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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
| National Institute of Mental Health (NIMH) | NIH |
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | NIH |
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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | Standard dose (20 mcg) of Hepatitis B vaccine. |
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| 2 | Active Comparator | 40 mcg of Hepatitis B vaccine |
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| 3 | Active Comparator | 20 mgc of Twinrix |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Engerix-B 20 mcg | Biological | A single dose of 1 mL (20 mcg/mL) will be administered in the deltoid muscle at Entry, Weeks 4 and 24. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Sero-response to Hepatitis B Surface Antigen | 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. | Week 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - POSSIBLY OR PROBABLY RELATED | 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. |
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Inclusion Criteria:
Exclusion Criteria:
Presence of any known grade >= 3 clinical or laboratory toxicity at the time of pre-entry per toxicity tables.
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| Name | Affiliation | Role |
|---|---|---|
| Patricia Flynn, MD | St. Jude Children's Research Hospital | Study Chair |
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Childrens Hosp of Los Angeles | Los Angeles | California | 90054 | United States | ||
| University of California at San Francisco |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21350366 | Result | 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. |
| Label | URL |
|---|---|
| Website for the Adolescent Trials Network for HIV/AIDS Interventions | View source |
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Subjects were randomized into one of three arms using blocks of six and stratified by absolute CD4 count (less than 500 and 500 cells/mL or greater) and previous hepatitis B virus (HBV) vaccination (0,1). The randomization was restricted so that the percentage of subjects with CD4 count < = 200 cells/mL would not exceed 15% of subjects on any arm.
This is a multi-site study. Accrual was open between April 2006 and January 2008. Participants were enrolled in the United States, South Africa, Brazil, and the Bahamas.
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| ID | Title | Description |
|---|---|---|
| FG000 | 1: Engerix 20 mcg | Standard dose (20 mcg) of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. |
| FG001 | 2: Engerix 40 mcg | 40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Engerix-B 40 mcg | Biological | A single dose of 2 mL (20 mcg/mL) will be administered in the deltoid muscle at Entry, Week 4 and 24. |
|
| Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg | Biological | Arm 3: 720 EIA HAV Ag, 20 mcg HBsAg/ml: A single dose of 1 mL will be administered in the deltoid muscle. |
|
| Baseline through Week 72 |
| Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - DEFINITELY RELATED | 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. | Baseline through Week 72 |
| Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ABNORMAL LABORATORY VALUES GRADE 2 OR ABOVE BY INTERVENTION ARM ON STUDY | 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. | Baseline through Week 72 |
| Response Rates in HIV+ Youth Within Each Study Arm by Study Duration | 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. | Entry through Week 72 |
| Sero-Response to Hepatitis B Surface Antigen; Predictor: STUDY ARM | 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. | Week 28 |
| 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 | Principal Investigator |
| San Francisco |
| California |
| 94118 |
| United States |
| Children's Hosp Natinal Med Center | Washington D.C. | District of Columbia | 20010 | United States |
| Tulane Med Center | New Orleans | Louisiana | 70112 | United States |
| Federal University of Minas Gerais | Belo Horizonte | Minas Gerais | 30130-100 | Brazil |
| Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto/USP | Ribeirão Preto | São Paulo | 14049-900 | Brazil |
| Instituto de Infectologia Emilio Ribas | São Paulo | São Paulo | 01246-900 | Brazil |
| Hospital dos Sevidores do Estado | Rio de Janeiro | 20221-903 | Brazil |
| Ippmg-Ufrj | Rio de Janeiro | 21941590 | Brazil |
| Tygerberg Hospital | Bellville | Cape Town | 7505 | South Africa |
| Harriet Shezi Childrens Clinic Chris Hani Baragwanth Hospital | Johannesburg | Gauteng | 2013 | South Africa |
| FG002 | 3: Twinrix 20 mcg | 20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 1: Engerix 20 mcg | Standard dose (20 mcg) of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. |
| BG001 | 2: Engerix 40 mcg | 40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. |
| BG002 | 3: Twinrix 20 mcg | 20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Number | participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Sero-response to Hepatitis B Surface Antigen | 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. | Participants who completed a Week 28 visit with a Hepatitis B serology result were included in this analysis. | Posted | Number | percentage of participants who resonded | Week 28 |
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| Secondary | Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - POSSIBLY OR PROBABLY RELATED | 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. | All enrolled participants were included in this analysis of all AEs that were possibly or probably related to study drug. There were no AEs above Grade 3 considered to be possibly or probably related to study drug. | Posted | Number | Events | Baseline through Week 72 |
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| Secondary | Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - DEFINITELY RELATED | 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. | All enrolled participants were included in this analysis of AEs that were definitely related to study drug. There were no AEs above Grade 2 considered to be definitely related to study drug. | Posted | Number | event | Baseline through Week 72 |
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| Secondary | Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ABNORMAL LABORATORY VALUES GRADE 2 OR ABOVE BY INTERVENTION ARM ON STUDY | 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. | All enrolled participants were included in this analysis. The following no. of participants experienced at least one Grade 2 or higher abnormal labs by study arm. | Posted | Number | Events | Baseline through Week 72 | Events | Events |
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| Secondary | Response Rates in HIV+ Youth Within Each Study Arm by Study Duration | 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. | Population analyzed were those who had an antibody titer measured at Week 28. | Posted | Number | percentage of participants who responded | Entry through Week 72 |
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| Secondary | Sero-Response to Hepatitis B Surface Antigen; Predictor: STUDY ARM | 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. | All participants who had a Week 28 Hepatitis B serology result | Posted | Number | percentage of participants who responded | Week 28 |
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Data were collected over a three year time period.
There were no Serious Adverse Events (SAE) to report
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1: Engerix 20 mcg | Standard dose (20 mcg) of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. | 0 | 118 | 28 | 118 | ||
| EG001 | 2: Engerix 40 mcg | 40 mcg of Hepatitis B vaccine. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. | 0 | 126 | 25 | 126 | ||
| EG002 | 3. Twinrix 20 mcg | 20 mcg of Twinrix. Dose #1 at Entry; Dose #2 at Week 4; Dose #3 at Week 24. | 0 | 127 | 25 | 127 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| General Disorders and Administration Site Conditions | General disorders | Systematic Assessment |
| ||
| Nervous System Disorders | Nervous system disorders | Systematic Assessment |
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| Gastrointestinal Disorders | Gastrointestinal disorders | Systematic Assessment |
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| Investigations | Investigations | Systematic Assessment |
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| Blood and lymphatic System Disorders | Blood and lymphatic system disorders | Systematic Assessment |
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| Infecions and Infestations | Infections and infestations | Systematic Assessment |
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The Adolescent Medicine Trials Network (ATN) for HIV/AIDS Interventions Publication Policy outlines procedures for the development and review of abstracts, publications and presentations. The Adolescent Medicine Leadership Group (AMLG) retains custody of and primary rights to the data. Use of data must be approved by protocol team and AMLG.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Bob Harris | Westat | 301-251-1500 | bobharris@westat.com |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D006509 | Hepatitis B |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D018347 | Hepadnaviridae Infections |
| D004266 | DNA Virus Infections |
| D006525 | Hepatitis, Viral, Human |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C075654 | Engerix-B |
| D006514 | Hepatitis B Surface Antigens |
| ID | Term |
|---|---|
| D006511 | Hepatitis B Antigens |
| D018963 | Hepatitis Antigens |
| D000956 | Antigens, Viral |
| D014764 | Viral Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000941 | Antigens |
| D001685 | Biological Factors |
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| 14-15 years |
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| 16-19 years |
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| >20 years |
|
| Male |
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| South Africa |
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| Brazil |
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| Bahamas |
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| Superiority or Other |
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| Units | Counts |
|---|---|
| Participants |
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| Participants |
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