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
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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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
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. ]

2.  Primary:   Number of Subjects Reporting Severe (Grade 3) Solicited Local Symptoms.   [ Time Frame: Within 7 days (Days 0-6) after vaccination. ]

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. ]

4.  Primary:   Number of Subjects Reporting Any and Related Unsolicited Symptoms.   [ Time Frame: Within 30 days (Days 0-29) after vaccination. ]

5.  Primary:   Number of Subjects Reporting Severe (Grade 3) Unsolicited Symptoms.   [ Time Frame: Within 30 days (Days 0-29) after vaccination. ]

6.  Primary:   Number of Subjects With Medically Significant Conditions.   [ Time Frame: Up to Month 7. ]

7.  Primary:   Number of Subjects Reporting Serious Adverse Events (SAEs).   [ Time Frame: Up to Month 7. ]

8.  Primary:   Number of Subjects With Medically Significant Conditions.   [ Time Frame: Up to Month 12. ]

9.  Primary:   Number of Subjects Reporting Serious Adverse Events (SAEs).   [ Time Frame: Up to Month 12. ]

10.  Primary:   Number of Subjects With Pregnancies and Their Outcome.   [ Time Frame: Up to Month 12. ]

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 ]

12.  Primary:   Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.   [ Time Frame: At month 10 and month12. ]

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. ]

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. ]

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. ]

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 ]

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. ]

18.  Primary:   HIV Viral Load at Each Time Point in All HIV+ Subjects.   [ Time Frame: At Month 10 and Month 12 ]

19.  Primary:   Number of Seroconverted Subjects for HPV-16 and HPV-18 Antibodies.   [ Time Frame: At Months 2 and 7 ]

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

21.  Primary:   Concentrations for HPV-16 and HPV-18 Antibodies.   [ Time Frame: At Months 0, 2 and 7. ]

22.  Primary:   Concentrations for HPV-16 and HPV-18 Antibodies.   [ Time Frame: At Month 12. ]

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. ]

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 ]

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 ]

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 ]

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 ]

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 ]

29.  Primary:   Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.   [ Time Frame: At Month 10 and Month 12 ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame Serious adverse events were assessed up to Month 12. Systematically and non-systematically assessed frequent adverse events were assessed within the 7 day (Days 0-6) and 30 day (Days 0-29) post-vaccination period respectively.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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.

Other Adverse Events
    HIV+/Cervarix Group     HIV+/Aluminium Hydroxide Group     HIV-/Cervarix Group  
Total, other (not including serious) adverse events        
# participants affected / at risk     52/61     27/59     28/30  
Gastrointestinal disorders        
Diarrhoea *      
# participants affected / at risk     4/61 (6.56%)     6/59 (10.17%)     1/30 (3.33%)  
Dyspepsia *      
# participants affected / at risk     1/61 (1.64%)     1/59 (1.69%)     2/30 (6.67%)  
General disorders        
Injection site erythema *      
# participants affected / at risk     7/61 (11.48%)     1/59 (1.69%)     4/30 (13.33%)  
Injection site induration *      
# participants affected / at risk     4/61 (6.56%)     0/59 (0.00%)     4/30 (13.33%)  
Injection site pruritus *      
# participants affected / at risk     3/61 (4.92%)     0/59 (0.00%)     2/30 (6.67%)  
Pain      
# participants affected / at risk     52/61 (85.25%)     27/59 (45.76%)     28/30 (93.33%)  
Swelling      
# participants affected / at risk     19/61 (31.15%)     2/59 (3.39%)     12/30 (40.00%)  
Arthralgia      
# participants affected / at risk     4/61 (6.56%)     4/59 (6.78%)     2/30 (6.67%)  
Fatigue      
# participants affected / at risk     18/61 (29.51%)     16/59 (27.12%)     8/30 (26.67%)  
Fever      
# participants affected / at risk     2/61 (3.28%)     3/59 (5.08%)     2/30 (6.67%)  
Gastrointestinal      
# participants affected / at risk     15/61 (24.59%)     11/59 (18.64%)     13/30 (43.33%)  
Headache      
# participants affected / at risk     23/61 (37.70%)     26/59 (44.07%)     16/30 (53.33%)  
Myalgia      
# participants affected / at risk     3/61 (4.92%)     3/59 (5.08%)     7/30 (23.33%)  
Infections and infestations        
Upper respiratory tract infection *      
# participants affected / at risk     10/61 (16.39%)     10/59 (16.95%)     7/30 (23.33%)  
Nasopharyngitis *      
# participants affected / at risk     3/61 (4.92%)     6/59 (10.17%)     3/30 (10.00%)  
Vulvovaginal candidiasis *      
# participants affected / at risk     5/61 (8.20%)     4/59 (6.78%)     0/30 (0.00%)  
Urinary tract infection *      
# participants affected / at risk     1/61 (1.64%)     2/59 (3.39%)     2/30 (6.67%)  
Musculoskeletal and connective tissue disorders        
Back pain *      
# participants affected / at risk     5/61 (8.20%)     4/59 (6.78%)     3/30 (10.00%)  
Nervous system disorders        
Headache *      
# participants affected / at risk     12/61 (19.67%)     14/59 (23.73%)     4/30 (13.33%)  
Dizziness *      
# participants affected / at risk     4/61 (6.56%)     4/59 (6.78%)     2/30 (6.67%)  
Respiratory, thoracic and mediastinal disorders        
Cough *      
# participants affected / at risk     8/61 (13.11%)     5/59 (8.47%)     4/30 (13.33%)  
Epistaxis *      
# participants affected / at risk     0/61 (0.00%)     3/59 (5.08%)     1/30 (3.33%)  
Skin and subcutaneous tissue disorders        
Rash *      
# participants affected / at risk     2/61 (3.28%)     0/59 (0.00%)     2/30 (6.67%)  
Events were collected by systematic assessment
* Events were collected by non-systematic assessment



  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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