Trial Outcomes & Findings for Comparison of Three Hepatitis B Vaccination Regimens in HIV-Positive Youth (NCT NCT00106964)
NCT ID: NCT00106964
Last Updated: 2017-03-29
Results Overview
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.
COMPLETED
PHASE4
371 participants
Week 28
2017-03-29
Participant Flow
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.
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.
Participant milestones
| Measure |
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
118
|
126
|
127
|
|
Overall Study
COMPLETED
|
105
|
111
|
120
|
|
Overall Study
NOT COMPLETED
|
13
|
15
|
7
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
8
|
6
|
2
|
|
Overall Study
Pregnancy
|
2
|
3
|
2
|
|
Overall Study
Death
|
1
|
1
|
0
|
|
Overall Study
Incarceration
|
0
|
1
|
0
|
|
Overall Study
Site Funding Terminated
|
0
|
1
|
1
|
|
Overall Study
Failure to adhere
|
2
|
0
|
0
|
|
Overall Study
Did not meet eligibility criteria
|
0
|
2
|
2
|
|
Overall Study
Required disallowed medication
|
0
|
1
|
0
|
Baseline Characteristics
Comparison of Three Hepatitis B Vaccination Regimens in HIV-Positive Youth
Baseline characteristics by cohort
| Measure |
1: Engerix 20 mcg
n=118 Participants
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
n=126 Participants
40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
3: Twinrix 20 mcg
n=127 Participants
20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
Total
n=371 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
20.56 years
STANDARD_DEVIATION 3.42 • n=5 Participants
|
20.96 years
STANDARD_DEVIATION 3.25 • n=7 Participants
|
20.20 years
STANDARD_DEVIATION 3.50 • n=5 Participants
|
20.57 years
STANDARD_DEVIATION 3.40 • n=4 Participants
|
|
Age, Customized
12-13 years
|
8 participants
n=5 Participants
|
3 participants
n=7 Participants
|
8 participants
n=5 Participants
|
19 participants
n=4 Participants
|
|
Age, Customized
14-15 years
|
5 participants
n=5 Participants
|
11 participants
n=7 Participants
|
10 participants
n=5 Participants
|
26 participants
n=4 Participants
|
|
Age, Customized
16-19 years
|
25 participants
n=5 Participants
|
18 participants
n=7 Participants
|
20 participants
n=5 Participants
|
63 participants
n=4 Participants
|
|
Age, Customized
>20 years
|
80 participants
n=5 Participants
|
94 participants
n=7 Participants
|
89 participants
n=5 Participants
|
263 participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
73 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
80 Participants
n=5 Participants
|
227 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
45 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
144 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
52 participants
n=5 Participants
|
54 participants
n=7 Participants
|
49 participants
n=5 Participants
|
155 participants
n=4 Participants
|
|
Region of Enrollment
South Africa
|
4 participants
n=5 Participants
|
6 participants
n=7 Participants
|
13 participants
n=5 Participants
|
23 participants
n=4 Participants
|
|
Region of Enrollment
Brazil
|
52 participants
n=5 Participants
|
58 participants
n=7 Participants
|
58 participants
n=5 Participants
|
168 participants
n=4 Participants
|
|
Region of Enrollment
Bahamas
|
10 participants
n=5 Participants
|
8 participants
n=7 Participants
|
7 participants
n=5 Participants
|
25 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Week 28Population: Participants who completed a Week 28 visit with a Hepatitis B serology result were included in this analysis.
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.
Outcome measures
| Measure |
1: Engerix 20 mcg
n=106 Participants
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
n=112 Participants
40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
3: Twinrix 20 mcg
n=118 Participants
20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
|---|---|---|---|
|
Sero-response to Hepatitis B Surface Antigen
|
60 percentage of participants who resonded
Interval 0.0 to 0.0
|
73.2 percentage of participants who resonded
Interval 65.0 to 81.4
|
75.4 percentage of participants who resonded
Interval 67.7 to 83.2
|
SECONDARY outcome
Timeframe: Baseline through Week 72Population: 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.
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.
Outcome measures
| Measure |
1: Engerix 20 mcg
n=118 Participants
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
n=126 Participants
40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
3: Twinrix 20 mcg
n=127 Participants
20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
|---|---|---|---|
|
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - POSSIBLY OR PROBABLY RELATED
Asthenia, Grade 1
|
0 Events
|
0 Events
|
1 Events
|
|
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - POSSIBLY OR PROBABLY RELATED
Arthralgia, Grade 3
|
1 Events
|
0 Events
|
0 Events
|
|
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - POSSIBLY OR PROBABLY RELATED
Headache, Grade 1
|
1 Events
|
0 Events
|
0 Events
|
|
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - POSSIBLY OR PROBABLY RELATED
Headache, Grade 2
|
2 Events
|
0 Events
|
0 Events
|
|
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - POSSIBLY OR PROBABLY RELATED
Somnolence, Grade 1
|
0 Events
|
0 Events
|
1 Events
|
|
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - POSSIBLY OR PROBABLY RELATED
Syncope Vasovagal, Grade 1
|
0 Events
|
0 Events
|
1 Events
|
SECONDARY outcome
Timeframe: Baseline through Week 72Population: 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.
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.
Outcome measures
| Measure |
1: Engerix 20 mcg
n=118 Participants
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
n=126 Participants
40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
3: Twinrix 20 mcg
n=127 Participants
20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
|---|---|---|---|
|
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - DEFINITELY RELATED
Injection Site Pain, Grade 1
|
1 event
|
0 event
|
1 event
|
|
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - DEFINITELY RELATED
Myalgia, Grade 2
|
1 event
|
0 event
|
1 event
|
SECONDARY outcome
Timeframe: Baseline through Week 72Population: 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.
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.
Outcome measures
| Measure |
1: Engerix 20 mcg
n=10 Events
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
n=10 Events
40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
3: Twinrix 20 mcg
n=19 Events
20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
|---|---|---|---|
|
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ABNORMAL LABORATORY VALUES GRADE 2 OR ABOVE BY INTERVENTION ARM ON STUDY
Absolute Neutrophil Count
|
7 Events
|
5 Events
|
9 Events
|
|
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ABNORMAL LABORATORY VALUES GRADE 2 OR ABOVE BY INTERVENTION ARM ON STUDY
Hemoglobin
|
0 Events
|
1 Events
|
2 Events
|
|
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ABNORMAL LABORATORY VALUES GRADE 2 OR ABOVE BY INTERVENTION ARM ON STUDY
Platelets
|
0 Events
|
2 Events
|
1 Events
|
|
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ABNORMAL LABORATORY VALUES GRADE 2 OR ABOVE BY INTERVENTION ARM ON STUDY
White Blood Cell count
|
3 Events
|
2 Events
|
7 Events
|
SECONDARY outcome
Timeframe: Entry through Week 72Population: Population analyzed were those who had an antibody titer measured at Week 28.
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.
Outcome measures
| Measure |
1: Engerix 20 mcg
n=61 Participants
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
n=78 Participants
40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
3: Twinrix 20 mcg
n=81 Participants
20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
|---|---|---|---|
|
Response Rates in HIV+ Youth Within Each Study Arm by Study Duration
<= 20 weeks
|
27.87 percentage of participants who responded
|
19.23 percentage of participants who responded
|
22.22 percentage of participants who responded
|
|
Response Rates in HIV+ Youth Within Each Study Arm by Study Duration
21 - 44 weeks
|
3.28 percentage of participants who responded
|
7.69 percentage of participants who responded
|
11.11 percentage of participants who responded
|
|
Response Rates in HIV+ Youth Within Each Study Arm by Study Duration
> 20 weeks
|
4.92 percentage of participants who responded
|
12.82 percentage of participants who responded
|
3.70 percentage of participants who responded
|
|
Response Rates in HIV+ Youth Within Each Study Arm by Study Duration
> 44 weeks
|
63.93 percentage of participants who responded
|
60.26 percentage of participants who responded
|
62.96 percentage of participants who responded
|
SECONDARY outcome
Timeframe: Week 28Population: All participants who had a Week 28 Hepatitis B serology result
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.
Outcome measures
| Measure |
1: Engerix 20 mcg
n=112 Participants
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
n=106 Participants
40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
3: Twinrix 20 mcg
n=118 Participants
20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
|---|---|---|---|
|
Sero-Response to Hepatitis B Surface Antigen; Predictor: STUDY ARM
|
73.2 percentage of participants who responded
Interval 0.07 to 1.19
|
60 percentage of participants who responded
Interval 1.0 to 1.0
|
75.4 percentage of participants who responded
Interval 1.09 to 3.63
|
Adverse Events
1: Engerix 20 mcg
2: Engerix 40 mcg
3. Twinrix 20 mcg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
1: Engerix 20 mcg
n=118 participants at risk
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
n=126 participants at risk
40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
3. Twinrix 20 mcg
n=127 participants at risk
20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24.
|
|---|---|---|---|
|
General disorders
General Disorders and Administration Site Conditions
|
11.9%
14/118 • Number of events 14 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
2.4%
3/126 • Number of events 3 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
5.5%
7/127 • Number of events 7 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
|
Nervous system disorders
Nervous System Disorders
|
14.4%
17/118 • Number of events 17 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
11.1%
14/126 • Number of events 14 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
9.4%
12/127 • Number of events 12 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
|
Gastrointestinal disorders
Gastrointestinal Disorders
|
3.4%
4/118 • Number of events 4 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
8.7%
11/126 • Number of events 11 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
0.79%
1/127 • Number of events 1 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
|
Investigations
Investigations
|
10.2%
12/118 • Number of events 12 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
4.0%
5/126 • Number of events 5 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
7.1%
9/127 • Number of events 9 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
|
Blood and lymphatic system disorders
Blood and lymphatic System Disorders
|
5.9%
7/118 • Number of events 7 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
4.0%
5/126 • Number of events 5 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
4.7%
6/127 • Number of events 6 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
|
Infections and infestations
Infecions and Infestations
|
11.9%
14/118 • Number of events 14 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
9.5%
12/126 • Number of events 12 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
5.5%
7/127 • Number of events 7 • Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER