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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: August 29, 2016
Last verified: August 2016
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
Condition: Infections, Papillomavirus
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 
Overall Participants Analyzed 
[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
  Show All Outcome Measures

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. ]
  Hide Outcome Measure 12

Measure Type Primary
Measure Title Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.
Measure Description Laboratory parameters assessed were alanine aminotransferase (ALAT), creatinine (CREA), white blood cells (WBC), neutrophils (NEU), lymphocytes (LYM), monocytes (MON), eosinophils (EOS), basophils (BAS), red blood cells (RBC), haemoglobin (Hgb), haematocrit (Hct) and platelets (PLA). For each parameter and by pre-vaccination status, it was assessed whether the post-vaccination values of the parameter were above, below or in the normal range (missing values are also indicated). Parameters presented in this table are ALAT, BAS, CREA, EOS, Hct, Hgb, LYM and MON.
Time Frame At month 10 and month12.  
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 Total Vaccinated cohort included all vaccinated subjects for whom data were available.

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 
Participants Analyzed 
[Units: Participants]
 60   57   29 
Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed. 
[Units: Subjects]
     
ALAT [pre-vacc Normal; post-vacc Normal] Month 10   44   40   20 
ALAT [pre-vacc Normal; post-vacc Below] Month 10   0   0   0 
ALAT [pre-vacc Normal; post-vacc Above] Month 10   1   4   1 
ALAT [pre-vacc Normal; post-vacc Missing] Month 10   0   0   0 
ALAT [pre-vacc Normal; post-vacc Normal] Month 12   38   39   20 
ALAT [pre-vacc Normal; post-vacc Below] Month 12   0   0   0 
ALAT [pre-vacc Normal; post-vacc Above] Month 12   6   6   1 
ALAT [pre-vacc Normal; post-vacc Missing] Month 12   0   0   0 
ALAT [pre-vacc Low; post-vacc Normal] Month 10   0   0   0 
ALAT [pre-vacc Low; post-vacc Below] Month 10   1   0   0 
ALAT [pre-vacc Low; post-vacc Above] Month 10   0   0   0 
ALAT [pre-vacc Low; post-vacc Missing] Month 10   0   0   0 
ALAT [pre-vacc Low; post-vacc Normal] Month 12   0   0   0 
ALAT [pre-vacc Low; post-vacc Below] Month 12   1   0   0 
ALAT [pre-vacc Low; post-vacc Above] Month 12   0   0   0 
ALAT [pre-vacc Low; post-vacc Missing] Month 12   0   0   0 
ALAT [pre-vacc High; post-vacc Normal] Month 10   8   4   1 
ALAT [pre-vacc High; post-vacc Below] Month 10   0   0   0 
ALAT [pre-vacc High; post-vacc Above] Month 10   1   2   2 
ALAT [pre-vacc High; post-vacc Missing] Month 10   0   0   0 
ALAT [pre-vacc High; post-vacc Normal] Month 12   8   5   2 
ALAT [pre-vacc High; post-vacc Below] Month 12   0   0   0 
ALAT [pre-vacc High; post-vacc Above] Month 12   1   2   1 
ALAT [pre-vacc High; post-vacc Missing] Month 12   0   0   0 
BAS [pre-vacc Normal; post-vacc Normal] Month 10   55   50   24 
BAS [pre-vacc Normal; post-vacc Below] Month 10   0   0   0 
BAS [pre-vacc Normal; post-vacc Above] Month 10   0   0   0 
BAS [pre-vacc Normal; post-vacc Missing] Month 10   0   0   0 
BAS [pre-vacc Normal; post-vacc Normal] Month 12   54   52   24 
BAS [pre-vacc Normal; post-vacc Below] Month 12   0   0   0 
BAS [pre-vacc Normal; post-vacc Above] Month 12   0   0   0 
BAS [pre-vacc Normal; post-vacc Missing] Month 12   0   0   0 
CREA [pre-vacc Normal; post-vacc Normal] Month 10   20   22   15 
CREA [pre-vacc Normal; post-vacc Below] Month 10   4   11   4 
CREA [pre-vacc Normal; post-vacc Above] Month 10   0   0   0 
CREA [pre-vacc Normal; post-vacc Missing] Month 10   0   0   0 
CREA [pre-vacc Normal; post-vacc Normal] Month 12   18   24   13 
CREA [pre-vacc Normal; post-vacc Below] Month 12   6   10   6 
CREA [pre-vacc Normal; post-vacc Above] Month 12   0   0   0 
CREA [pre-vacc Normal; post-vacc Missing] Month 12   0   0   0 
CREA [pre-vacc Low; post-vacc Normal] Month 10   11   4   2 
CREA [pre-vacc Low; post-vacc Below] Month 10   20   13   3 
CREA [pre-vacc Low ; post-vacc Above] Month 10   0   0   0 
CREA [pre-vacc Low; post-vacc Missing] Month 10   0   0   0 
CREA [pre-vacc Low; post-vacc Normal] Month 12   4   4   3 
CREA [pre-vacc Low; post-vacc Below] Month 12   26   14   2 
CREA [pre-vacc Low; post-vacc Above] Month 12   0   0   0 
CREA [pre-vacc Low; post-vacc Missing] Month 12   0   0   0 
EOS [pre-vacc Normal; post-vacc Normal] Month 10   46   46   22 
EOS [pre-vacc Normal; post-vacc Below] Month 10   0   0   0 
EOS [pre-vacc Normal ; post-vacc Above] Month 10   3   2   2 
EOS [pre-vacc Normal; post-vacc Missing] Month 10   0   0   0 
EOS [pre-vacc Normal; post-vacc Normal] Month 12   46   49   24 
EOS [pre-vacc Normal; post-vacc Below] Month 12   0   0   0 
EOS [pre-vacc Normal; post-vacc Above] Month 12   2   1   0 
EOS [pre-vacc Normal; post-vacc Missing] Month 12   0   0   0 
EOS [pre-vacc High; post-vacc Normal] Month 10   3   2   0 
EOS [pre-vacc High; post-vacc Below] Month 10   0   0   0 
EOS [pre-vacc High; post-vacc Above] Month 10   3   0   0 
EOS [pre-vacc High; post-vacc Missing] Month 10   0   0   0 
EOS [pre-vacc High; post-vacc Normal] Month 12   4   2   0 
EOS [pre-vacc High; post-vacc Below] Month 12   0   0   0 
EOS [pre-vacc High; post-vacc Above] Month 12   2   0   0 
EOS [pre-vacc High; post-vacc Missing] Month 12   0   0   0 
Hct [pre-vacc Normal; post-vacc Normal] Month 10   35   31   20 
Hct [pre-vacc Normal; post-vacc Below] Month 10   6   7   2 
Hct [pre-vacc Normal ; post-vacc Above] Month 10   0   0   0 
Hct [pre-vacc Normal; post-vacc Missing] Month 10   0   0   0 
Hct [pre-vacc Normal; post-vacc Normal] Month 12   32   32   22 
Hct [pre-vacc Normal; post-vacc Below] Month 12   9   8   0 
Hct [pre-vacc Normal; post-vacc Above] Month 12   0   0   0 
Hct [pre-vacc Normal; post-vacc Missing] Month 12   0   0   0 
Hct [pre-vacc Low; post-vacc Normal] Month 10   6   4   1 
Hct [pre-vacc Low; post-vacc Below] Month 10   8   7   1 
Hct [pre-vacc Low ; post-vacc Above] Month 10   0   0   0 
Hct [pre-vacc Low; post-vacc Missing] Month 10   0   0   0 
Hct [pre-vacc Low; post-vacc Normal] Month 12   4   4   1 
Hct [pre-vacc Low; post-vacc Below] Month 12   9   7   1 
Hct [pre-vacc Low; post-vacc Above] Month 12   0   0   0 
Hct [pre-vacc Low; post-vacc Missing] Month 12   0   0   0 
Hct [pre-vacc High; post-vacc Normal] Month 10   0   0   0 
Hct [pre-vacc High; post-vacc Below] Month 10   0   1   0 
Hct [pre-vacc High; post-vacc Above] Month 10   0   0   0 
Hct [pre-vacc High; post-vacc Missing] Month 10   0   0   0 
Hct [pre-vacc High; post-vacc Normal] Month 12   0   1   0 
Hct [pre-vacc High; post-vacc Below] Month 12   0   0   0 
Hct [pre-vacc High; post-vacc Above] Month 12   0   0   0 
Hct [pre-vacc High; post-vacc Missing] Month 12   0   0   0 
Hgb [pre-vacc Normal; post-vacc Normal] Month 10   44   38   21 
Hgb [pre-vacc Normal; post-vacc Below] Month 10   2   5   0 
Hgb [pre-vacc Normal ; post-vacc Above] Month 10   0   0   0 
Hgb [pre-vacc Normal; post-vacc Missing] Month 10   0   0   0 
Hgb [pre-vacc Normal; post-vacc Normal] Month 12   43   42   21 
Hgb [pre-vacc Normal; post-vacc Below] Month 12   2   3   0 
Hgb [pre-vacc Normal; post-vacc Above] Month 12   0   0   0 
Hgb [pre-vacc Normal; post-vacc Missing] Month 12   0   0   0 
Hgb [pre-vacc Low; post-vacc Normal] Month 10   2   5   1 
Hgb [pre-vacc Low; post-vacc Below] Month 10   7   2   2 
Hgb [pre-vacc Low ; post-vacc Above] Month 10   0   0   0 
Hgb [pre-vacc Low; post-vacc Missing] Month 10   0   0   0 
Hgb [pre-vacc Low; post-vacc Normal] Month 12   4   4   3 
Hgb [pre-vacc Low; post-vacc Below] Month 12   5   3   0 
Hgb [pre-vacc Low; post-vacc Above] Month 12   0   0   0 
Hgb [pre-vacc Low; post-vacc Missing] Month 12   0   0   0 
LYM [pre-vacc Normal; post-vacc Normal] Month 10   46   48   21 
LYM [pre-vacc Normal; post-vacc Below] Month 10   3   1   0 
LYM [pre-vacc Normal; post-vacc Above] Month 10   0   0   1 
LYM [pre-vacc Normal; post-vacc Missing] Month 10   0   0   0 
LYM [pre-vacc Normal; post-vacc Normal] Month 12   45   48   21 
LYM [pre-vacc Normal; post-vacc Below] Month 12   3   2   1 
LYM [pre-vacc Normal; post-vacc Above] Month 12   0   1   0 
LYM [pre-vacc Normal; post-vacc Missing] Month 12   0   0   0 
LYM [pre-vacc Low; post-vacc Normal] Month 10   4   1   1 
LYM [pre-vacc Low; post-vacc Below] Month 10   1   0   0 
LYM [pre-vacc Low; post-vacc Above] Month 10   0   0   0 
LYM [pre-vacc Low; post-vacc Missing] Month 10   0   0   0 
LYM [pre-vacc Low; post-vacc Normal] Month 12   3   1   1 
LYM [pre-vacc Low; post-vacc Below] Month 12   2   0   0 
LYM [pre-vacc Low; post-vacc Above] Month 12   0   0   0 
LYM [pre-vacc Low; post-vacc Missing] Month 12   0   0   0 
LYM [pre-vacc High; post-vacc Normal] Month 10   1   0   1 
LYM [pre-vacc High; post-vacc Below] Month 10   0   0   0 
LYM [pre-vacc High; post-vacc Above] Month 10   0   0   0 
LYM [pre-vacc High; post-vacc Missing] Month 10   0   0   0 
LYM [pre-vacc High; post-vacc Normal] Month 12   1   0   1 
LYM [pre-vacc High; post-vacc Below] Month 12   0   0   0 
LYM [pre-vacc High; post-vacc Above] Month 12   0   0   0 
LYM [pre-vacc High; post-vacc Missing] Month 12   0   0   0 
MON [pre-vacc Normal; post-vacc Normal] Month 10   50   48   24 
MON [pre-vacc Normal; post-vacc Below] Month 10   2   1   0 
MON [pre-vacc Normal; post-vacc Above] Month 10   0   0   0 
MON [pre-vacc Normal; post-vacc Missing] Month 10   0   0   0 
MON [pre-vacc Normal; post-vacc Normal] Month 12   50   45   24 
MON [pre-vacc Normal; post-vacc Below] Month 12   1   5   0 
MON [pre-vacc Normal; post-vacc Above] Month 12   0   1   0 
MON [pre-vacc Normal; post-vacc Missing] Month 12   0   0   0 
MON [pre-vacc Low; post-vacc Normal] Month 10   2   1   0 
MON [pre-vacc Low; post-vacc Below] Month 10   1   0   0 
MON [pre-vacc Low; post-vacc Above] Month 10   0   0   0 
MON [pre-vacc Low; post-vacc Missing] Month 10   0   0   0 
MON [pre-vacc Low; post-vacc Normal] Month 12   2   1   0 
MON [pre-vacc Low; post-vacc Below] Month 12   1   0   0 
MON [pre-vacc Low; post-vacc Above] Month 12   0   0   0 
MON [pre-vacc Low; post-vacc Missing] Month 12   0   0   0 

No statistical analysis provided for Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.



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


  Limitations and Caveats
  Hide 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
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  More Information