Clinical trial NCT00107042: Effectiveness of Two Hepatitis B Vaccines in HIV-negative Youths
Official title: Hepatitis B Vaccination in Youth at Adolescent Trial Network Sites: Effectiveness of Two Strategies and Evaluation of Tools To be Used in Future HIV Prevention Trials.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B
Keywords: Hepatitis B
HIV vaccine trial
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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: 2005-04-05
Enrollment: 123
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will evaluate 2 licensed vaccine products (Recombivax and Twinrix) given in a two-dose schedule to youth at risk for hepatitis B and HIV infection to evaluate immunogenicity of the products in this population, barriers to vaccine delivery, and factors which predict a diminished immune response. Since these youths are also potential candidates for future HIV vaccine trials, this study will also include preliminary assessment of youths' understanding of informed consent forms, and willingness to participate in a vaccine trial and return for multiple visits (including blood draws for immunologic assessment).

Detailed description: Hepatitis B (HBV) prophylactic immunization has been recommended for at-risk adolescents for more than 10 years although universal coverage has not been achieved. Vaccine response in healthy adolescents has generally been reported to be excellent. But, data from the study Reaching for Excellence in Adolescent Care and Health (REACH) that studied HIV-negative adolescents who were at-risk of acquiring Hepatitis B infection through sexual or needle sharing behaviors has demonstrated a much lower than expected vaccine response rate in this population using standard vaccine dosing. Some data suggest that factors such as gender or body mass index might be responsible for the differences in response to the vaccine observed in individuals. The reason for the diminished vaccine response in this population is unclear. If in fact, Hepatitis B vaccine response is diminished in this population, then efforts to determine correlates of response and to improve the response are warranted. The proposed trial will evaluate 2 licensed vaccine products given in a two-dose schedule in youth at risk for hepatitis B and HIV infection to evaluate immunogenicity of the products in this population, barriers to vaccine delivery, and factors which predict a diminished immune response.

Since these youths are also potential candidates for future HIV vaccine trials, participation in such trials will require ability to understand and willingness to volunteer for such trials, ability to return for multiple vaccinations and blood draws to assess vaccine response, and willingness to participate in HIV prevention education. A hepatitis B vaccine trial will provide a licensed vaccine to youth in whom the vaccine is indicated and will allow preliminary assessment of youth's willingness to participate in a vaccine trial that involves blood draws for immunologic assessment.

Tools that will be necessary for HIV vaccine trials in youth include a youth-friendly simplified vaccine trial education component with a required written test for the participant, a standardized risk reduction education program, and a computer-assisted assessment of youth behaviors. These tools can be finalized and field tested in youth participating in the hepatitis B vaccine trial without promoting a false sense of protection from HIV. Secondary objectives of this trial will include assessment of a number of ancillary tools crucial for future HIV vaccine trials. This Hepatitis B vaccine trial will also serve as a HIV vaccine preparedness trial for youth at risk for both Hepatitis B and HIV.

Design: This is a phase II, randomized, single-blinded trial of two hepatitis B immunization regimens in 150 HIV-negative, hepatitis B core antibody, hepatitis B surface antigen and surface antibody negative youth. Vaccinations will be given in a two-dose regimen at 0 and six months (75 subjects in each arm) and the primary outcome will be seroresponsiveness one month after the 6-month dose. Safety and tolerability will also be assessed.

Eligibility criteria: Inclusion Criteria:

* HIV negative youth age 12-17 years (No serologic evidence of HIV infection).
* Negative hepatitis B serology. (No serologic evidence of hepatitis B surface antigen (HBSAg), hepatitis B surface antibody (HBsAb or anti-HBs) and hepatitis B core antibody (HBcAb or anti-HBc)).
* Either no prior hepatitis B immunizations or unknown or incomplete hepatitis B immunization status.
* Willing to participate in HIV risk-reduction counseling and computer assisted measurement of behaviors.
* Parent or legal guardian willing to provide written permission
* Females of childbearing potential must have a negative pregnancy test at screening and should agree to avoid pregnancy through the end of the vaccine phase of the study. Females who are engaging in sexual intercourse must be willing to practice a reliable method of birth control through the end of the vaccine-phase of the study (approximately 6 months). The decision of what is "reliable" is at the discretion of the site investigator.

Exclusion Criteria:

* Presence of any serious illness requiring treatment with systemic medications, excluding treatment for asthma.
* Previous allergic reaction to any vaccines or to constituents of these vaccines (yeast, thimerosal or aluminum)
* Pregnancy
* Current immunomodulator therapy
* Receipt of immunosuppressor therapy (more than 10 mg/day of prednisone or equivalent for \>1 week) in the 6 months preceding entry or anticipated long-term corticosteroid therapy in the above dose and duration. Short term (\< 7 days) steroid use for the treatment of asthma is not an exclusion.
* Receipt of any vaccine within 2 weeks preceding study entry.

Primary outcomes:
measure: Qualitative Seroresponsiveness to Hepatitis B Surface Antigen
timeFrame: Week (Wk) 28 (One month after the second immunization)
measure: Safety and Tolerability of Vaccine Regimens of Recombivax and Twinrix (Number of Participants With >=1 Adverse Event (AE))
timeFrame: Week 12, Week 24, Week 28, Week 76
measure: Safety and Tolerability of Vaccine Regimens of Recombivax and Twinrix: Serious Adverse Events (SAE)(Number of Subjects With >= 1 SAE)
timeFrame: Week 12, Week 24, Week 28, Week 76
Secondary outcomes:
measure: Quantitative Vaccine Response
timeFrame: Week 28
measure: Unadjusted Relationship of Hepatitis B Vaccine Response (Log10 Titer) and Potential Impact Factors Among Subjects Whose Week 28 Antibody Results Are Within Week 28 Visit Window.
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen (Binary); Predictor: STUDY ARM.
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: SITE EFFECT
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: AGE
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: GENDER
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: HISPANIC ETHNICITY
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: RACE
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TANNER STAGE FOR FEMALES
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TANNER STAGE FOR MALES
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: BMI at Baseline
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER SMOKED CIGARETTES
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: SEXUAL IDENTITY
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: AGE AT WHICH SUBJECT FIRST HAD SEX (NOT FORCED)
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME SEX PARTNERS
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME MALE SEX PARTNERS
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME FEMALE SEX PARTNERS
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER DRANK ALCOHOL
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER SMOKED MARIJUANA
timeFrame: Week 28
measure: Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER USED DRUGS NOT PRESCRIBE
timeFrame: Week 28
measure: Immunogenicity to Hep B 18 Months After First Immunization
timeFrame: Week 76
measure: Immunogenicity to Hep A in the Twinrix Arm: One Month Post 2nd Vaccination
timeFrame: Week 28
measure: Immunogenicity to Hep A in Twinrix Arm: Twelve Months Post 2nd Vaccination
timeFrame: Week 76
measure: Immunogenicity to Hep A in Twinrix Arm: Overall Response (1-month or 12-month After 2nd Vaccination)
timeFrame: Week 28 and Week 76
measure: As Treated Analysis - Adequate Antibody Response to Hep B Surface Antigen
timeFrame: Week 28
measure: Assessment of Youth Understanding of Vaccine Trial and Informed Consent
timeFrame: Screening
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Washington
country: United States
facility: Children's Hospital National Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: University of Southern Florida College of Medicine
state: Florida
city: Chicago
country: United States
facility: Ruth M Rothstein CORE Center/ John H Stroger Jr Hospital
state: Illinois
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Memphis
country: United States
facility: St. Jude Childrens Research Hospital
state: Tennessee
city: San Juan
country: Puerto Rico
facility: Unversity of Peurto Rico School of Medicine
Study officials:
affiliation: Duke University
name: Coleen K. Cunningham, MD
role: STUDY_CHAIR
References:
citation: Cunningham CK, Rudy BJ, Xu J, Bethel J, Kapogiannis BG, Ahmad S, Wilson CM, Flynn PM; Adolescent Medicine Trials Network for HIV/AIDS Interventions. Randomized trial to determine safety and immunogenicity of two strategies for hepatitis B vaccination in healthy urban adolescents in the United States. Pediatr Infect Dis J. 2010 Jun;29(6):530-4. doi: 10.1097/INF.0b013e3181d285c7.