Comparison of Three Hepatitis B Vaccination Regimens in HIV-Positive Youth

Phase 4

Completed

• Conditions: HIV Infection; Hepatitis B
• Interventions: Biological: Engerix-B 20 mcg; Biological: Engerix-B 40 mcg; Biological: Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg

• Registration Number: NCT00106964
• Lead Sponsor: University of North Carolina, Chapel Hill

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.

Detailed Description

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:

1. standard adult dosing of HBV-only vaccine: Engerix-B 20 mcg at Entry, Week 4 and Week 24

2. increased adult dosing of HBV-only vaccine: Engerix-B 40 mcg at Entry, Week 4 and Week 24

3. 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 Timeline

• Study Start: 2004-01
• Study First Submitted: 2005-04-01
• Study First Submitted QC: 2005-04-01
• Study First Posted: 2005-04-04
• Primary Completion: 2008-01
• Study Completion: 2009-06
• Results First Submitted: 2012-10-26
• Results First Submitted QC: 2013-04-30
• Results First Posted: 2013-06-28
• Status Verified: 2016-02
• Last Update Submitted: 2017-02-27
• Last Update Posted: 2017-03-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 371

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Engerix-B 20 mcg	Standard dose (20 mcg) of Hepatitis B vaccine.
2	Engerix-B 40 mcg	40 mcg of Hepatitis B vaccine
3	Twinrix 720 EIA HAV Ag plus 20 mcg HBsAg	20 mgc of Twinrix

Primary Outcome Measures

Name	Time	Method
Sero-response to Hepatitis B Surface Antigen	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

Name	Time	Method
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - POSSIBLY OR PROBABLY RELATED	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 - ABNORMAL LABORATORY VALUES GRADE 2 OR ABOVE BY INTERVENTION ARM ON STUDY	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.
Sero-Response to Hepatitis B Surface Antigen; Predictor: STUDY ARM	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.
Safety of 3 Hepatitis B Vaccine Regimens in HIV+ Youth - ADVERSE EVENTS BY INTERVENTION ARM ON STUDY - DEFINITELY RELATED	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.
Response Rates in HIV+ Youth Within Each Study Arm by Study Duration	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.

Trial Locations

Locations (11)

Ippmg-Ufrj; 🇧🇷 Rio de Janeiro, Brazil

Tulane Med Center; 🇺🇸 New Orleans, Louisiana, United States

Childrens Hosp of Los Angeles; 🇺🇸 Los Angeles, California, United States

University of California at San Francisco; 🇺🇸 San Fransisco, California, United States

Federal University of Minas Gerais; 🇧🇷 Belo Horizonte, MG, Brazil

Children's Hosp Natinal Med Center; 🇺🇸 Washington, District of Columbia, United States

Instituto de Infectologia Emilio Ribas; 🇧🇷 Sao Paulo, SP, Brazil

Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto/USP; 🇧🇷 Ribeirao Preto, SP, Brazil

Hospital dos Sevidores do Estado; 🇧🇷 Rio de Janeiro, Brazil

Tygerberg Hospital; 🇿🇦 Bellville, Cape Town, South Africa

Harriet Shezi Childrens Clinic Chris Hani Baragwanth Hospital; 🇿🇦 Johannesburg, Gauteng, South Africa