HIV InfectionPhase 4NCT00106964

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

A Phase 4 study testing Engerix-B 20 mcg, Engerix-B 40 mcg and Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg in people with HIV Infection and Hepatitis B, run by University of North Carolina, Chapel Hill at 11 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 12 to 24 years
Conditions the study is for: HIV Infection, Hepatitis B
What is being tested?: Engerix-B 20 mcg, Engerix-B 40 mcg and Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 371 participants
Where: 11 sitesin 3 countries
Study dates: Jan 2004to Jun 2009
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 to 24 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Documented HIV+
Age 12 to < 25 years
History of no or one hepatitis B vaccination
Not pregnant.
Females engaging in sexual intercourse must be willing to practice an approved method of birth control throughout the completion of the vaccine phase of the study.

Who cannot join

History of > 1 hepatitis B vaccination
Serologic evidence of past or present hepatitis B infection: anti-hepatitis B surface antigen (HBsAg), HBs-Ag or anti- hepatitis B core antigen (HBcAg)
Previous allergic reaction to hepatitis A or B vaccinations or to yeast, thimerosal or aluminum.
Active opportunistic infection or current treatment for known or suspected active serious bacterial infection at the pre-entry exam.
Presence of any known grade >= 3 clinical or laboratory toxicity at the time of pre-entry per toxicity tables.
Anticipation of long-term corticosteroid therapy or within 3 months preceding study randomization. Use of non-steroidal, anti-inflammatory agents and inhaled or topical corticosteroids are allowed.

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Receipt of any restricted medicine listed in the protocol section 8.1.3 within 3 months preceding randomization.
Receipt of immune globulin product or plasma product within 6 months preceding randomization
Receipt of licensed blood product or transfusion or any licensed vaccine within 4 weeks preceding randomization.
Known or suspected diseases of the immune system, other than HIV, or treatment for a malignancy within 3 months of randomization.
Other serious, acute or chronic medical or surgical conditions must be approved by the protocol chair.

Trial locations and contacts

11 sites in 3 countries.

Country

City, postcode or hospital

11 sites in 3 countries

Brazil5 sites

Federal University of Minas Gerais
Belo Horizonte, Minas Gerais, 30130-100
Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto/USP
Ribeirão Preto, São Paulo, 14049-900
Hospital dos Sevidores do Estado
Rio de Janeiro, 20221-903
Ippmg-Ufrj
Rio de Janeiro, 21941590
Instituto de Infectologia Emilio Ribas
São Paulo, São Paulo, 01246-900

Other trials in Brazil

United States4 sites

Childrens Hosp of Los Angeles
Los Angeles, California, 90054
Tulane Med Center
New Orleans, Louisiana, 70112
University of California at San Francisco
San Francisco, California, 94118
Children's Hosp Natinal Med Center
Washington D.C., District of Columbia, 20010

Other trials in United States

South Africa2 sites

Tygerberg Hospital
Bellville, Cape Town, 7505
Harriet Shezi Childrens Clinic Chris Hani Baragwanth Hospital
Johannesburg, Gauteng, 2013

Other trials in South Africa

About this study

Official title: A Randomized, Open-Label Trial of Three Hepatitis B Vaccination Schemas in HIV-Positive Youth

Hepatitis B is a contagious virus that can damage a person's liver. It can be prevented by vaccination, but for many HIV-positive people, the vaccines do not help them achieve adequate protection against this virus. In an attempt to improve response to vaccination and achieve protection from hepatitis B, this trial will compare the immune system response to 3 hepatitis B vaccine regimens in HIV-positive adolescents 12 through 24 years of age.

Read the detailed description

Suboptimal response to hepatitis B vaccination in HIV+ adults and children has been well documented in the literature. Given the importance of preventing hepatitis B virus (HBV) co-infection in HIV+ youth and the poor response rates in this population, this study will attempt to improve the immediate and long-term sero-response rates by undertaking a randomized, open-label trial of three hepatitis B vaccination schemas, as follows:

standard adult dosing of HBV-only vaccine: Engerix-B 20 mcg at Entry, Week 4 and Week 24
increased adult dosing of HBV-only vaccine: Engerix-B 40 mcg at Entry, Week 4 and Week 24
standard adult dosing of combined HBV/hepatitis A virus (HAV) vaccine: Twinrix 720 enzyme immunoassay (EIA) HAV Ag plus 20 mcg HBsAg at Entry, Week 4 and Week 24.

This study will also describe the safety of administration of an increased dose of the hepatitis B vaccine in this population. In general, patients undergoing dialysis who have received the dosing regimen recommended for immunocompromised individuals have tolerated the vaccine series well.

Design: This is a stratified, block-randomized, open-label trial of three hepatitis B vaccination schemas in HIV-infected and HBV-uninfected youth. Once randomized, there will be a total of 6 study visits in a 72 week period. Vaccination will occur at Entry, Week 4 and Week 24. Primary sero-response will be evaluated at Week 28 and sustainability of response will be evaluated at Weeks 48 and 72 for those who achieve a primary antibody response of >= 10 IU/ml. Primary non-responders (antibody response of < 10 IU/ml) will be provided with a booster vaccine using the increased-dose Engerix-B vaccine at Week 48 and evaluated for responsiveness at Week 72.

Conditions: HIV Infection, Hepatitis B
Being tested: Engerix-B 20 mcg, Engerix-B 40 mcg, Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg
Keywords: Hepatitis B vaccines, HIV-infected adolescents, Hepatitis B infection (negative)
Medical subject headings: HIV Infections, Hepatitis B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Engerix-B 20 mcgBiological
A single dose of 1 mL (20 mcg/mL) will be administered in the deltoid muscle at Entry, Weeks 4 and 24.
Engerix-B 40 mcgBiological
A single dose of 2 mL (20 mcg/mL) will be administered in the deltoid muscle at Entry, Week 4 and 24.
Twinrix 720 EIA HAV Ag plus 20 mcg HBsAgBiological
Arm 3: 720 EIA HAV Ag, 20 mcg HBsAg/ml:
A single dose of 1 mL will be administered in the deltoid muscle.

Study groups in NCT00106964
Study group	Role	What they receive
1	Active comparator	Standard dose (20 mcg) of Hepatitis B vaccine. Receives: Biological: Engerix-B 20 mcg
2	Active comparator	40 mcg of Hepatitis B vaccine Receives: Biological: Engerix-B 40 mcg
3	Active comparator	20 mgc of Twinrix Receives: Biological: Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg

What is being measured

The primary outcome is the main question the study is designed to answer.

Sero-response to Hepatitis B Surface Antigen
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.
Measured: Week 28

Secondary outcomes (5)

Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - POSSIBLY OR PROBABLY RELATED
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.
Measured: Baseline through Week 72
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - DEFINITELY RELATED
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.
Measured: Baseline through Week 72
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ABNORMAL LABORATORY VALUES GRADE 2 OR ABOVE BY INTERVENTION ARM ON STUDY
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.
Measured: Baseline through Week 72
Response Rates in HIV+ Youth Within Each Study Arm by Study Duration
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.
Measured: Entry through Week 72
Sero-Response to Hepatitis B Surface Antigen; Predictor: STUDY ARM
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.
Measured: Week 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2004Jun 2009

First posted4 Apr 2005 (estimated)
Study startJan 2004
Primary completionJan 2008
Study completionJun 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIV InfectionStudies of the same condition, open and under way.
More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 371 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00106964
Sponsor's protocol ID: ATN 024
Status last verified: Feb 2016
First submitted: 1 Apr 2005
Last updated: 29 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Flynn PM, Cunningham CK, Rudy B, Wilson CM, Kapogiannis B, Worrell C, Bethel J, Monte D, Bojan K; Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN). Hepatitis B vaccination in HIV-infected youth: a randomized trial of three regimens. J Acquir Immune Defic Syndr. 2011 Apr;56(4):325-32. doi: 10.1097/QAI.0b013e318203e9f2.
PubMed 21350366

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 29 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Open-Label Trial of Three Hepatitis B Vaccination Schemas in HIV-Positive Youth
ClinicalTrials.gov ID: NCT00106964
Acronym / sponsor ID: ATN 024
Conditions: HIV Infection, Hepatitis B
Keywords: Hepatitis B vaccines, HIV-infected adolescents, Hepatitis B infection (negative)
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 371 participants (actual)
Lead sponsor: University of North Carolina, Chapel HillUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH), National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Study start: Jan 2004
Primary completion: Jan 2008 (actual)
Study completion: Jun 2009 (actual)
First posted: 4 Apr 2005 (estimated)
Results: Posted 28 Jun 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

standard adult dosing of HBV-only vaccine: Engerix-B 20 mcg at Entry, Week 4 and Week 24
increased adult dosing of HBV-only vaccine: Engerix-B 40 mcg at Entry, Week 4 and Week 24
standard adult dosing of combined HBV/hepatitis A virus (HAV) vaccine: Twinrix 720 enzyme immunoassay (EIA) HAV Ag plus 20 mcg HBsAg at Entry, Week 4 and Week 24.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
1	Active comparator	Biological: Engerix-B 20 mcgStandard dose (20 mcg) of Hepatitis B vaccine.
2	Active comparator	Biological: Engerix-B 40 mcg40 mcg of Hepatitis B vaccine
3	Active comparator	Biological: Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg20 mgc of Twinrix

Who may qualify

Ages: 12 to 24 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (5 listed)

Documented HIV+
Age 12 to < 25 years
History of no or one hepatitis B vaccination
Not pregnant.
Females engaging in sexual intercourse must be willing to practice an approved method of birth control throughout the completion of the vaccine phase of the study.

Key exclusion criteria (11 listed)

History of > 1 hepatitis B vaccination
Serologic evidence of past or present hepatitis B infection: anti-hepatitis B surface antigen (HBsAg), HBs-Ag or anti- hepatitis B core antigen (HBcAg)
Previous allergic reaction to hepatitis A or B vaccinations or to yeast, thimerosal or aluminum.
Active opportunistic infection or current treatment for known or suspected active serious bacterial infection at the pre-entry exam.
Presence of any known grade >= 3 clinical or laboratory toxicity at the time of pre-entry per toxicity tables.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Engerix-B 20 mcgA single dose of 1 mL (20 mcg/mL) will be administered in the deltoid muscle at Entry, Weeks 4 and 24.	Biological	1
Engerix-B 40 mcgA single dose of 2 mL (20 mcg/mL) will be administered in the deltoid muscle at Entry, Week 4 and 24.	Biological	2
Twinrix 720 EIA HAV Ag plus 20 mcg HBsAgArm 3: 720 EIA HAV Ag, 20 mcg HBsAg/ml: A single dose of 1 mL will be administered in the deltoid muscle.	Biological	3

Primary outcome

Sero-response to Hepatitis B Surface Antigen
Time frame: Week 28
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.

5 secondary outcomes

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
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
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
Response Rates in HIV+ Youth Within Each Study Arm by Study Duration
Time frame: Entry through Week 72
Sero-Response to Hepatitis B Surface Antigen; Predictor: STUDY ARM
Time frame: Week 28

Results and safety

Results posted to the registry on 28 Jun 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
1: Engerix 20 mcg	118	105
2: Engerix 40 mcg	126	111
3: Twinrix 20 mcg	127	120

Primary outcome: Sero-response to Hepatitis B Surface Antigen

Time frame: Week 28. Number. Unit: percentage of participants who resonded

Measure	1: Engerix 20 mcg n = 106	2: Engerix 40 mcg n = 112	3: Twinrix 20 mcg n = 118
Value	60 (0.00 to 0.00)	73.2 (65 to 81.4)	75.4 (67.7 to 83.2)

1: Engerix 20 mcg vs 2: Engerix 40 mcg: p = 0.0440, Chi-squared
1: Engerix 20 mcg vs 3: Twinrix 20 mcg: p = 0.0157, Chi-squared

Population analysed: Participants who completed a Week 28 visit with a Hepatitis B serology result were included in this analysis.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Data were collected over a three year time period.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
1: Engerix 20 mcg	0 of 118 (0%)	28 of 118 (23.7%)	Not reported
2: Engerix 40 mcg	0 of 126 (0%)	25 of 126 (19.8%)	Not reported
3. Twinrix 20 mcg	0 of 127 (0%)	25 of 127 (19.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21350366Flynn PM, Cunningham CK, Rudy B, Wilson CM, Kapogiannis B, Worrell C, Bethel J, Monte D, Bojan K; Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN). Hepatitis B vaccination in HIV-infected youth: a randomized trial of three regimens. J Acquir Immune Defic Syndr. 2011 Apr;56(4):325-32. doi: 10.1097/QAI.0b013e318203e9f2.
Website for the Adolescent Trials Network for HIV/AIDS InterventionsLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Patricia Flynn, MD study chair

St. Jude Children's Research Hospital

Patricia Emmanuel, MD principal investigator

University of South Florida, Peds. Div. of Infectious Disease

Diane M. Straub, MD principal investigator

University of South Florida, Peds. Div. of Infectious Disease

11 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Brazil, United States, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Sero-response to Hepatitis B Surface Antigen (time frame: Week 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00106964, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2017.