Comparison of Three Hepatitis B Vaccination Regimens in HIV-Positive Youth

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00106964
First received: April 1, 2005
Last updated: October 8, 2013
Last verified: August 2013
Results First Received: October 26, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Conditions: HIV Infection
Hepatitis B
Interventions: Biological: Engerix-B 20 mcg
Biological: Engerix-B 40 mcg
Biological: Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This is a multi-site study. Accrual was open between April 2006 and January 2008. Participants were enrolled in the United States, South Africa, Brazil, and the Bahamas.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects were randomized into one of three arms using blocks of six and stratified by absolute CD4 count (less than 500 and 500 cells/mL or greater) and previous hepatitis B virus (HBV) vaccination (0,1). The randomization was restricted so that the percentage of subjects with CD4 count < = 200 cells/mL would not exceed 15% of subjects on any arm.

Reporting Groups
  Description
1: Engerix 20 Mcg Standard dose (20 mcg) of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
2: Engerix 40 Mcg 40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
3: Twinrix 20 Mcg 20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.

Participant Flow:   Overall Study
    1: Engerix 20 Mcg     2: Engerix 40 Mcg     3: Twinrix 20 Mcg  
STARTED     118     126     127  
COMPLETED     105 [1]   111 [2]   120 [3]
NOT COMPLETED     13     15     7  
Lost to Follow-up                 8                 6                 2  
Pregnancy                 2                 3                 2  
Death                 1                 1                 0  
Incarceration                 0                 1                 0  
Site Funding Terminated                 0                 1                 1  
Failure to adhere                 2                 0                 0  
Did not meet eligibility criteria                 0                 2                 2  
Required disallowed medication                 0                 1                 0  
[1] The number of those those who completed the vaccine series was 105.
[2] The number of those who completed the vaccine series was 111.
[3] The number of those who completed the vaccine series was 120.



  Baseline Characteristics
  Hide Baseline Characteristics

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
1: Engerix 20 Mcg Standard dose (20 mcg) of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
2: Engerix 40 Mcg 40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
3: Twinrix 20 Mcg 20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
Total Total of all reporting groups

Baseline Measures
    1: Engerix 20 Mcg     2: Engerix 40 Mcg     3: Twinrix 20 Mcg     Total  
Number of Participants  
[units: participants]
  118     126     127     371  
Age  
[units: years]
Mean ± Standard Deviation
  20.56  ± 3.42     20.96  ± 3.25     20.20  ± 3.50     20.57  ± 3.40  
Age, Customized  
[units: participants]
       
12-13 years     8     3     8     19  
14-15 years     5     11     10     26  
16-19 years     25     18     20     63  
>20 years     80     94     89     263  
Gender  
[units: participants]
       
Female     73     74     80     227  
Male     45     52     47     144  
Region of Enrollment  
[units: participants]
       
United States     52     54     49     155  
South Africa     4     6     13     23  
Brazil     52     58     58     168  
Bahamas     10     8     7     25  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Sero-response to Hepatitis B Surface Antigen   [ Time Frame: Week 28 ]

2.  Secondary:   Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - POSSIBLY OR PROBABLY RELATED   [ Time Frame: Baseline through Week 72 ]

3.  Secondary:   Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - DEFINITELY RELATED   [ Time Frame: Baseline through Week 72 ]
  Hide Outcome Measure 3

Measure Type Secondary
Measure Title Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - DEFINITELY RELATED
Measure Description The number of AEs was described by study arm. The proportion of subjects with clinical AEs in Arms 1 and each of the two alternative strategy arms (Arm 2 and Arm 3)were compared to assess whether or not there is a difference in subjects with any grade toxicity.
Time Frame Baseline through Week 72  
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.
All enrolled participants were included in this analysis of AEs that were definitely related to study drug. There were no AEs above Grade 2 considered to be definitely related to study drug.

Reporting Groups
  Description
1: Engerix 20 Mcg Standard dose (20 mcg) of Hepatitis B vaccine. Number of participants with a Grade 1 event that was definitely related to study drug as determined by the Site Investigator.
2: Engerix 40 Mcg Engerix 40 mcg vaccine. Number of participants with a Grade 1 event that was definitely related to study drug as determined by the Site Investigator.
3: Twinrix 20 Mcg Twinrix 20 mcg vaccine. Number of participants with a Grade 1 event that was definitely related to study drug as determined by the Site Investigator.

Measured Values
    1: Engerix 20 Mcg     2: Engerix 40 Mcg     3: Twinrix 20 Mcg  
Number of Participants Analyzed  
[units: participants]
  118     126     127  
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - DEFINITELY RELATED  
[units: event]
     
Injection Site Pain, Grade 1     1     0     1  
Myalgia, Grade 2     1     0     1  

No statistical analysis provided for Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - DEFINITELY RELATED



4.  Secondary:   Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth – ABNORMAL LABORATORY VALUES GRADE 2 OR ABOVE BY INTERVENTION ARM ON STUDY   [ Time Frame: Baseline through Week 72 ]

5.  Secondary:   Response Rates in HIV+ Youth Within Each Study Arm by Study Duration   [ Time Frame: Entry through Week 72 ]

6.  Secondary:   Sero-Response to Hepatitis B Surface Antigen; Predictor: STUDY ARM   [ Time Frame: Week 28 ]


  Serious Adverse Events


  Other Adverse Events


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


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
No text entered.  


Results Point of Contact:  
Name/Title: James Korelitz
Organization: Westat
phone: 301-251-1500
e-mail: jameskorelitz@westat.com


Publications of Results:

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00106964     History of Changes
Other Study ID Numbers: ATN 024
Study First Received: April 1, 2005
Results First Received: October 26, 2012
Last Updated: October 8, 2013
Health Authority: United States: Federal Government