Effectiveness of Two Hepatitis B Vaccines in HIV-negative Youths

Hepatitis B Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00107042
• Other study ID #: ATN 025
• Status: Completed
• Phase: Phase 2
• First received: April 4, 2005
• Last updated: February 12, 2015
• Start date: February 2004
• Est. completion date: July 2008

Study information

• Verified date: December 2014
• Source: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 12 Years to 17 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B

Intervention

Biological:
• Recombivax
Participants receive doses of Recombivax at weeks 0 and 24.
• Twinrix
Participants receive doses of Twinrix at weeks 0 and 24.

Locations

Country	Name	City	State
Puerto Rico	Unversity of Peurto Rico School of Medicine	San Juan
United States	University of Maryland	Baltimore	Maryland
United States	Montefiore Medical Center	Bronx	New York
United States	Ruth M Rothstein CORE Center/ John H Stroger Jr Hospital	Chicago	Illinois
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	St. Jude Childrens Research Hospital	Memphis	Tennessee
United States	Tulane Medical Center	New Orleans	Louisiana
United States	University of California at San Diego	San Diego	California
United States	University of California at San Francisco	San Francisco	California
United States	University of Southern Florida College of Medicine	Tampa	Florida
United States	Children's Hospital National Medical Center	Washington	District of Columbia

Sponsors (4)

Lead Sponsor	Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	National Institute of Mental Health (NIMH), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Drug Abuse (NIDA)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Qualitative Seroresponsiveness to Hepatitis B Surface Antigen	Seroresponsiveness to Hepatitis B Surface Antigen is defined as follows: Responder: serum antibody level is greater than or equal to 10 mIU/mL. Non-responder: serum antibody level is less than 10 mIU/mL.	Week (Wk) 28 (One month after the second immunization)	No
Primary	Safety and Tolerability of Vaccine Regimens of Recombivax and Twinrix (Number of Participants With >=1 Adverse Event (AE))	Frequency Distribution of AEs by Study Arm and Preferred Term. The safety and tolerability of each vaccine was assessed by measuring reactogenicity. The reactions were coded as "Any" vs. "None". In summarizing the distribution of AEs, the number of subjects with at least one event by preferred term and study arm were reported.	Week 12, Week 24, Week 28, Week 76	Yes
Primary	Safety and Tolerability of Vaccine Regimens of Recombivax and Twinrix: Serious Adverse Events (SAE)(Number of Subjects With >= 1 SAE)	Frequency Distribution of SAE by Study Arm and Preferred Term. The safety and tolerability of each vaccine was assessed by measuring reactogenicity. The reactions were coded as "Any" vs. "None". The number of participants with at least one SAE is reported.	Week 12, Week 24, Week 28, Week 76	Yes
Secondary	Quantitative Vaccine Response	The Log10 titer was used as the quantitative vaccine response.	Week 28	No
Secondary	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.	The Log10 titer at Week 28 was used as the quantitative continuous vaccine response.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen (Binary); Predictor: STUDY ARM.	Qualitative Vaccine Response to Hepatitis B Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Study arm was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: SITE EFFECT	Qualitative Vaccine Response to Hepatitis B Surface Antigen is defined as a "Responder" if serum antibody level is >= 10 mIU/mL and a "Non- Responder" if a serum a'body level is < 10 mIU/mL. Site effect was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: AGE	Qualitative Vaccine Response to Hepatitis B (Hep B)Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Age was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: GENDER	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum a'body level is < 10 mIU/mL. Gender was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: HISPANIC ETHNICITY	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Hispanic ethnicity was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: RACE	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Race was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TANNER STAGE FOR FEMALES	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Tanner stage by gender was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TANNER STAGE FOR MALES	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Tanner stage by gender was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: BMI at Baseline	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. BMI at baseline was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER SMOKED CIGARETTES	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Whether participants ever smoked cigarettes was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: SEXUAL IDENTITY	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Sexual identity was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: AGE AT WHICH SUBJECT FIRST HAD SEX (NOT FORCED)	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Age of participants' first unforced sexual encounter was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME SEX PARTNERS	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Total number of lifetime sex partners was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME MALE SEX PARTNERS	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Total number of lifetime male sex partners was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME FEMALE SEX PARTNERS	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Total number of lifetime female sex partners was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER DRANK ALCOHOL	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Whether participants ever drank alcohol was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER SMOKED MARIJUANA	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Whether participants ever smoked marijuana was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER USED DRUGS NOT PRESCRIBE	Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen is defined as a "Responder" if serum a'body level is >= 10 mIU/mL and a "Non- Responder" if a serum antibody level is < 10 mIU/mL. Whether participants ever used drugs not prescribed was analyzed as a potential impact factor and was measured and examined for the association with both the presence of adequate response as well as the quantitative titer one month post 2 vaccine doses.	Week 28	No
Secondary	Immunogenicity to Hep B 18 Months After First Immunization	Persistence of protective antibody response was measured by presence or absence of 10 mIU/ml HepB surface antibody and geometric mean titer of the same antibody at Week 76	Week 76	No
Secondary	Immunogenicity to Hep A in the Twinrix Arm: One Month Post 2nd Vaccination	Hepatitis A antibody response in those subjects in the combined vaccine arm (Twinrix) at 1 month after the 2nd vaccination. Immunogenicity to Hepatitis is given as a positive or negative response. If the Hepatitis A serology was reactive, then the participant was considered to have a positive response; if the Hepatitis A serology was non-reactive, then the participant was considered to have a negative response.	Week 28	No
Secondary	Immunogenicity to Hep A in Twinrix Arm: Twelve Months Post 2nd Vaccination	Hepatitis A antibody response in those subjects in the combined vaccine arm (Twinrix) at 12 months after the 2nd vaccination. Immunogenicity to Hepatitis is given as a positive or negative response.	Week 76	No
Secondary	Immunogenicity to Hep A in Twinrix Arm: Overall Response (1-month or 12-month After 2nd Vaccination)	Hepatitis A antibody response in those subjects in the combined vaccine arm (Twinrix) at two time points: 1 and 12 months after the 2nd vaccination. Immunogenicity to Hepatitis is given as a positive or negative response.	Week 28 and Week 76	No
Secondary	As Treated Analysis - Adequate Antibody Response to Hep B Surface Antigen	The subject was considered seroresponsive to Hepatitis B Surface Antigen if the serum antibody level was greater than or equal to 10 mIU/mL. Those who received only a single vaccination, whose second vaccination was outside of the specified time window, or other cases of protocol violations were excluded from the analysis.	Week 28	No
Secondary	Assessment of Youth Understanding of Vaccine Trial and Informed Consent	Assessment of understanding was measured by a questionnaire containing six questions. The summary score is the sum of correct answers from six questions.	Screening	No

External Links

•   Adolescent Trials Network for HIV/AIDS Intervention