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

NCT ID: NCT00106964

Last Updated: 2017-03-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 371 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2009-06-30

Brief Summary

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.

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:

1. standard adult dosing of HBV-only vaccine: Engerix-B 20 mcg at Entry, Week 4 and Week 24

2. increased adult dosing of HBV-only vaccine: Engerix-B 40 mcg at Entry, Week 4 and Week 24

3. 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

1

Standard dose (20 mcg) of Hepatitis B vaccine.

Group Type: ACTIVE_COMPARATOR

Engerix-B 20 mcg

Intervention Type: BIOLOGICAL

A single dose of 1 mL (20 mcg/mL) will be administered in the deltoid muscle at Entry, Weeks 4 and 24.

2

40 mcg of Hepatitis B vaccine

Group Type: ACTIVE_COMPARATOR

Engerix-B 40 mcg

Intervention Type: BIOLOGICAL

A single dose of 2 mL (20 mcg/mL) will be administered in the deltoid muscle at Entry, Week 4 and 24.

3

20 mgc of Twinrix

Group Type: ACTIVE_COMPARATOR

Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg

Intervention Type: BIOLOGICAL

Arm 3: 720 EIA HAV Ag, 20 mcg HBsAg/ml:

A single dose of 1 mL will be administered in the deltoid muscle.

Interventions

Engerix-B 20 mcg

A single dose of 1 mL (20 mcg/mL) will be administered in the deltoid muscle at Entry, Weeks 4 and 24.

Intervention Type: BIOLOGICAL

Engerix-B 40 mcg

A single dose of 2 mL (20 mcg/mL) will be administered in the deltoid muscle at Entry, Week 4 and 24.

Intervention Type: BIOLOGICAL

Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg

Arm 3: 720 EIA HAV Ag, 20 mcg HBsAg/ml:

A single dose of 1 mL will be administered in the deltoid muscle.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• 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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 24 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patricia Flynn, MD

Role: STUDY_CHAIR

St. Jude Children's Research Hospital

Patricia Emmanuel, MD

Role: PRINCIPAL_INVESTIGATOR

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

Diane M. Straub, MD

Role: PRINCIPAL_INVESTIGATOR

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

Jorge Lujuan-Ziberman, MD

Role: PRINCIPAL_INVESTIGATOR

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

Lawrence D'Angelo, MD

Role: PRINCIPAL_INVESTIGATOR

Children's National Medical Center, Div. of Aldol & Young Adult Medicine

Carleen Townsend-Akpan, CPNP

Role: PRINCIPAL_INVESTIGATOR

Children's National Medical Center, Div. of Aldol & Young Adult Medicine

Jaime Martinez, MD

Role: PRINCIPAL_INVESTIGATOR

John H. Stroger Jr. Hospital

Lisa Henry- Reid, MD

Role: PRINCIPAL_INVESTIGATOR

John H. Stroger Jr. Hospital

Irma Febo, MD

Role: PRINCIPAL_INVESTIGATOR

University Pediatric Hospital

LLeana Blasini, MD

Role: PRINCIPAL_INVESTIGATOR

University Pediatric Hospital

Donna Futterman, MD

Role: PRINCIPAL_INVESTIGATOR

Montefiore Medical Center

Marina Catallozzi, MD

Role: PRINCIPAL_INVESTIGATOR

Montifiore Medical Center

Linda Levin, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Barbara Moscicki, MD

Role: PRINCIPAL_INVESTIGATOR

Univ. of California at San Franciso

Coco Auerswald, MD

Role: PRINCIPAL_INVESTIGATOR

Univ. of California at San Franciso

Sue Ellen Abdalian, MD

Role: PRINCIPAL_INVESTIGATOR

Tulane Medical Center

Ligia Peralta, MD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland

Lawrence Friedman, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Ana Puga, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Diagnostic & Treatment Center

Stephen Spector, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Rolando M Viani, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

Childrens Hosp of Los Angeles

Los Angeles, California, United States

University of California at San Francisco

San Francisco, California, United States

Children's Hosp Natinal Med Center

Washington D.C., District of Columbia, United States

Tulane Med Center

New Orleans, Louisiana, United States

Federal University of Minas Gerais

Belo Horizonte, Minas Gerais, Brazil

Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto/USP

Ribeirão Preto, São Paulo, Brazil

Instituto de Infectologia Emilio Ribas

São Paulo, São Paulo, Brazil

Hospital dos Sevidores do Estado

Rio de Janeiro, , Brazil

Ippmg-Ufrj

Rio de Janeiro, , Brazil

Tygerberg Hospital

Bellville, Cape Town, South Africa

Harriet Shezi Childrens Clinic Chris Hani Baragwanth Hospital

Johannesburg, Gauteng, South Africa

Countries

United States; Brazil; South Africa

References

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.

Reference Type: RESULT

PMID: 21350366 (View on PubMed)

Related Links

http://www.atnonline.org

Website for the Adolescent Trials Network for HIV/AIDS Interventions

Other Identifiers

ATN 024

Identifier Type: -

Identifier Source: org_study_id