Clinical trial NCT00106964: Comparison of Three Hepatitis B Vaccination Regimens in HIV-Positive Youth
Official title: A Randomized, Open-Label Trial of Three Hepatitis B Vaccination Schemas in HIV-Positive Youth
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infection
Hepatitis B
Keywords: Hepatitis B vaccines
HIV-infected adolescents
Hepatitis B infection (negative)
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: National Institute of Mental Health (NIMH)
name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2005-04-04
Enrollment: 371
Sex: ALL
Minimum age (years): 12
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Sero-response to Hepatitis B Surface Antigen
timeFrame: Week 28
Secondary outcomes:
measure: Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - POSSIBLY OR PROBABLY RELATED
timeFrame: Baseline through Week 72
measure: Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - DEFINITELY RELATED
timeFrame: Baseline through Week 72
measure: Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ABNORMAL LABORATORY VALUES GRADE 2 OR ABOVE BY INTERVENTION ARM ON STUDY
timeFrame: Baseline through Week 72
measure: Response Rates in HIV+ Youth Within Each Study Arm by Study Duration
timeFrame: Entry through Week 72
measure: Sero-Response to Hepatitis B Surface Antigen; Predictor: STUDY ARM
timeFrame: Week 28
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hosp of Los Angeles
state: California
city: San Fransisco
country: United States
facility: University of California at San Francisco
state: California
city: Washington
country: United States
facility: Children's Hosp Natinal Med Center
state: District of Columbia
city: New Orleans
country: United States
facility: Tulane Med Center
state: Louisiana
city: Belo Horizonte
country: Brazil
facility: Federal University of Minas Gerais
state: MG
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto/USP
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto de Infectologia Emilio Ribas
state: SP
city: Rio de Janeiro
country: Brazil
facility: Hospital dos Sevidores do Estado
city: Rio de Janeiro
country: Brazil
facility: Ippmg-Ufrj
city: Bellville
country: South Africa
facility: Tygerberg Hospital
state: Cape Town
city: Johannesburg
country: South Africa
facility: Harriet Shezi Childrens Clinic Chris Hani Baragwanth Hospital
state: Gauteng
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Patricia Flynn, MD
role: STUDY_CHAIR
affiliation: University of South Florida, Peds. Div. of Infectious Disease
name: Patricia Emmanuel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of South Florida, Peds. Div. of Infectious Disease
name: Diane M. Straub, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of South Florida, Peds. Div. of Infectious Disease
name: Jorge Lujuan-Ziberman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's National Medical Center, Div. of Aldol & Young Adult Medicine
name: Lawrence D'Angelo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's National Medical Center, Div. of Aldol & Young Adult Medicine
name: Carleen Townsend-Akpan, CPNP
role: PRINCIPAL_INVESTIGATOR
affiliation: John H. Stroger Jr. Hospital
name: Jaime Martinez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: John H. Stroger Jr. Hospital
name: Lisa Henry- Reid, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Pediatric Hospital
name: Irma Febo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Pediatric Hospital
name: LLeana Blasini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montefiore Medical Center
name: Donna Futterman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montifiore Medical Center
name: Marina Catallozzi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Linda Levin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Univ. of California at San Franciso
name: Barbara Moscicki, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Univ. of California at San Franciso
name: Coco Auerswald, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tulane Medical Center
name: Sue Ellen Abdalian, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Maryland
name: Ligia Peralta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Miami
name: Lawrence Friedman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Diagnostic & Treatment Center
name: Ana Puga, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Stephen Spector, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Rolando M Viani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.