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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infection; Hepatitis B
• Intervention / Treatment: Biological: Engerix-B 20 mcg; Biological: Engerix-B 40 mcg; Biological: Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg

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 Type: Interventional
• Enrollment (Actual): 371
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 20221-903
    • Hospital dos Sevidores do Estado
  • Rio de Janeiro, Brazil, 21941590
    • Ippmg-Ufrj
  • MG
    • Belo Horizonte, MG, Brazil, 30130-100
      • Federal University of Minas Gerais
  • SP
    • Ribeirao Preto, SP, Brazil, 14049-900
      • Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto/USP
    • Sao Paulo, SP, Brazil, 01246-900
      • Instituto de Infectologia Emilio Ribas
• South Africa
  • Cape Town
    • Bellville, Cape Town, South Africa, 7505
      • Tygerberg hospital
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2013
      • Harriet Shezi Childrens Clinic Chris Hani Baragwanth Hospital
• United States
  • California
    • Los Angeles, California, United States, 90054
      • Childrens Hosp of Los Angeles
    • San Fransisco, California, United States, 94118
      • University of California at San Francisco
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's Hosp Natinal Med Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Med Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 24 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	Week 28

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute on Drug Abuse (NIDA); National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute of Mental Health (NIMH)
• Investigators: 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

Publications and helpful links

General 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.

Helpful Links

• Website for the Adolescent Trials Network for HIV/AIDS Interventions

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: April 1, 2005
• First Submitted That Met QC Criteria: April 1, 2005
• First Posted (Estimate): April 4, 2005

Study Record Updates

• Last Update Posted (Actual): March 29, 2017
• Last Update Submitted That Met QC Criteria: February 27, 2017
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: HIV-infected adolescents; Hepatitis B vaccines; Hepatitis B infection (negative)
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A
• Other Study ID Numbers: ATN 024