Human Papilloma Virus (HPV) Vaccine Efficacy Trial Against Cervical Pre-cancer in Young Adults With GlaxoSmithKline (GSK) Biologicals HPV-16/18

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00122681
First received: July 20, 2005
Last updated: July 11, 2013
Last verified: February 2012
Results First Received: November 30, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Conditions: Human Papillomavirus (HPV) Infection
Cervical Neoplasia
Interventions: Biological: Cervarix™
Biological: Havrix™-based investigational formulation

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 18729 subjects enrolled in the study, 64 subjects were not vaccinated. Within the 18665 subjects vaccinated, 21 subjects from 1 center were excluded from all analyses because of potential data discrepancies identified at this center. As a result, a total of 18644 subjects are reported as started in the participant flow.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Participant Flow:   Overall Study
    Havrix Group     Cervarix Group  
STARTED     9325     9319  
COMPLETED     7811     7798  
NOT COMPLETED     1514     1521  
Adverse Event                 20                 16  
Lost to Follow-up                 1080                 1097  
Protocol Violation                 7                 10  
Withdrawal by Subject                 257                 251  
Personal reasons                 150                 147  



  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
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.
Total Total of all reporting groups

Baseline Measures
    Havrix Group     Cervarix Group     Total  
Number of Participants  
[units: participants]
  9325     9319     18644  
Age  
[units: years]
Mean ± Standard Deviation
  20.0  ± 3.12     20.0  ± 3.10     20.0  ± 3.11  
Gender  
[units: subjects]
     
Female     9325     9319     18644  
Male     0     0     0  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post-dose 3 ]

2.  Primary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection   [ Time Frame: at Month 48 ]

3.  Secondary:   Number of Subjects Reporting Solicited Local and General Symptoms   [ Time Frame: Within 7 days after any vaccination ]

4.  Secondary:   Number of Subjects Reporting Unsolicited Adverse Events   [ Time Frame: Within 30 days after any vaccination ]

5.  Secondary:   Number of Subjects Reporting Serious Adverse Events (SAEs)   [ Time Frame: Throughout the entire study period (Month 0 to Month 48) ]

6.  Secondary:   Number of Subjects Reporting New Onset of Chronic Disease (NOCDs)   [ Time Frame: Throughout the entire study (Month 0 to 48) ]

7.  Secondary:   Number of Subjects Reporting Medically Significant Conditions   [ Time Frame: Throughout entire study period (Month 0 to Month 48) ]
  Hide Outcome Measure 7

Measure Type Secondary
Measure Title Number of Subjects Reporting Medically Significant Conditions
Measure Description Medically significant conditions include adverse events (AEs) prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
Time Frame Throughout entire study period (Month 0 to Month 48)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the Total Vaccinated Cohort and stratified according to initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
    Havrix Group     Cervarix Group  
Number of Participants Analyzed  
[units: participants]
  9325     9319  
Number of Subjects Reporting Medically Significant Conditions  
[units: subjects]
   
Total (n=9325, 9319)     3378     3298  
sero+ DNA+ (n= 2419, 2409)     957     958  
sero- DNA- (n= 6789, 6804)     2378     2303  
DNA+ (n= 649, 690)     285     296  

No statistical analysis provided for Number of Subjects Reporting Medically Significant Conditions



8.  Secondary:   Number of Subjects With Outcome of Pregnancies, Overall and Stratified by Initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus   [ Time Frame: Throughout the entire study period (Month 0 to Month 48) ]

9.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

10.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18   [ Time Frame: at Month 48 ]

11.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

12.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types   [ Time Frame: at Month 48 ]

13.  Secondary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

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

15.  Secondary:   Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

16.  Secondary:   Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18   [ Time Frame: at Month 48 ]

17.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

18.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: at Month 48 ]

19.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

20.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: at Month 48 ]

21.  Secondary:   Number of Seropositive Subjects for Anti-HPV-16 and Anti-HPV-18 Antibody Titers by ELISA in the Immunogenicity Subset, According to Initial (Month 0) HPV-16 or HPV-18 Serostatus   [ Time Frame: At Months 6, 7, 12, 24, 36 & 48 ]

22.  Secondary:   Anti-HPV-16 and Anti-HPV-18 ELISA Titers in the Immunogenicity Subset   [ Time Frame: At Months 6, 7, 12, 24, 36 and 48 ]

23.  Secondary:   HPV-16 and HPV-18 Seroconversion (V5/J4 Monoclonal Inhibition Test)   [ Time Frame: Month 0, 7, 12 and 24 ]

24.  Secondary:   HPV-16 and HPV-18 Geometric Mean Titers (GMT) (V5/J4 Monoclonal Inhibition Test)   [ Time Frame: Month 0, 7, 12, 24 ]

25.  Secondary:   Number of Subjects Seropositive for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)   [ Time Frame: At Month 0, 7, 12, 24, 36 and 48 ]

26.  Secondary:   Titers for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)   [ Time Frame: At month 0, 7, 12, 24, 36 and 48 ]


  Serious Adverse Events


  Other Adverse Events


  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.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


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


Publications:
Wacholder S et al. (2010) Risk of miscarriage with bivalent vaccine against human papillomavirus (HPV) types 16 and 18: pooled analysis of two randomised controlled trials. BMJ. 340:c712.
Kitchener H et al. Cross-protective efficacy of the AS04-adjuvanted HPV-16/18 vaccine in oncogenic HPV infection-naïve women: results from a double-blind, randomised, Phase III trial (PATRICIA). Abstract presented at the 16th International Meeting of European Society of Gynaecological Oncology. Belgrade, Serbia, 11-14 October 2009.
Tjalma W et al. Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against abnormal cytology and low-grade histopathological lesions in an oncogenic HPV-naïve population. Abstract presented at the 16th International Meeting of European Society of Gynaecological Oncology. Belgrade, Serbia, 11-14 October 2009.
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.
Romanowski B et al. Clinical benefit of the AS04-adjuvanted human papillomavirus 16/18 vaccine against CIN2+ related to the 5 most common oncogenic HPV types: PATRICIA trial. Abstract presented at IDSA. Philadelphia, USA, 29 October-1 November, 2009.
Skinner R. S et al. Cross-protective efficacy of Cervarix™ against oncogenic HPV types beyond HPV-16/18. Abstract presented at International Papillomavirus Conference and Clinical Workshop (IPvC). Malmo, Sweden, 8-14 May 2009.
Coursaget P et al. (2011) Priming as a basis for long-term protection and implications for HPV vaccination. Gynecologic Oncology. 121:S1-S9.
Paavonen J et al for the PATRICIA study group. End-of-study results of PATRICIA: A phase III efficacy study of HPV-16/18 AS04-adjuvanted vaccine in young women. Abstract presented at 26th Annual International Papillomavirus Conference and Clinical Workshop (IPV). Montreal, Québec, Canada from July 3-8, 2010.
Poppe W et al. Vaccine efficacy in women with evidence of prior HPV-16/18 infection and incomplete protection by natural immunity: analysis from a Phase III, double blind, randomised trial of the AS04-adjuvanted HPV-16/18 vaccine. Abstract presented at the 16th International Meeting of European Society of Gynaecological Oncology. Belgrade, Serbia, 11-14 October 2009.
Naud P et al. Cross-protective efficacy of the ASO4-adjuvanted HPV-16/18 vaccine against oncogenic HPV-31, -33 and -45. Abstract presented at European Research Organization on Genital Infection and Neoplasia 2010 (EUROGIN). Monte Carlo, Monaco, 17-20 February 2010.
Huh WK et al for the PATRICIA study group. Efficacy of the HPV-16/18 AS04-adjuvanted vaccine in women according to their initial dna and serostatus: PATRICIA end-of-study results. Abstract presented at International Gynecologic Cancer Society - 13th Biennial Meeting (IGCS), Prague, Czech Republic, October 23-26, 2010.
Wheeler C et al. Cross-protective efficacy of the AS04-adjuvanted human papillomavirus (HPV)-16/18 vaccine against cervical intraepithelial neoplasia 2+ in a Phase III, double-blind, randomised trial (PATRICIA). Abstract presented at the 16th International Meeting of European Society of Gynaecological Oncology. Belgrade, Serbia, 11-14 October 2009.
Chow SN et al. Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against abnormal cytology and reduction in colposcopy referrals and cervical excisions in an HPV-negative population. Abstract presented at the 16th International Meeting of European Society of Gynaecological Oncology. Belgrade, Serbia, 11-14 October 2009.
Szarewski A et al. Cross-protective efficacy of CervarixTM against oncogenic types beyond HPV-16/18 : analysis of the According-to-Protocol (ATP) cohort in a double blind, randomized controlled Phase III efficacy trial. Abstract presented at FIGO 2009 - 19th World Congress of Gynecology & Obstetrics. Cape Town, South Africa, 4-9 October, 2009.

Publications automatically indexed to this study:


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00122681     History of Changes
Other Study ID Numbers: 580299/008
Study First Received: July 20, 2005
Results First Received: November 30, 2009
Last Updated: July 11, 2013
Health Authority: United States: Food and Drug Administration