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	Treatment or Intervention	Phase
HIV Infection Hepatitis B	Vaccine: Engerix-B 20 mcg  Vaccine: Engerix-B 40 mcg  Vaccine: Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg	Phase IV

Further Study Details: 

Primary Outcomes: Determine sero-response to hepatitis B vaccine in HIV+ youth four weeks following standard adult dosing regimen versus two alternate regimens
Secondary Outcomes: 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
Expected Total Enrollment:  369

Suboptimal response to hepatitis B vaccination in HIV+ adults and children has been well documented in the literature. Given the importance of preventing HBV (hepatitis B virus) 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/HAV vaccine: Twinrix 720 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.

Ages Eligible for Study:  12 Years   -   24 Years,  Genders Eligible for Study:  Both

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-HBsAg, HBs-Ag or anti-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.

Dina Monte, BSN, CCRC      914-591-6170    dinamonte@westat.com

California
      Childrens Hosp of Los Angeles, Los Angeles,  California,  90054,  United States; Recruiting
District of Columbia
      Children's Hosp Natinal Med Center, Washington,  District of Columbia,  20010,  United States; Recruiting
Louisiana
      Tulane Med Center, New Orleans,  Louisiana,  70112,  United States; Recruiting

Study chairs or principal investigators

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   
Jorge Lujuan-Ziberman, MD,  Principal Investigator,  University of South Florida, Peds. Div. of Infectious Disease   
Lawrence D'Angelo, MD,  Principal Investigator,  Children's National Medical Center, Div. of Aldol & Young Adult Medicine   
Carleen Townsend-Akpan, CPNP,  Principal Investigator,  Children's National Medical Center, Div. of Aldol & Young Adult Medicine   
Jaime Martinez, MD,  Principal Investigator,  John H. Stroger Jr. Hospital   
Lisa Henry- Reid, MD,  Principal Investigator,  John H. Stroger Jr. Hospital   
Irma Febo, MD,  Principal Investigator,  University Pediatric Hospital   
LLeana Blasini, MD,  Principal Investigator,  University Pediatric Hospital   
Donna Futterman, MD,  Principal Investigator,  Montefiore Medical Center   
Marina Catallozzi, MD,  Principal Investigator,  Montifiore Medical Center   
Linda Levin, MD,  Principal Investigator,  Mount Sinai Medical Center   
Barbara Moscicki, MD,  Principal Investigator,  Univ. of California at San Franciso   
Coco Auerswald, MD,  Principal Investigator,  Univ. of California at San Franciso   
Sue Ellen Abdalian, MD,  Principal Investigator,  Tulane Medical Center   
Ligia Peralta, MD,  Principal Investigator,  University of Maryland   
Lawrence Friedman, MD,  Principal Investigator,  University of Miami School of Medicine   
Ana Puga, MD,  Principal Investigator,  Children's Diagnostic & Treatment Center   
Stephen Spector, MD,  Principal Investigator,  University of California at San Diego   
Rolando M Viani, MD,  Principal Investigator,  University of California at San Diego   

Study ID Numbers:  ATN 024
Record last reviewed:  March 2005
Last Updated:  April 4, 2005
Record first received:  April 1, 2005
ClinicalTrials.gov Identifier:  NCT00106964
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08