Safety of and Immune Response to a Novel Human Papillomavirus Vaccine in HIV Infected Children

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00339040
First received: June 19, 2006
Last updated: February 24, 2014
Last verified: February 2014
Results First Received: September 7, 2011  
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: HIV Infections
Sexually Transmitted Diseases
Interventions: Biological: Quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle (VLP) or Quadrivalent human papillomavirus vaccine (QHPV)
Other: Placebo/QHPV

  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
Between October 11, 2006 and November 22, 2006 130 participants were enrolled at 34 clinical sites from US & Puerto Rico.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were stratified by CD4% criteria. Four participants were randomized but did not receive the study treatment. The study analyses were based on 126 participants who received the study treatment.

Reporting Groups
  Description
Arm A QHPV Participants received three doses of the quadrivalent human papillomavirus vaccine (QHPV) (Types 6, 11, 16, 18) at week 0, 8, and 24 and an additional dose at week 96.
Arm B Placebo/QHPV Participants received three doses of the placebo at week 0, 8, and 24 and additional dose of the quadrivalent human papillomavirus vaccine (QHPV) (Types 6, 11, 16, 18) at week 96, 104 and 120.

Participant Flow for 2 periods

Period 1:   Stage I
    Arm A QHPV     Arm B Placebo/QHPV  
STARTED     96     30  
Vaccination 1 at Week 0     96     30  
Vaccination 2 at Week 8     95     30  
Vaccination 3 at Week 24     94     30  
COMPLETED     94     29  
NOT COMPLETED     2     1  
Not able to attend clinic                 1                 0  
Protocol Violation                 1                 1  

Period 2:   Stage II
    Arm A QHPV     Arm B Placebo/QHPV  
STARTED     94     29  
Vaccination 4 at Week 96     84     29  
Vaccination 5 at Week 104     0     28  
Vaccination 6 at Week 120     0     27  
COMPLETED     84     27  
NOT COMPLETED     10     2  
Lost to Follow-up                 3                 0  
Withdrawal by Subject                 1                 2  
Protocol Violation                 3                 0  
Not able to attend clinic                 1                 0  
Site closing                 2                 0  



  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
Arm A QHPV Participants received three doses of the quadrivalent human papillomavirus vaccine (QHPV) (Types 6, 11, 16, 18) at week 0, 8, and 24 and an additional dose at week 96.
Arm B Placebo/QHPV Participants received three doses of the placebo at week 0, 8, and 24 and additional dose of the quadrivalent human papillomavirus vaccine (QHPV) (Types 6, 11, 16, 18) at week 96, 104 and 120.
Total Total of all reporting groups

Baseline Measures
    Arm A QHPV     Arm B Placebo/QHPV     Total  
Number of Participants  
[units: participants]
  96     30     126  
Age  
[units: years]
Mean ± Standard Deviation
  10.0  ± 1.4     9.9  ± 1.3     9.9  ± 1.4  
Gender  
[units: participants]
     
Female     53     18     71  
Male     43     12     55  
Race/Ethnicity, Customized  
[units: participants]
     
White, non-Hispanic     4     2     6  
Black, non-Hispanic     54     11     65  
Hispanic     37     14     51  
Others     1     3     4  
Stratification groups [1]
[units: participants]
     
Stratum A     31     10     41  
Stratum B     32     11     43  
Stratum C     33     9     42  
CD4 count  
[units: cells/µL]
Mean ± Standard Deviation
  868  ± 367     1013  ± 455     903  ± 393  
CD4%  
[units: percentage of total lymphocytes]
Mean ± Standard Deviation
  33.9  ± 7.9     35.8  ± 8.6     34.3  ± 8.1  
Log10(RNA)  
[units: Log10(copies/mL)]
Mean ± Standard Deviation
  2.7  ± 0.9     2.6  ± 0.8     2.7  ± 0.9  
RNA group  
[units: participants]
     
≤400 copies/mL     65     22     87  
401 to ≤5000 copies/mL     16     5     21  
>5000 copies/mL     15     3     18  
[1]

STRATIFICATION: Participant were stratified by CD4% criteria into three strata:

  • Stratum A: CD4% Nadir < 15 and CD4% ≥ 15 at screening
  • Stratum B: CD4% Nadir ≥ 15 and < 25 and CD4% ≥ 15 at screening
  • Stratum C: CD4% Nadir ≥ 25 and CD4% ≥ 25 at screening



  Outcome Measures
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1.  Primary:   Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs)   [ Time Frame: Within 14 days of first three doses of vaccination ]

2.  Primary:   Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) Attributed to Study Treatment   [ Time Frame: Within 14 days of first three doses of vaccination ]

3.  Primary:   Percent of Participants With Human Papillomavirus (HPV) Type-Specific Seroconversion   [ Time Frame: At week 28 after beginning the vaccination series ]

4.  Primary:   Serum Anti-HPV Antibody Titers (cLIA)   [ Time Frame: Arm A week 0, 28, 72, 96, 97, 100; Arm B week 0, 28, 72, 96, 97, 100, 124. ]

5.  Secondary:   CD4 Count Over Time   [ Time Frame: Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124. ]

6.  Secondary:   CD4 Percent Over Time   [ Time Frame: Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124. ]

7.  Secondary:   HIV-1 Viral Load (Ribonucleic Acid [RNA] Copies/ml) Over Time   [ Time Frame: Arm A week 0, 8, 12, 24, 28, 72, 96, 100 and 108; Arm B week 0, 8, 12, 24, 28, 72, 96, 100, 104, 108, 120, and 124. ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame Adverse events were reported from the time when participants started to receive study treatment until study completion and before August 10, 2009 (primary completion date).
Additional Description Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and >=grade 3 AEs defined by the "DAIDS Table for Grading the Severity of Adult and Pediatric AEs", V1.0, 12/2004.

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

Reporting Groups
  Description
Arm A QHPV Participants received three doses of the quadrivalent human papillomavirus vaccine (QHPV) (Types 6, 11, 16, 18) at week 0, 8, and 24 and an additional dose at week 96.
Arm B Placebo/QHPV Participants received three doses of the placebo at week 0, 8, and 24 and additional dose of the quadrivalent human papillomavirus vaccine (QHPV) (Types 6, 11, 16, 18) at week 96, 104 and 120.

Other Adverse Events
    Arm A QHPV     Arm B Placebo/QHPV  
Total, other (not including serious) adverse events      
# participants affected / at risk     93/96     30/30  
Ear and labyrinth disorders      
Ear pain † 1    
# participants affected / at risk     5/96 (5.21%)     3/30 (10.00%)  
Eye disorders      
Conjunctivitis † 1    
# participants affected / at risk     5/96 (5.21%)     0/30 (0.00%)  
Gastrointestinal disorders      
Abdominal pain † 1    
# participants affected / at risk     7/96 (7.29%)     0/30 (0.00%)  
Abdominal pain upper † 1    
# participants affected / at risk     6/96 (6.25%)     0/30 (0.00%)  
Diarrhoea † 1    
# participants affected / at risk     7/96 (7.29%)     2/30 (6.67%)  
Vomiting † 1    
# participants affected / at risk     9/96 (9.38%)     4/30 (13.33%)  
General disorders      
Chest pain † 1    
# participants affected / at risk     5/96 (5.21%)     0/30 (0.00%)  
Gait disturbance † 1    
# participants affected / at risk     0/96 (0.00%)     2/30 (6.67%)  
Injection site pain † 1    
# participants affected / at risk     13/96 (13.54%)     2/30 (6.67%)  
Pyrexia † 1    
# participants affected / at risk     14/96 (14.58%)     10/30 (33.33%)  
Infections and infestations      
Acute sinusitis † 1    
# participants affected / at risk     4/96 (4.17%)     5/30 (16.67%)  
Gastroenteritis † 1    
# participants affected / at risk     7/96 (7.29%)     0/30 (0.00%)  
Otitis media acute † 1    
# participants affected / at risk     4/96 (4.17%)     3/30 (10.00%)  
Pharyngitis † 1    
# participants affected / at risk     5/96 (5.21%)     3/30 (10.00%)  
Pharyngitis streptococcal † 1    
# participants affected / at risk     3/96 (3.13%)     3/30 (10.00%)  
Pneumonia † 1    
# participants affected / at risk     2/96 (2.08%)     2/30 (6.67%)  
Purulent discharge † 1    
# participants affected / at risk     0/96 (0.00%)     2/30 (6.67%)  
Investigations      
Alanine aminotransferase increased † 1    
# participants affected / at risk     20/96 (20.83%)     6/30 (20.00%)  
Aspartate aminotransferase increased † 1    
# participants affected / at risk     15/96 (15.63%)     10/30 (33.33%)  
Blood albumin abnormal † 1    
# participants affected / at risk     3/96 (3.13%)     2/30 (6.67%)  
Blood alkaline phosphatase increased † 1    
# participants affected / at risk     14/96 (14.58%)     1/30 (3.33%)  
Blood bicarbonate abnormal † 1    
# participants affected / at risk     21/96 (21.88%)     5/30 (16.67%)  
Blood bilirubin increased † 1    
# participants affected / at risk     11/96 (11.46%)     6/30 (20.00%)  
Blood cholesterol increased † 1    
# participants affected / at risk     17/96 (17.71%)     4/30 (13.33%)  
Blood creatinine increased † 1    
# participants affected / at risk     5/96 (5.21%)     3/30 (10.00%)  
Blood glucose decreased † 1    
# participants affected / at risk     37/96 (38.54%)     10/30 (33.33%)  
Blood glucose increased † 1    
# participants affected / at risk     12/96 (12.50%)     7/30 (23.33%)  
Blood phosphorus decreased † 1    
# participants affected / at risk     7/96 (7.29%)     1/30 (3.33%)  
Blood potassium decreased † 1    
# participants affected / at risk     12/96 (12.50%)     3/30 (10.00%)  
Blood sodium decreased † 1    
# participants affected / at risk     28/96 (29.17%)     11/30 (36.67%)  
Blood triglycerides increased † 1    
# participants affected / at risk     7/96 (7.29%)     0/30 (0.00%)  
Haemoglobin decreased † 1    
# participants affected / at risk     5/96 (5.21%)     1/30 (3.33%)  
Neutrophil count decreased † 1    
# participants affected / at risk     36/96 (37.50%)     10/30 (33.33%)  
Platelet count decreased † 1    
# participants affected / at risk     2/96 (2.08%)     2/30 (6.67%)  
Musculoskeletal and connective tissue disorders      
Pain in extremity † 1    
# participants affected / at risk     3/96 (3.13%)     2/30 (6.67%)  
Nervous system disorders      
Headache † 1    
# participants affected / at risk     6/96 (6.25%)     2/30 (6.67%)  
Respiratory, thoracic and mediastinal disorders      
Asthma † 1    
# participants affected / at risk     3/96 (3.13%)     4/30 (13.33%)  
Bronchial hyperreactivity † 1    
# participants affected / at risk     1/96 (1.04%)     2/30 (6.67%)  
Cough † 1    
# participants affected / at risk     13/96 (13.54%)     9/30 (30.00%)  
Nasal congestion † 1    
# participants affected / at risk     10/96 (10.42%)     6/30 (20.00%)  
Oropharyngeal pain † 1    
# participants affected / at risk     11/96 (11.46%)     6/30 (20.00%)  
Rhonchi † 1    
# participants affected / at risk     0/96 (0.00%)     2/30 (6.67%)  
Wheezing † 1    
# participants affected / at risk     5/96 (5.21%)     5/30 (16.67%)  
Skin and subcutaneous tissue disorders      
Rash † 1    
# participants affected / at risk     5/96 (5.21%)     2/30 (6.67%)  
Skin lesion † 1    
# participants affected / at risk     0/96 (0.00%)     2/30 (6.67%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 14.0



  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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