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

This study has been completed.
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00339040
First received: June 19, 2006
Last updated: December 30, 2014
Last verified: December 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 
Overall Participants Analyzed 
[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 
[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
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 


  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 ]
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Measure Type Primary
Measure Title Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs)
Measure Description Adverse events were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (December 2004). The grades used are: Grade 1="Mild", Grade 2="Moderate", Grade 3="Severe", Grade 4="Potentially Life-Threatening". All grade 3 and higher signs, symptoms, and laboratory toxicities were included.
Time Frame Within 14 days of first three doses of vaccination  
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 were included in the safety analysis.

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 
Participants Analyzed 
[Units: Participants]
 96   30 
Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs) 
[Units: Percent of participants]
Number (95% Confidence Interval)
 7.3 
 (3.0 to 14.5) 
 6.7 
 (0.8 to 22.1) 


Statistical Analysis 1 for Percent of Participants Developing Grade 3 or 4 Adverse Events (AEs)
Groups [1] All groups
Method [2] Fisher Exact
P Value [3] 1.00
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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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


  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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  More Information