Clinical trial NCT00670839: Trial Comparing Two Strategies of Vaccination Against Hepatitis B in HIV-infected Patients Non Responding to Primary Immunization (B-BOOST)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis B
HIV Infection
Keywords: Hepatitis B vaccination
GenHevac-B Pasteur
HIV infection
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: MCM Vaccines B.V.
First posted: 2008-05-02
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: Comparison of 2 revaccination strategies in randomized HIV-infected patients with T CD4 cell count above 200/mm3

Intervention:

1. Arm A: GenHevac-B® 20μg IM at M0, M1, M6
2. Arm B: GenHevac-B® 40μg IM at M0, M1, M6

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: one month after the last vaccination (week 28)
Secondary outcomes:
measure: 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
timeFrame: one month after the last injection ( week 28) and month 18
measure: immunological substudy: to understand genetic link between some alleles of HLA-DR and non-response to immunization
timeFrame: at D0
Other outcomes:
Locations:
city: Strasbourg
country: France
facility: Centre de Soins de l'Infection par le VIH NHC, Hôpitaux Universitaires Strasbourg, 1 place de l'hôpital
Study officials:
affiliation: Hôpital civil, Strasbourg, France
name: David Rey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inserm U707 Paris France
name: Fabrice Carrat, MD
role: STUDY_CHAIR
References:
citation: Rey D, Piroth L, Wendling MJ, Miailhes P, Michel ML, Dufour C, Haour G, Sogni P, Rohel A, Ajana F, Billaud E, Molina JM, Launay O, Carrat F; ANRS HB04 B-BOOST study group. Safety and immunogenicity of double-dose versus standard-dose hepatitis B revaccination in non-responding adults with HIV-1 (ANRS HB04 B-BOOST): a multicentre, open-label, randomised controlled trial. Lancet Infect Dis. 2015 Nov;15(11):1283-91. doi: 10.1016/S1473-3099(15)00220-0. Epub 2015 Aug 6.