Comparison of Three Hepatitis B Vaccination Regimens in HIV-Positive Youth
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| ClinicalTrials.gov Identifier: NCT00106964 |
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Recruitment Status :
Completed
First Posted : April 4, 2005
Results First Posted : June 28, 2013
Last Update Posted : March 29, 2017
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Sponsor:
University of North Carolina, Chapel Hill
Collaborators:
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HIV Infection Hepatitis B | Biological: Engerix-B 20 mcg Biological: Engerix-B 40 mcg Biological: Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg | Phase 4 |
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:
- standard adult dosing of HBV-only vaccine: Engerix-B 20 mcg at Entry, Week 4 and Week 24
- increased adult dosing of HBV-only vaccine: Engerix-B 40 mcg at Entry, Week 4 and Week 24
- 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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 371 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Prevention |
| Official Title: | A Randomized, Open-Label Trial of Three Hepatitis B Vaccination Schemas in HIV-Positive Youth |
| Study Start Date : | January 2004 |
| Actual Primary Completion Date : | January 2008 |
| Actual Study Completion Date : | June 2009 |
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| Arm | Intervention/treatment |
|---|---|
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Active Comparator: 1
Standard dose (20 mcg) of Hepatitis B vaccine.
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Biological: Engerix-B 20 mcg
A single dose of 1 mL (20 mcg/mL) will be administered in the deltoid muscle at Entry, Weeks 4 and 24. |
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Active Comparator: 2
40 mcg of Hepatitis B vaccine
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Biological: Engerix-B 40 mcg
A single dose of 2 mL (20 mcg/mL) will be administered in the deltoid muscle at Entry, Week 4 and 24. |
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Active Comparator: 3
20 mgc of Twinrix
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Biological: Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg
Arm 3: 720 EIA HAV Ag, 20 mcg HBsAg/ml: A single dose of 1 mL will be administered in the deltoid muscle. |
Primary Outcome Measures :
- Sero-response to Hepatitis B Surface Antigen [ Time Frame: Week 28 ]The primary outcome, percentage positive sero-response, was compared between Arm 1 and each of the two alternative strategy arms (Arm 2 and Arm 3) and measured 4 weeks after the third vaccination at Week 28. Response is defined as greater than or equal to 10 IU/mL of serum being present; non-response is defined as less than 10 IU/mL.
Secondary Outcome Measures :
- Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - POSSIBLY OR PROBABLY RELATED [ Time Frame: Baseline through Week 72 ]The number of adverse events (AE) was described by study arm. The proportion of subjects with clinical adverse events in Arms 1 and each of the two alternative strategy arms (Arm 2 and Arm 3) were compared to assess whether or not there is a difference in patients with any grade toxicity.
- Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - DEFINITELY RELATED [ Time Frame: Baseline through Week 72 ]The number of AEs was described by study arm. The proportion of subjects with clinical AEs in Arms 1 and each of the two alternative strategy arms (Arm 2 and Arm 3)were compared to assess whether or not there is a difference in subjects with any grade toxicity.
- Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ABNORMAL LABORATORY VALUES GRADE 2 OR ABOVE BY INTERVENTION ARM ON STUDY [ Time Frame: Baseline through Week 72 ]The number of adverse events and subjects with the events were described by study arm. The proportion of subjects with abnormal labs in Arms 1 and each of the two alternative strategy arms (Arm 2 and Arm 3) were compared to assess whether or not there is a difference in subjects with grade 3 or 4 toxicity. The laboratory events included are AEs classified as probably, possibly, or definitely related to study drug as classified by the Site Investigator.
- Response Rates in HIV+ Youth Within Each Study Arm by Study Duration [ Time Frame: Entry through Week 72 ]Within each arm, the duration of response in HIV-infected youth was analyzed for all subjects who were responders at 28 weeks. The possible values for response duration could be 20 weeks or less (responder at 28 weeks but not at 48 weeks), 20 to 44 weeks (responder at 28 and 48 weeks but not at 72 weeks), or greater than 44 weeks (responder at 28, 48, and 72 weeks). A response of greater than 20 weeks includes those who responded after 20 weeks, but whose exact response duration was unknown.
- Sero-Response to Hepatitis B Surface Antigen; Predictor: STUDY ARM [ Time Frame: Week 28 ]Response rate associated with the participant's study arm, baseline CD4 count, and interaction term that reflects how subjects in Arm 2 responded differently depending on their CD4 count. Response is defined as greater than or equal to 10 IU/mL of serum being present; non-response is defined as less than 10 IU/mL.
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| Ages Eligible for Study: | 12 Years to 24 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00106964
Locations
| United States, California | |
| Childrens Hosp of Los Angeles | |
| Los Angeles, California, United States, 90054 | |
| University of California at San Francisco | |
| San Fransisco, California, United States, 94118 | |
| United States, District of Columbia | |
| Children's Hosp Natinal Med Center | |
| Washington, District of Columbia, United States, 20010 | |
| United States, Louisiana | |
| Tulane Med Center | |
| New Orleans, Louisiana, United States, 70112 | |
| Brazil | |
| Federal University of Minas Gerais | |
| Belo Horizonte, MG, Brazil, 30130-100 | |
| Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto/USP | |
| Ribeirao Preto, SP, Brazil, 14049-900 | |
| Instituto de Infectologia Emilio Ribas | |
| Sao Paulo, SP, Brazil, 01246-900 | |
| Hospital dos Sevidores do Estado | |
| Rio de Janeiro, Brazil, 20221-903 | |
| Ippmg-Ufrj | |
| Rio de Janeiro, Brazil, 21941590 | |
| South Africa | |
| Tygerberg Hospital | |
| Bellville, Cape Town, South Africa, 7505 | |
| Harriet Shezi Childrens Clinic Chris Hani Baragwanth Hospital | |
| Johannesburg, Gauteng, South Africa, 2013 | |
Sponsors and Collaborators
University of North Carolina, Chapel Hill
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
| Study Chair: | Patricia Flynn, MD | St. Jude Children's Research Hospital | |
| Principal Investigator: | Patricia Emmanuel, MD | University of South Florida, Peds. Div. of Infectious Disease | |
| Principal Investigator: | Diane M. Straub, MD | University of South Florida, Peds. Div. of Infectious Disease | |
| Principal Investigator: | Jorge Lujuan-Ziberman, MD | University of South Florida, Peds. Div. of Infectious Disease | |
| Principal Investigator: | Lawrence D'Angelo, MD | Children's National Medical Center, Div. of Aldol & Young Adult Medicine | |
| Principal Investigator: | Carleen Townsend-Akpan, CPNP | Children's National Medical Center, Div. of Aldol & Young Adult Medicine | |
| Principal Investigator: | Jaime Martinez, MD | John H. Stroger Jr. Hospital | |
| Principal Investigator: | Lisa Henry- Reid, MD | John H. Stroger Jr. Hospital | |
| Principal Investigator: | Irma Febo, MD | University Pediatric Hospital | |
| Principal Investigator: | LLeana Blasini, MD | University Pediatric Hospital | |
| Principal Investigator: | Donna Futterman, MD | Montefiore Medical Center | |
| Principal Investigator: | Marina Catallozzi, MD | Montifiore Medical Center | |
| Principal Investigator: | Linda Levin, MD | Icahn School of Medicine at Mount Sinai | |
| Principal Investigator: | Barbara Moscicki, MD | Univ. of California at San Franciso | |
| Principal Investigator: | Coco Auerswald, MD | Univ. of California at San Franciso | |
| Principal Investigator: | Sue Ellen Abdalian, MD | Tulane Medical Center | |
| Principal Investigator: | Ligia Peralta, MD | University of Maryland | |
| Principal Investigator: | Lawrence Friedman, MD | University of Miami | |
| Principal Investigator: | Ana Puga, MD | Children's Diagnostic & Treatment Center | |
| Principal Investigator: | Stephen Spector, MD | University of California, San Diego | |
| Principal Investigator: | Rolando M Viani, MD | University of California, San Diego |
Additional Information:
Publications of Results:
| Responsible Party: | University of North Carolina, Chapel Hill |
| ClinicalTrials.gov Identifier: | NCT00106964 History of Changes |
| Other Study ID Numbers: |
ATN 024 |
| First Posted: | April 4, 2005 Key Record Dates |
| Results First Posted: | June 28, 2013 |
| Last Update Posted: | March 29, 2017 |
| Last Verified: | February 2016 |
Keywords provided by University of North Carolina, Chapel Hill:
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Hepatitis B vaccines HIV-infected adolescents Hepatitis B infection (negative) |
Additional relevant MeSH terms:
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Hepatitis Hepatitis A HIV Infections Hepatitis B Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections |
Lentivirus Infections Retroviridae Infections Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Hepadnaviridae Infections DNA Virus Infections Vaccines Immunologic Factors Physiological Effects of Drugs |