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

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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 Description
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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.

Condition or disease Intervention/treatment Phase
HIV Infection Hepatitis B Biological: Engerix-B 20 mcg Biological: Engerix-B 40 mcg Biological: Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg Phase 4

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.


Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 371 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Randomized, Open-Label Trial of Three Hepatitis B Vaccination Schemas in HIV-Positive Youth
Study Start Date : January 2004
Actual Primary Completion Date : January 2008
Actual Study Completion Date : June 2009

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U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: 1
Standard dose (20 mcg) of Hepatitis B vaccine.
 Biological: 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.
Active Comparator: 2
40 mcg of Hepatitis B vaccine
 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.
Active Comparator: 3
20 mgc of Twinrix
 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.


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. 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 ]
    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.

  3. 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 ]
    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.

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

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


Eligibility Criteria
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Ages Eligible for Study:   12 Years to 24 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00106964


Locations
United States, California
Childrens Hosp of Los Angeles
Los Angeles, California, United States, 90054
University of California at San Francisco
San Fransisco, California, United States, 94118
United States, District of Columbia
Children's Hosp Natinal Med Center
Washington, District of Columbia, United States, 20010
United States, Louisiana
Tulane Med Center
New Orleans, Louisiana, United States, 70112
Brazil
Federal University of Minas Gerais
Belo Horizonte, MG, Brazil, 30130-100
Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto/USP
Ribeirao Preto, SP, Brazil, 14049-900
Instituto de Infectologia Emilio Ribas
Sao Paulo, SP, Brazil, 01246-900
Hospital dos Sevidores do Estado
Rio de Janeiro, Brazil, 20221-903
Ippmg-Ufrj
Rio de Janeiro, Brazil, 21941590
South Africa
Tygerberg Hospital
Bellville, Cape Town, South Africa, 7505
Harriet Shezi Childrens Clinic Chris Hani Baragwanth Hospital
Johannesburg, Gauteng, South Africa, 2013
Sponsors and Collaborators
University of North Carolina, Chapel Hill
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
Study Chair: Patricia Flynn, MD St. Jude Children's Research Hospital
Principal Investigator: Patricia Emmanuel, MD University of South Florida, Peds. Div. of Infectious Disease
Principal Investigator: Diane M. Straub, MD University of South Florida, Peds. Div. of Infectious Disease
Principal Investigator: Jorge Lujuan-Ziberman, MD University of South Florida, Peds. Div. of Infectious Disease
Principal Investigator: Lawrence D'Angelo, MD Children's National Medical Center, Div. of Aldol & Young Adult Medicine
Principal Investigator: Carleen Townsend-Akpan, CPNP Children's National Medical Center, Div. of Aldol & Young Adult Medicine
Principal Investigator: Jaime Martinez, MD John H. Stroger Jr. Hospital
Principal Investigator: Lisa Henry- Reid, MD John H. Stroger Jr. Hospital
Principal Investigator: Irma Febo, MD University Pediatric Hospital
Principal Investigator: LLeana Blasini, MD University Pediatric Hospital
Principal Investigator: Donna Futterman, MD Montefiore Medical Center
Principal Investigator: Marina Catallozzi, MD Montifiore Medical Center
Principal Investigator: Linda Levin, MD Icahn School of Medicine at Mount Sinai
Principal Investigator: Barbara Moscicki, MD Univ. of California at San Franciso
Principal Investigator: Coco Auerswald, MD Univ. of California at San Franciso
Principal Investigator: Sue Ellen Abdalian, MD Tulane Medical Center
Principal Investigator: Ligia Peralta, MD University of Maryland
Principal Investigator: Lawrence Friedman, MD University of Miami
Principal Investigator: Ana Puga, MD Children's Diagnostic & Treatment Center
Principal Investigator: Stephen Spector, MD University of California, San Diego
Principal Investigator: Rolando M Viani, MD University of California, San Diego
More Information
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Additional Information:
Website for the Adolescent Trials Network for HIV/AIDS Interventions  This link exits the ClinicalTrials.gov site

Publications of Results:

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00106964     History of Changes
Other Study ID Numbers: ATN 024
First Posted: April 4, 2005    Key Record Dates
Results First Posted: June 28, 2013
Last Update Posted: March 29, 2017
Last Verified: February 2016

Keywords provided by University of North Carolina, Chapel Hill:
Hepatitis B vaccines
HIV-infected adolescents
Hepatitis B infection (negative)

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
HIV Infections
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
 Lentivirus Infections
Retroviridae Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Hepadnaviridae Infections
DNA Virus Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs