 218/3727 (5.8%) | 214/3739 (5.7%) | ||
| Headache | 324/3727 (8.7%) | 315/3739 (8.4%) | ||
| Reproductive system and breast disorders | ||||
| Menstruation irregular | 1021/3727 (27.4%) | 1011/3739 (27%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 |
- CDR0000441189
- NCI-04-C-N191
- NCI-590299/009
- GSK-590299/009
- NCT00344357