Hepatitis BPhase 2NCT00107042
Effectiveness of Two Hepatitis B Vaccines in HIV-negative Youths
A Phase 2 study testing Recombivax and Twinrix in people with Hepatitis B, run by University of North Carolina, Chapel Hill at 11 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 12 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis B
- What is being tested?
- Recombivax and Twinrix
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 123 participants
- Where
- 11 sitesin 2 countries
- Study dates
- Feb 2004to Jul 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States10 sites
University of Maryland
Baltimore, Maryland, 21201
Ruth M Rothstein CORE Center/ John H Stroger Jr Hospital
Chicago, Illinois, 60612
Children's Hospital of Los Angeles
Los Angeles, California, 90027
St. Jude Childrens Research Hospital
Memphis, Tennessee, 38105-2794
Tulane Medical Center
New Orleans, Louisiana, 70112
University of California at San Diego
San Diego, California, 92103
University of California at San Francisco
San Francisco, California, 94118
University of Southern Florida College of Medicine
Tampa, Florida, 33606
Montefiore Medical Center
The Bronx, New York, 10467
Children's Hospital National Medical Center
Washington D.C., District of Columbia, 20010
Puerto Rico1 site
Unversity of Peurto Rico School of Medicine
San Juan, 00936
About this study
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.
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).
Read the 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.
- Conditions
- Hepatitis B
- Being tested
- Recombivax, Twinrix
- Keywords
- Hepatitis B, HIV vaccine trial
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RecombivaxBiological
Participants receive doses of Recombivax at weeks 0 and 24.
TwinrixBiological
Participants receive doses of Twinrix at weeks 0 and 24.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Participants receive doses of Recombivax at weeks 0 and 24. A risk-behavior assessment is administered at week 12 and post-vaccination follow-up visits and bloodwork occur at weeks 28 and 76. Receives: Biological: Recombivax |
| 2 | Experimental | Participants receive doses of Twinrix at weeks 0 and 24. A risk-behavior assessment is administered at week 12 and post-vaccination follow-up visits and bloodwork occur at weeks 28 and 76. Receives: Biological: Twinrix |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week (Wk) 28 (One month after the second immunization)
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.
Measured: Week 12, Week 24, Week 28, Week 76
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.
Measured: Week 12, Week 24, Week 28, Week 76
Secondary outcomes (26)
Quantitative Vaccine Response
The Log10 titer was used as the quantitative vaccine response.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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.
Measured: Week 28
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
Measured: Week 76
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.
Measured: Week 28
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.
Measured: Week 76
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.
Measured: Week 28 and Week 76
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.
Measured: Week 28
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.
Measured: Screening
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2005 (estimated)
- Study startFeb 2004
- Primary completionJul 2008
- Study completionJul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis BStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- 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)
- Responsible party
- Sponsor
- Investigators
- Coleen K. Cunningham, MD, Study chair, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00107042
- Sponsor's protocol ID
- ATN 025
- Status last verified
- Mar 2016
- First submitted
- 4 Apr 2005
- Last updated
- 29 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 20173677
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00107042
- Acronym / sponsor ID
- ATN 025
- Conditions
- Hepatitis B
- Keywords
- Hepatitis B, HIV vaccine trial
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- 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 start
- Feb 2004
- Primary completion
- Jul 2008 (actual)
- Study completion
- Jul 2008 (actual)
- First posted
- 5 Apr 2005 (estimated)
- Results
- Posted 4 Dec 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Biological: RecombivaxParticipants receive doses of Recombivax at weeks 0 and 24. A risk-behavior assessment is administered at week 12 and post-vaccination follow-up visits and bloodwork occur at weeks 28 and 76. |
| 2 | Experimental | Biological: TwinrixParticipants receive doses of Twinrix at weeks 0 and 24. A risk-behavior assessment is administered at week 12 and post-vaccination follow-up visits and bloodwork occur at weeks 28 and 76. |
Who may qualify
- Ages
- 12 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RecombivaxParticipants receive doses of Recombivax at weeks 0 and 24. | Biological | 1 |
| TwinrixParticipants receive doses of Twinrix at weeks 0 and 24. | Biological | 2 |
Primary outcome
Qualitative Seroresponsiveness to Hepatitis B Surface Antigen
Time frame: Week (Wk) 28 (One month after the second immunization)
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.
Safety and Tolerability of Vaccine Regimens of Recombivax and Twinrix (Number of Participants With >=1 Adverse Event (AE))
Time frame: Week 12, Week 24, Week 28, Week 76
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.
Safety and Tolerability of Vaccine Regimens of Recombivax and Twinrix: Serious Adverse Events (SAE)(Number of Subjects With >= 1 SAE)
Time frame: Week 12, Week 24, Week 28, Week 76
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.
26 secondary outcomes
Quantitative Vaccine Response
Time frame: Week 28
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.
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B (Hep B) Surface Antigen (Binary); Predictor: STUDY ARM.
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: SITE EFFECT
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: AGE
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: GENDER
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: HISPANIC ETHNICITY
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: RACE
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TANNER STAGE FOR FEMALES
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TANNER STAGE FOR MALES
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: BMI at Baseline
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER SMOKED CIGARETTES
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: SEXUAL IDENTITY
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: AGE AT WHICH SUBJECT FIRST HAD SEX (NOT FORCED)
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME SEX PARTNERS
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME MALE SEX PARTNERS
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: TOTAL LIFETIME FEMALE SEX PARTNERS
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER DRANK ALCOHOL
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER SMOKED MARIJUANA
Time frame: Week 28
Outcome Measure: Qualitative Vaccine Response to Hepatitis B Surface Antigen (Binary); Predictor: EVER USED DRUGS NOT PRESCRIBE
Time frame: Week 28
Immunogenicity to Hep B 18 Months After First Immunization
Time frame: Week 76
Immunogenicity to Hep A in the Twinrix Arm: One Month Post 2nd Vaccination
Time frame: Week 28
Immunogenicity to Hep A in Twinrix Arm: Twelve Months Post 2nd Vaccination
Time frame: Week 76
Immunogenicity to Hep A in Twinrix Arm: Overall Response (1-month or 12-month After 2nd Vaccination)
Time frame: Week 28 and Week 76
As Treated Analysis - Adequate Antibody Response to Hep B Surface Antigen
Time frame: Week 28
Assessment of Youth Understanding of Vaccine Trial and Informed Consent
Time frame: Screening
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 20173677Cunningham 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.
- Adolescent Trials Network for HIV/AIDS InterventionLink provided by the sponsor.
Related trials for Hepatitis B
Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Coleen K. Cunningham, MD study chair
Duke University
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Recombivax and Twinrix in people with Hepatitis B, run by University of North Carolina, Chapel Hill at 11 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Qualitative Seroresponsiveness to Hepatitis B Surface Antigen (time frame: Week (Wk) 28 (One month after the second immunization)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00107042, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2017.