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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00106964
Recruitment Status : Completed
First Posted : April 4, 2005
Results First Posted : June 28, 2013
Last Update Posted : March 29, 2017
Sponsor:
Collaborators:
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (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
Enrollment 371
Recruitment Details 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 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.
Arm/Group Title 1: Engerix 20 mcg 2: Engerix 40 mcg 3: Twinrix 20 mcg
Hide Arm/Group Description Standard dose (20 mcg) of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. 40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. 20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
Period Title: Overall Study
Started 118 126 127
Completed 105 [1] 111 [2] 120 [3]
Not Completed 13 15 7
Reason Not Completed
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.
Arm/Group Title 1: Engerix 20 mcg 2: Engerix 40 mcg 3: Twinrix 20 mcg Total
Hide Arm/Group Description Standard dose (20 mcg) of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. 40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. 20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. Total of all reporting groups
Overall Number of Baseline Participants 118 126 127 371
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 118 participants 126 participants 127 participants 371 participants
20.56  (3.42) 20.96  (3.25) 20.20  (3.50) 20.57  (3.40)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 118 participants 126 participants 127 participants 371 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
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 118 participants 126 participants 127 participants 371 participants
Female
73
  61.9%
74
  58.7%
80
  63.0%
227
  61.2%
Male
45
  38.1%
52
  41.3%
47
  37.0%
144
  38.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 118 participants 126 participants 127 participants 371 participants
United States 52 54 49 155
South Africa 4 6 13 23
Brazil 52 58 58 168
Bahamas 10 8 7 25
1.Primary Outcome
Title Sero-response to Hepatitis B Surface Antigen
Hide Description The primary outcome, percentage positive sero-response, was compared between Arm 1 and each of the two alternative strategy arms (Arm 2 and Arm 3) and measured 4 weeks after the third vaccination at Week 28. Response is defined as greater than or equal to 10 IU/mL of serum being present; non-response is defined as less than 10 IU/mL.
Time Frame Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who completed a Week 28 visit with a Hepatitis B serology result were included in this analysis.
Arm/Group Title 1: Engerix 20 mcg 2: Engerix 40 mcg 3: Twinrix 20 mcg
Hide Arm/Group Description:
Standard dose (20 mcg) of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
Overall Number of Participants Analyzed 106 112 118
Measure Type: Number
Unit of Measure: percentage of participants who resonded
60 73.2 75.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1: Engerix 20 mcg, 2: Engerix 40 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0440
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1: Engerix 20 mcg, 3: Twinrix 20 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0157
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
2.Secondary Outcome
Title Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - POSSIBLY OR PROBABLY RELATED
Hide Description The number of adverse events (AE) was described by study arm. The proportion of subjects with clinical adverse events 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 patients with any grade toxicity.
Time Frame Baseline through Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants were included in this analysis of all AEs that were possibly or probably related to study drug. There were no AEs above Grade 3 considered to be possibly or probably related to study drug.
Arm/Group Title 1: Engerix 20 mcg 2: Engerix 40 mcg 3: Twinrix 20 mcg
Hide Arm/Group Description:
Standard dose (20 mcg) of Hepatitis B vaccine. Number of participants with a Grade 1 event that was probably or possibly related to study drug as determined by the Site Investigator.
Engerix 40 mcg vaccine. Number of participants with a Grade 1 event that was probably or possibly related to study drug as determined by the Site Investigator.
Twinrix 20 mcg vaccine. Number of participants with a Grade 1 event that was probably or possibly related to study drug as determined by the Site Investigator.
Overall Number of Participants Analyzed 118 126 127
Measure Type: Number
Unit of Measure: Events
Asthenia, Grade 1 0 0 1
Arthralgia, Grade 3 1 0 0
Headache, Grade 1 1 0 0
Headache, Grade 2 2 0 0
Somnolence, Grade 1 0 0 1
Syncope Vasovagal, Grade 1 0 0 1
3.Secondary Outcome
Title Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - DEFINITELY RELATED
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 1: Engerix 20 mcg 2: Engerix 40 mcg 3: Twinrix 20 mcg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 118 126 127
Measure Type: Number
Unit of Measure: event
Injection Site Pain, Grade 1 1 0 1
Myalgia, Grade 2 1 0 1
4.Secondary Outcome
Title Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ABNORMAL LABORATORY VALUES GRADE 2 OR ABOVE BY INTERVENTION ARM ON STUDY
Hide Description The number of adverse events and subjects with the events were described by study arm. The proportion of subjects with abnormal labs 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 grade 3 or 4 toxicity. The laboratory events included are AEs classified as probably, possibly, or definitely related to study drug as classified by the Site Investigator.
Time Frame Baseline through Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants were included in this analysis. The following no. of participants experienced at least one Grade 2 or higher abnormal labs by study arm.
Arm/Group Title 1: Engerix 20 mcg 2: Engerix 40 mcg 3: Twindrix 20 mcg
Hide Arm/Group Description:
Standard dose (20 mcg) of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
Overall Number of Participants Analyzed 102 109 118
Overall Number of Units Analyzed
Type of Units Analyzed: Events
10 10 19
Measure Type: Number
Unit of Measure: Events
Absolute Neutrophil Count 7 5 9
Hemoglobin 0 1 2
Platelets 0 2 1
White Blood Cell count 3 2 7
5.Secondary Outcome
Title Response Rates in HIV+ Youth Within Each Study Arm by Study Duration
Hide Description Within each arm, the duration of response in HIV-infected youth was analyzed for all subjects who were responders at 28 weeks. The possible values for response duration could be 20 weeks or less (responder at 28 weeks but not at 48 weeks), 20 to 44 weeks (responder at 28 and 48 weeks but not at 72 weeks), or greater than 44 weeks (responder at 28, 48, and 72 weeks). A response of greater than 20 weeks includes those who responded after 20 weeks, but whose exact response duration was unknown.
Time Frame Entry through Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
Population analyzed were those who had an antibody titer measured at Week 28.
Arm/Group Title 1: Engerix 20 mcg 2: Engerix 40 mcg 3: Twinrix 20 mcg
Hide Arm/Group Description:
Standard dose (20 mcg) of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
Overall Number of Participants Analyzed 61 78 81
Measure Type: Number
Unit of Measure: percentage of participants who responded
<= 20 weeks 27.87 19.23 22.22
21 - 44 weeks 3.28 7.69 11.11
> 20 weeks 4.92 12.82 3.70
> 44 weeks 63.93 60.26 62.96
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1: Engerix 20 mcg, 2: Engerix 40 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5822
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.840
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1: Engerix 20 mcg, 3: Twinrix 20 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8698
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.050
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Sero-Response to Hepatitis B Surface Antigen; Predictor: STUDY ARM
Hide Description Response rate associated with the participant's study arm, baseline CD4 count, and interaction term that reflects how subjects in Arm 2 responded differently depending on their CD4 count. Response is defined as greater than or equal to 10 IU/mL of serum being present; non-response is defined as less than 10 IU/mL.
Time Frame Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who had a Week 28 Hepatitis B serology result
Arm/Group Title 2: Engerix 40 mcg 1: Engerix 20 mcg 3: Twinrix 20 mcg
Hide Arm/Group Description:
40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
Standard dose (20 mcg) of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
Overall Number of Participants Analyzed 112 106 118
Measure Type: Number
Unit of Measure: percentage of participants who responded
73.2 60 75.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2: Engerix 40 mcg, 1: Engerix 20 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0853
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.07 to 1.19
Estimation Comments Adjusted odds ratio (OR) Odds ratio depends on CD4 count resulting from interaction. For example, OR=0.29 for CD4 count = 0; OR= 2.91 for CD4 count = 460 (median CD4 count for the evaluable study population).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1: Engerix 20 mcg, 3: Twinrix 20 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0244
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.99
Confidence Interval (2-Sided) 95%
1.09 to 3.63
Estimation Comments Adjusted odds ratio
Time Frame Data were collected over a three year time period.
Adverse Event Reporting Description There were no Serious Adverse Events (SAE) to report
 
Arm/Group Title 1: Engerix 20 mcg 2: Engerix 40 mcg 3. Twinrix 20 mcg
Hide Arm/Group Description Standard dose (20 mcg) of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. 40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. 20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
All-Cause Mortality
1: Engerix 20 mcg 2: Engerix 40 mcg 3. Twinrix 20 mcg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
1: Engerix 20 mcg 2: Engerix 40 mcg 3. Twinrix 20 mcg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/118 (0.00%)      0/126 (0.00%)      0/127 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
1: Engerix 20 mcg 2: Engerix 40 mcg 3. Twinrix 20 mcg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   28/118 (23.73%)      25/126 (19.84%)      25/127 (19.69%)    
Blood and lymphatic system disorders       
Blood and lymphatic System Disorders   7/118 (5.93%)  7 5/126 (3.97%)  5 6/127 (4.72%)  6
Gastrointestinal disorders       
Gastrointestinal Disorders   4/118 (3.39%)  4 11/126 (8.73%)  11 1/127 (0.79%)  1
General disorders       
General Disorders and Administration Site Conditions   14/118 (11.86%)  14 3/126 (2.38%)  3 7/127 (5.51%)  7
Infections and infestations       
Infecions and Infestations   14/118 (11.86%)  14 12/126 (9.52%)  12 7/127 (5.51%)  7
Investigations       
Investigations   12/118 (10.17%)  12 5/126 (3.97%)  5 9/127 (7.09%)  9
Nervous system disorders       
Nervous System Disorders   17/118 (14.41%)  17 14/126 (11.11%)  14 12/127 (9.45%)  12
Indicates events were collected by systematic assessment
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 Adolescent Medicine Trials Network (ATN) for HIV/AIDS Interventions Publication Policy outlines procedures for the development and review of abstracts, publications and presentations. The Adolescent Medicine Leadership Group (AMLG) retains custody of and primary rights to the data. Use of data must be approved by protocol team and AMLG.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Bob Harris
Organization: Westat
Phone: 301-251-1500
EMail: bobharris@westat.com
Layout table for additonal information
Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00106964    
Other Study ID Numbers: ATN 024
First Submitted: April 1, 2005
First Posted: April 4, 2005
Results First Submitted: October 26, 2012
Results First Posted: June 28, 2013
Last Update Posted: March 29, 2017