Trial Comparing Two Strategies of Vaccination Against Hepatitis B in HIV-infected Patients Non Responding to Primary Immunization (B-BOOST)

Study Overview
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Brief Summary
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HIV infected patients exposed to Hepatitis B virus are more susceptible to develop a chronic and severe liver disease, with a major risk of cirrhosis and liver cancer. However, immune response to standard Hepatitis B vaccination is decreased in HIV-infected patients, compared to non HIV-infected individuals, and, in case of response, its durability has to be carefully followed up. This study compares the efficacy of two strategies of revaccination in HIV-infected patients who didn't respond to previous hepatitis B vaccination. Failure is defined by two conditions: non response to the primary immunization (2 to 4 single-dose injections received before the screening visit) and failure to a single 20 µg boost before being included in the study.

Detailed Description
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Comparison of 2 revaccination strategies in randomized HIV-infected patients with T CD4 cell count above 200/mm3 Intervention: Arm A: GenHevac-B® 20μg IM at M0, M1, M6 Arm B: GenHevac-B® 40μg IM at M0, M1, M6

Official Title
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Open-label, Randomized, and Multicenter Phase III Clinical Trial Comparing Immunogenicity of Double-dose (40 µg at S0, S4 and S24), Versus Standard Dose Vaccination (20 µg at S0, S4 and S24), Against Hepatitis B Virus in HIV-1-infected Patients Without Any Previous Immune Response After Primary Immunization Plus One Single Boost

Conditions
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Hepatitis B, HIV Infection

Intervention / Treatment
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* Biological: GenHevac-B
* Biological: GenHevac-B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infection T CD4 cell count number above 200 /mm3 History of 2 to 4 injections of Hepatitis B vaccine, at any time in the past No history of Hepatitis B vaccination with a double-dose schedule No response to Hepatitis B vaccination: serology Hepatitis B negative (AgHBs, AbHBs and AbHBc negative) the previous twelve months and at the screening visit AbHBs titers below 10 IU/ml four weeks after the boost of Genhevac-B® 20μg preceding the randomization unchanged ARV treatment for the last 2 months for patients who are receiving ARV at the screening visit Undetectable HIV RNA for the last 6 months and on-going ARV for any patients with T CD4 cell level below 350/mm3 HIV-1 plasma load below 100 000 copies per ml for patients without ARV Negative pregnancy test at the screening visit, and immediately before the Genhevac-B® 20 µg boost injection preceding the randomization Exclusion Criteria: Acute cytolysis in the last 3 months with transaminases equal or above 5 times the upper limit of normal for HIV-HCV coinfected patients, or transaminases equal or above 2 times the upper limit of normal for non coinfected patients Any vaccine received during the month preceding the inclusion History of hypersensitivity to any component of GenHevac-B acute opportunistic infection treated the month before the screening visit Severe and acute pyretic infection or unexplained fever the week before inclusion Hemopathy or solid-organ cancer Prothrombin factor equal or below 50% and/or platelets equal or below 50 000 per mm3 Immunosuppressive treatment or general corticotherapy (equal or above 0,5 mg per kg per day during at least 7 days) in the last 6 months before the screening visit Immunomodulating treatment (interferon, interleukine-2,…) in the last 6 months before the screening visit Splenectomy Decompensated cirrhosis (Child Pugh B or C) Renal failure (creatinine clearance below 50 ml/mn) Other severe immunocompromised condition not related to HIV infection (solid-organ transplantation, chemotherapy in the last 6 months,….) Any participation to another clinical trial plan until Week 28

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>GenHevac-B 20 microgram intramuscular use at M0, M1 and M6 | Biological: GenHevac-B<br>* 1 intramuscular injection of Genhevac-B® 20μg on day zero, month 1,and month 6<br>* Other names: Sanofi Pasteur MSD;|
| Experimental: B<br>GenHevac-B 40 microgram intramuscular use at M0, M1 and M6 | Biological: GenHevac-B<br>* 2 intramuscular injections of Genhevac-B® 20μg on day zero, month 1,and month 6<br>* Other names: Sanofi Pasteur MSD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of HIV-infected patients who seroconvert one month after the last vaccination. Seroconversion is defined as anti-HBs titers equal or above 10 mUI per ml |  | one month after the last vaccination (week 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| According to the vaccine strategy (single-dose or double-dose), comparison of AbHBs titers, permanence of humoral response, intensity of clinical and biological events, and predicting factors related to seroconversion |  | one month after the last injection ( week 28) and month 18 | 
| immunological substudy: to understand genetic link between some alleles of HLA-DR and non-response to immunization |  | at D0 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B vaccination, GenHevac-B Pasteur, HIV infection