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Safety and Immunogenicity of GlaxoSmithKline Biologicals' HPV Vaccine 580299 (Cervarix TM) in HIV Infected Females

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00586339
First received: December 21, 2007
Last updated: July 19, 2012
Last verified: July 2012
History of Changes
Results First Received: February 16, 2012  
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: HPV-16/18 Infections
Cervical Neoplasia
Interventions: Biological: Cervarix TM
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
HIV+ subjects were randomised to receive either Cervarix or Aluminium Hydroxide vaccines; HIV- subjects were not randomised and all received Cervarix vaccine.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Enrolment was staggered as follows: 1) Enrolment of Human immunodeficiency virus positive (HIV+) subjects with cluster of differentiation 4 (CD4+) cell count >200 cells per cubic millimeter (cells/mm^3) and HIV negative (HIV-) subjects (up to 30 subjects) for blinded safety evaluation; 2) Enrolment of remaining HIV+/HIV- subjects.

Reporting Groups
  Description
HIV+/Cervarix Group Human immunodeficiency virus positive (HIV+) subjects received 3 doses of Cervarix™ vaccine at Day 0, Month 1 and Month 6. Cervarix™ vaccines was administrated by intramuscular injection into the deltoid region of the non-dominant arm according to a 0, 1, 6 month schedule.
HIV+/Aluminium Hydroxide Group Human immunodeficiency virus positive (HIV+) subjects received 3 doses of control Aluminium Hydroxide [Al(OH)3] vaccine at Day 0, Month 1 and Month 6. Aluminium Hydroxide vaccine was administrated by intramuscular injection into the deltoid region of the non-dominant arm according to a 0, 1, 6 month schedule.
HIV-/Cervarix Group Human immunodeficiency virus negative (HIV-) subjects received 3 doses of Cervarix™ vaccine at Day 0, Month 1 and Month 6. Cervarix™ vaccines was administrated by intramuscular injection into the deltoid region of the non-dominant arm according to a 0, 1, 6 month schedule.

Participant Flow:   Overall Study
    HIV+/Cervarix Group     HIV+/Aluminium Hydroxide Group     HIV-/Cervarix Group  
STARTED     61     59     30  
COMPLETED     54     52     24  
NOT COMPLETED     7     7     6  
Lost to Follow-up                 6                 4                 5  
Withdrawal by Subject                 1                 3                 1  



  Baseline Characteristics
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Reporting Groups
  Description
HIV+/Cervarix Group Human immunodeficiency virus positive (HIV+) subjects received 3 doses of Cervarix™ vaccine at Day 0, Month 1 and Month 6. Cervarix™ vaccines was administrated by intramuscular injection into the deltoid region of the non-dominant arm according to a 0, 1, 6 month schedule.
HIV+/Aluminium Hydroxide Group Human immunodeficiency virus positive (HIV+) subjects received 3 doses of control Aluminium Hydroxide [Al(OH)3] vaccine at Day 0, Month 1 and Month 6. Aluminium Hydroxide vaccine was administrated by intramuscular injection into the deltoid region of the non-dominant arm according to a 0, 1, 6 month schedule.
HIV-/Cervarix Group Human immunodeficiency virus negative (HIV-) subjects received 3 doses of Cervarix™ vaccine at Day 0, Month 1 and Month 6. Cervarix™ vaccines was administrated by intramuscular injection into the deltoid region of the non-dominant arm according to a 0, 1, 6 month schedule.
Total Total of all reporting groups

Baseline Measures
    HIV+/Cervarix Group     HIV+/Aluminium Hydroxide Group     HIV-/Cervarix Group     Total  
Number of Participants  
[units: participants]
 		  61     59     30     150  
Age  
[units: Years]
Mean ± Standard Deviation 		  21.6  ± 2.21     22.7  ± 1.70     21.3  ± 1.65     21.9  ± 1.85  
Gender  
[units: Subjects]
 		       
Female     61     59     30     150  
Male     0     0     0     0  



  Outcome Measures
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1.  Primary:   Number of Subjects Reporting Any Solicited Local Symptoms.   [ Time Frame: Within 7 days (Days 0-6) after vaccination. ]
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2.  Primary:   Number of Subjects Reporting Severe (Grade 3) Solicited Local Symptoms.   [ Time Frame: Within 7 days (Days 0-6) after vaccination. ]
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3.  Primary:   Number of Subjects Reporting Any, Severe (Grade 3) and Related Solicited General Symptoms.   [ Time Frame: Within 7 days (Days 0-6) after vaccination. ]
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4.  Primary:   Number of Subjects Reporting Any and Related Unsolicited Symptoms.   [ Time Frame: Within 30 days (Days 0-29) after vaccination. ]
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5.  Primary:   Number of Subjects Reporting Severe (Grade 3) Unsolicited Symptoms.   [ Time Frame: Within 30 days (Days 0-29) after vaccination. ]
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6.  Primary:   Number of Subjects With Medically Significant Conditions.   [ Time Frame: Up to Month 7. ]
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7.  Primary:   Number of Subjects Reporting Serious Adverse Events (SAEs).   [ Time Frame: Up to Month 7. ]
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8.  Primary:   Number of Subjects With Medically Significant Conditions.   [ Time Frame: Up to Month 12. ]
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9.  Primary:   Number of Subjects Reporting Serious Adverse Events (SAEs).   [ Time Frame: Up to Month 12. ]
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10.  Primary:   Number of Subjects With Pregnancies and Their Outcome.   [ Time Frame: Up to Month 12. ]
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11.  Primary:   Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.   [ Time Frame: At Day 7, at Months 1, 2, 4, 6 and 7 ]
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12.  Primary:   Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.   [ Time Frame: At month 10 and month12. ]
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13.  Primary:   Number of Subjects in Each World Health Organisation (WHO) HIV Clinical Stage at Each Time Point by Cluster of Differentiation 4 (CD4+) Cell Count Category at Baseline in All HIV+ Subjects.   [ Time Frame: At Months 1, 2, 4, 6 and 7. ]
  Show Outcome Measure 13

14.  Primary:   Number of Subjects in Each World Health Organisation (WHO) HIV Clinical Stage at Each Time Point by Cluster of Differentiation 4 (CD4+) Cell Count Category at Baseline in All HIV+ Subjects.   [ Time Frame: At Month 10 and Month 12. ]
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15.  Primary:   Number of CD4+ Cells Per Cubic Millimeter at Each Time Point in All HIV+ Subjects.   [ Time Frame: At pre-vaccination and at Months 1, 2, 4, 6 and 7. ]
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16.  Primary:   Number of CD4+ Cells Per Cubic Millimetre at Each Time Point in All HIV+ Subjects.   [ Time Frame: At Month 10 and Month 12 ]
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17.  Primary:   HIV Viral Load at Each Time Point in All HIV+ Subjects.   [ Time Frame: At pre-vaccination and at Months 1, 2, 4, 6 and 7. ]
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18.  Primary:   HIV Viral Load at Each Time Point in All HIV+ Subjects.   [ Time Frame: At Month 10 and Month 12 ]
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19.  Primary:   Number of Seroconverted Subjects for HPV-16 and HPV-18 Antibodies.   [ Time Frame: At Months 2 and 7 ]
  Hide Outcome Measure 19

Measure Type Primary
Measure Title Number of Seroconverted Subjects for HPV-16 and HPV-18 Antibodies.
Measure Description

Seroconversion was defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies (anti-HPV-16 titers ≥ 8 ELISA units per millilitre (EL.U/mL) and anti-HPV-18 titers ≥ 7 EL.U/mL) in the serum of subjects seronegative before vaccination.

A seronegative subject was a subject whose antibody titres are below the cut-off value.

Due to the high proportion of initially seropositive subjects in the study population, seroconversion rates were considered for all subjects in the ATP cohort for immunogenicity regardless of baseline serostatus.
Time Frame At Months 2 and 7  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol cohort for immunogenicity included evaluable subjects (i.e. those HPV DNA- subjects during the vaccination phase) for whom data concerning immunogenicity measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post-vaccination.

Reporting Groups
  Description
HIV+/Cervarix Group Human immunodeficiency virus positive (HIV+) subjects received 3 doses of Cervarix™ vaccine at Day 0, Month 1 and Month 6. Cervarix™ vaccines was administrated by intramuscular injection into the deltoid region of the non-dominant arm according to a 0, 1, 6 month schedule.
HIV+/Aluminium Hydroxide Group Human immunodeficiency virus positive (HIV+) subjects received 3 doses of control Aluminium Hydroxide [Al(OH)3] vaccine at Day 0, Month 1 and Month 6. Aluminium Hydroxide vaccine was administrated by intramuscular injection into the deltoid region of the non-dominant arm according to a 0, 1, 6 month schedule.
HIV-/Cervarix Group Human immunodeficiency virus negative (HIV-) subjects received 3 doses of Cervarix™ vaccine at Day 0, Month 1 and Month 6. Cervarix™ vaccines was administrated by intramuscular injection into the deltoid region of the non-dominant arm according to a 0, 1, 6 month schedule.

Measured Values
    HIV+/Cervarix Group     HIV+/Aluminium Hydroxide Group     HIV-/Cervarix Group  
Number of Participants Analyzed  
[units: participants]
 		  43     40     24  
Number of Seroconverted Subjects for HPV-16 and HPV-18 Antibodies.  
[units: Subjects]
 		     
anti-HPV-16 [at Month 2] (N=41;40;24)     41     31     24  
anti-HPV-16 [at Month 7] (N=42;40;24)     42     31     24  
anti-HPV-18 [at Month 2] (N=42;40;24)     42     26     24  
anti-HPV-18 [at Month 7] (N=43;40;24)     43     25     24  

No statistical analysis provided for Number of Seroconverted Subjects for HPV-16 and HPV-18 Antibodies.



20.  Primary:   Number of Seroconverted Subjects for HPV-16 and HPV-18 Antibodies.   [ Time Frame: At Month 12 ]
  Show Outcome Measure 20

21.  Primary:   Concentrations for HPV-16 and HPV-18 Antibodies.   [ Time Frame: At Months 0, 2 and 7. ]
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22.  Primary:   Concentrations for HPV-16 and HPV-18 Antibodies.   [ Time Frame: At Month 12. ]
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23.  Primary:   Cell Mediated Immune Response (CMI) (B-cell and T-cell Responses) Related to HPV-16 and HPV-18 Measured by Intracellullar Cytokine Staining (ICS).   [ Time Frame: At Months 0, 2, 7 and 12. ]
  Show Outcome Measure 23

24.  Primary:   Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.   [ Time Frame: At Day 7, at Months 1, 2, 4, 6 and 7 ]
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25.  Primary:   Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.   [ Time Frame: At Day 7, at Months 1, 2, 4, 6 and 7 ]
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26.  Primary:   Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.   [ Time Frame: At Day 7, at Months 1, 2, 4, 6 and 7 ]
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27.  Primary:   Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.   [ Time Frame: At Day 7, at Months 1, 2, 4, 6 and 7 ]
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28.  Primary:   Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.   [ Time Frame: At Day 7, at Months 1, 2, 4, 6 and 7 ]
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29.  Primary:   Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.   [ Time Frame: At Month 10 and Month 12 ]
  Show Outcome Measure 29


  Serious Adverse Events
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  Other Adverse Events
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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.


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


No publications provided


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00586339     History of Changes
Other Study ID Numbers: 107863
Study First Received: December 21, 2007
Results First Received: February 16, 2012
Last Updated: July 19, 2012
Health Authority: South Africa: Medicines Control Council