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

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00106964
First received: April 1, 2005
Last updated: June 23, 2014
Last verified: April 2014

April 1, 2005
June 23, 2014
January 2004
January 2008   (final data collection date for primary outcome measure)
Sero-response to Hepatitis B Surface Antigen [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
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.
Determine sero-response to hepatitis B vaccine in HIV+ youth four weeks following standard adult dosing regimen versus two alternate regimens
Complete list of historical versions of study NCT00106964 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: Yes ]
    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.
  • 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 ] [ Designated as safety issue: Yes ]
    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.
  • 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 ] [ Designated as safety issue: Yes ]
    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.
  • Response Rates in HIV+ Youth Within Each Study Arm by Study Duration [ Time Frame: Entry through Week 72 ] [ Designated as safety issue: No ]
    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.
  • Sero-Response to Hepatitis B Surface Antigen; Predictor: STUDY ARM [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    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.
  • Determine the safety of 3 hepatitis B vaccine regimens in HIV+ youth
  • Determine the duration of response in HIV+ youth
  • Explore the virologic and immunologic factors that are related to sero-response (sub group analysis)
  • Assess the impact that missing data might have had on the results of the primary analysis
Not Provided
Not Provided
 
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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
  • HIV Infection
  • Hepatitis B
  • 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.
  • 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.
  • 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.

  • Active Comparator: 1
    Standard dose (20 mcg) of Hepatitis B vaccine.
    Intervention: Biological: Engerix-B 20 mcg
  • Active Comparator: 2
    40 mcg of Hepatitis B vaccine
    Intervention: Biological: Engerix-B 40 mcg
  • Active Comparator: 3
    20 mgc of Twinrix
    Intervention: Biological: Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
371
June 2009
January 2008   (final data collection date for primary outcome measure)

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.
Both
12 Years to 24 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Brazil,   South Africa
 
NCT00106964
ATN 024
Yes
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • National Institute on Drug Abuse (NIDA)
  • National Institute of Mental Health (NIMH)
  • National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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 Mount Sinai School of Medicine
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
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP