Study to Evaluate the Efficacy of the Human Papillomavirus Vaccine in Healthy Adult Women of 26 Years of Age and Older

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00294047
First received: February 17, 2006
Last updated: March 27, 2014
Last verified: March 2014
Results First Received: December 8, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition: Infections, Papillomavirus
Interventions: Biological: Cervarix
Biological: Placebo control

  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
Some subjects completed the study at Month 36 since they did not want to participate to the one-year extension up to Month 48. The number of subjects who participated up to Month 48 in the Cervarix Group = 2305 (80.0%) and in the Aluminium Hydroxide Group = 2281 (79.4%).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Enrolment was stratified by (1) age, with the majority of subjects in age strata 26 – 35 years and 36 – 45 years (about 45% each) and about 10% in the age stratum 46+ years, and (2) previous HPV history (in each age stratum, the number of women with a history of HPV infection/treatment was limited to approximately 15%).

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix™ vaccine. Cervarix vaccine was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.
Aluminium Hydroxide Group Subjects received 3 doses of Aluminium Hydroxide [Al(OH)3]. Aluminium Hydroxide was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.

Participant Flow:   Overall Study
    Cervarix Group     Aluminium Hydroxide Group  
STARTED     2881     2871  
COMPLETED     2456 [1]   2438 [2]
NOT COMPLETED     425     433  
Adverse Event                 28                 13  
Protocol Violation                 4                 4  
Withdrawal by Subject                 111                 115  
Lost to Follow-up                 272                 287  
Unspecified                 10                 14  
[1] The number of subjects who participated up to Month 48 in the Cervarix Group = 2305
[2] The number of subjects who participated up to Month 48 in the Aluminium Hydroxide Group = 2281



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix™ vaccine. Cervarix vaccine was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.
Aluminium Hydroxide Group Subjects received 3 doses of Aluminium Hydroxide [Al(OH)3]. Aluminium Hydroxide was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.
Total Total of all reporting groups

Baseline Measures
    Cervarix Group     Aluminium Hydroxide Group     Total  
Number of Participants  
[units: participants]
  2881     2871     5752  
Age  
[units: Years]
Mean ± Standard Deviation
     
Years     37.0  ± 7.24     37.0  ± 7.32     37.0  ± 7.28  
Gender  
[units: Subjects]
     
Female     2881     2871     5752  
Male     0     0     0  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection.   [ Time Frame: Up to Month 48 ]

2.  Primary:   Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 and/or With Histopathologically-CIN1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the HPV Type Assignment Algorithm (TAA).   [ Time Frame: Up to Month 48 ]

3.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18   [ Time Frame: Up to Month 48 ]

4.  Secondary:   Number of Subjects With Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18   [ Time Frame: Up to Month 48 ]

5.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types Individually or in Combinations.   [ Time Frame: Up to Month 48 ]

6.  Secondary:   Number of Subjects With Persistent Infection (12-month Definition) With Oncogenic HPV Types Individually or in Combinations.   [ Time Frame: Up to Month 48 ]

7.  Secondary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to Month 48 ]

8.  Secondary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to Month 48 ]

9.  Secondary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to Month 48 ]

10.  Secondary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Irrespective of HPV Cervical Infection and Irrespective of Baseline HPV DNA Status   [ Time Frame: Up to Month 48 ]

11.  Secondary:   Number of Subjects With Any Cytological Abnormalities Associated With HPV-16 or HPV-18 Cervical Infection   [ Time Frame: Up to Month 48 ]

12.  Secondary:   Number of Subjects With Cytological Abnormalities Associated With Oncogenic HPV Types Individually or in Combinations   [ Time Frame: Up to Month 48 ]

13.  Secondary:   Number of Subjects With Histopathologically Confirmed Reduction of Local Cervical Therapy   [ Time Frame: Up to Month 48 ]

14.  Secondary:   Number of Subjects With First Colposcopy   [ Time Frame: Up to Month 48 ]

15.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection   [ Time Frame: Up to Month 48 ]

16.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 and/or With Histopathologically-confirmed CIN1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the HPV Type Assignment Algorithm (TAA).   [ Time Frame: Up to Month 48 ]

17.  Secondary:   Number of Seroconverted Subjects Against HPV-16 in the Immunogenicity Subset.   [ Time Frame: At pre-vaccination and at Month 7, 12, 18, 24, 36 and 48 ]

18.  Secondary:   Number of Seroconverted Subjects Against HPV-18 in the Immunogenicity Subset.   [ Time Frame: At pre-vaccination and at Month 7, 12, 18, 24, 36 and 48 ]

19.  Secondary:   Geometric Mean Concentrations (GMCs) Against HPV-16 Antibody in the Immunogenicity Subset.   [ Time Frame: At pre-vaccination and at Month 7, 12, 18, 24, 36 and 48 ]

20.  Secondary:   Geometric Mean Concentrations (GMCs) Against HPV-18 Antibody in the Immunogenicity Subset.   [ Time Frame: At pre-vaccination and at Month 7, 12, 18, 24, 36 and 48 ]

21.  Secondary:   Number of Seroconverted Subjects Against HPV-16 and HPV-18 Viral Neutralization in a Selected Subset of Subjects.   [ Time Frame: Prior to vaccination and at Month 7, 12, 18, 24 and 48. ]

22.  Secondary:   Geometric Mean Titers (GMTs) Against HPV-16 and HPV-18 Viral Neutralization Antibodies in a Selected Subset of Subjects.   [ Time Frame: Prior to vaccination and at Month 7, 12, 18, 24 and 48. ]

23.  Secondary:   Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.   [ Time Frame: Within 7 days (Days 0-6) after vaccination ]

24.  Secondary:   Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.   [ Time Frame: Within 7 days (Days 0-6) after vaccination ]

25.  Secondary:   Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs).   [ Time Frame: Within 30 days (Days 0 – 29) post-vaccination period. ]

26.  Secondary:   Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs).   [ Time Frame: Up to Month 48 ]

27.  Secondary:   Number of Subjects Reporting New Onset of Chronic Disease (NOCDs).   [ Time Frame: Up to Month 48 ]

28.  Secondary:   Number of Subjects Reporting New Onset of Autoimmune Disease (NOADs).   [ Time Frame: Up to Month 48 ]

29.  Secondary:   Number of Subjects Reporting Medically Significant Conditions (MAEs).   [ Time Frame: Up to Month 48 ]

30.  Secondary:   Number of Subjects With Pregnancies and Their Outcomes.   [ Time Frame: Up to Month 48 ]

31.  Secondary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the Type Assignment Algorithm (TAA)   [ Time Frame: Up to Month 48 ]

32.  Secondary:   Number of Seroconverted Subjects Against HPV-16 and HPV-18 in the Immunogenicity Subset.   [ Time Frame: At Month 60, 72 and 84 ]
Results not yet posted.   Anticipated Posting Date:   12/2013   Safety Issue:   No

33.  Secondary:   Geometric Mean Concentrations (GMCs) Against HPV-16 and HPV-18 Antibodies in the Immunogenicity Subset.   [ Time Frame: At Month 60, 72 and 84 ]
Results not yet posted.   Anticipated Posting Date:   12/2013   Safety Issue:   No

34.  Secondary:   Number of Seroconverted Subjects Against HPV-16/18 in Vaccine Recipients With Breakthrough HPV-16 and/or HPV-18 Persistent Infections and HPV-16 and/or HPV-18 Associated CIN1+ Lesions.   [ Time Frame: Up to Month 84 ]
Results not yet posted.   Anticipated Posting Date:   12/2013   Safety Issue:   No

35.  Secondary:   GMTs Against HPV-16/18 Antibodies in Vaccine Recipients With Breakthrough HPV-16 and/or HPV-18 Persistent Infections and HPV-16 and/or HPV-18 Associated CIN1+ Lesions.   [ Time Frame: Up to Month 84 ]
Results not yet posted.   Anticipated Posting Date:   12/2013   Safety Issue:   No

36.  Secondary:   Number of Seroconverted Subjects Against HPV-16 and HPV-18 (V5/J4 Monoclonal Inhibition Test).   [ Time Frame: Up to Month 84 ]
Results not yet posted.   Anticipated Posting Date:   12/2013   Safety Issue:   No

37.  Secondary:   HPV-16 and HPV-18 Geometric Mean Titers (GMTs) (V5/J4 Monoclonal Inhibition Test).   [ Time Frame: Up to Month 84 ]
Results not yet posted.   Anticipated Posting Date:   12/2013   Safety Issue:   No

38.  Secondary:   Number of Seroconverted Subjects Against HPV-16 and HPV-18 Viral Neutralization.   [ Time Frame: Up to Month 84 ]
Results not yet posted.   Anticipated Posting Date:   12/2013   Safety Issue:   No

39.  Secondary:   Geometric Mean Titers (GMTs) Against HPV-16 and HPV-18 Viral Neutralization Antibodies.   [ Time Frame: Up to Month 84 ]
Results not yet posted.   Anticipated Posting Date:   12/2013   Safety Issue:   No

40.  Secondary:   Number of Subjects Reporting Related or Fatal Serious Adverse Event.   [ Time Frame: Up to Month 84 ]
Results not yet posted.   Anticipated Posting Date:   12/2013   Safety Issue:   No

41.  Secondary:   Number of Subjects Reporting Any AE/SAE Leading to Premature Discontinuation of the Study.   [ Time Frame: Up to Month 84 ]
Results not yet posted.   Anticipated Posting Date:   12/2013   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications:
Skinner R et al. HPV-16/18 AS04-Adjuvanted vaccine efficacy in ≥26-year-old women after 4-year follow-up. Abstract presented in the 27th International Papillomavirus Conference and Clinical Workshop (IPV). Berlin, Germany, 17-22 September 2011.
Descamps D et al. (2009) Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: A pooled analysis of 11 clinical trials. Hum Vaccin. 5(5):51-59.
Skinner R et al. Effect of HPV type on risk of progression from HPV infection to CIN1+ and CIN2+ in women aged 26 years and over. Abstract presented at the 28th International Papillomavirus Conference and Clinical Workshop (IPC & CW), San Juan, Puerto Rico, 30 Nov - 06 Dec 2012.


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00294047     History of Changes
Other Study ID Numbers: 104820
Study First Received: February 17, 2006
Results First Received: December 8, 2011
Last Updated: March 27, 2014
Health Authority: Peru: Instituto Nacional de Salud
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Portugal: Infarmed - Autoridade Nacional do Medicamento e Produtos de Saúde, I.P.
Mexico: Ministry of Health - Secretaria de Salud - Comisión de Autorización Sanitaria - Comisión Federal para la Protección cotnra riesgos de salud
Russian Federation: Federal service on surveillance in healthcare and social development of Russian Federation
Singapore: Health Sciences Authority
Canada: Biologics and Genetics Therapeutic Directorate (B>D)
Thailand: The Ethical Review Committee for Research in Human Subjects, Ministry of Public health
Philippines: Bureau of Food and Drugs
United States: Food and Drug Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Australia: Therapeutic Goods Administration