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. ]
  Hide Outcome Measure 6

Measure Type Secondary
Measure Title CD4 Percent Over Time
Measure Description No text entered.
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.  
Safety Issue Yes  

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.
Any participant who received at least one study vaccine/placebo and with non-missing CD4%.

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.

Measured Values
    Arm A QHPV     Arm B Placebo/QHPV  
Number of Participants Analyzed  
[units: participants]
  96     30  
CD4 Percent Over Time  
[units: percentage of total lymphocytes]
Mean ( 95% Confidence Interval )
   
CD4 percent at study entry (n=96, 30)     34  
  ( 32 to 35 )  
  36  
  ( 33 to 39 )  
CD4 percent at week 8 (n=93, 30)     34  
  ( 32 to 35 )  
  36  
  ( 33 to 39 )  
CD4 percent at week 12 (n=93, 30)     35  
  ( 33 to 37 )  
  37  
  ( 33 to 41 )  
CD4 percent at week 24 (n=94, 30)     34  
  ( 33 to 36 )  
  35  
  ( 31 to 39 )  
CD4 percent at week 28 (n=95, 30)     34  
  ( 33 to 36 )  
  34  
  ( 31 to 38 )  
CD4 percent at week 72 (n=88, 30)     33  
  ( 32 to 35 )  
  34  
  ( 30 to 38 )  
CD4 percent at week 96 (n=88, 30)     33  
  ( 32 to 35 )  
  34  
  ( 30 to 38 )  
CD4 percent at week 100 (n=85, 29)     35  
  ( 33 to 37 )  
  35  
  ( 32 to 39 )  
CD4 percent at week 104 (n=0, 27)     NA  
  ( NA to NA ) [1]
  36  
  ( 32 to 40 )  
CD4 percent at week 108 (n=82, 28)     35  
  ( 33 to 37 )  
  34  
  ( 30 to 38 )  
CD4 percent at week 120 (n=0, 28)     NA  
  ( NA to NA ) [2]
  37  
  ( 32 to 42 )  
CD4 percent at week 124 (n=0, 27)     NA  
  ( NA to NA ) [3]
  35  
  ( 31 to 39 )  
[1] Week 104 is not a designated time point for Arm A.
[2] Week 120 is not a designated time point for Arm A.
[3] Week 124 is not a designated time point for Arm A.

No statistical analysis provided for CD4 Percent Over Time



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


  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
No text entered.


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