Trial Comparing Three Strategies of Vaccination Against the Virus of Hepatitis B in HIV Infected Patients (VIHVAC-B)

• ClinicalTrials.gov Identifier: NCT00480792
• Recruitment Status: Completed
• First Posted: May 31, 2007
• Last Update Posted: July 23, 2013
• Sponsor: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Collaborator: MCM Vaccines B.V.
• Information provided by (Responsible Party): French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Tracking Information

• First Submitted Date: May 30, 2007
• First Posted Date: May 31, 2007
• Last Update Posted Date: July 23, 2013
• Study Start Date: June 2007
• Actual Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 30, 2007): HIV-infected patients who seroconvert in the first two months after the last vaccination. Seroconversion is defined as antibodies AbHBs titers equal or above 10 mUI per ml. [ Time Frame: two months after the last injection;week 28, month 18, month 30 and month 42 ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: May 30, 2007): According to the vaccine administration (IM or ID) comparison of AbHBs titers,permanence of the humoral response,intensity of clinical and biological events and predicting factors related to seroconversion [ Time Frame: two months after the last injection; week 28, month 18, month 30 and month 42 ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial Comparing Three Strategies of Vaccination Against the Virus of Hepatitis B in HIV Infected Patients
• Official Title: Open-label, Randomized, and Multicentric Phase III Clinical Trial Comparing Three Strategies of Vaccination Against the Virus of Hepatitis B in HIV-1-infected Patients With CD4-positive T-lymphocytes Counts Above 200 permm3 ANRS HB 03 VIHVAC-B

Brief Summary

In HIV infected patients, individuals exposed to the virus of Hepatitis B are more susceptible to develop a chronic and severe liver disease with a major risk of cirrhosis and liver cancer.

However, the existing protocol of vaccination against Hepatitis B is less efficient in HIV-infected patients than in non HIV-infected-patients, and, in case of response, its longevity has to be followed up carefully. This study compares the efficacy of the standard protocol vaccination with GenHevac-B and 2 other protocols, a double-dose of GenHevac-B and a set of intradermal injections of Genhevac-B, in HIV-infected patients with lymphocytes T CD4 level above 200 permm3.

Detailed Description

Comparison of 3 vaccination strategy against Hepatitis B in patients with HIV infection T CD4 above 200 per mm3

Intervention:

1. Arm A: GenHevac-B 20 microgramme Intramuscular use at M0, M1, M6
2. Arm B: GenHevac-B 40 microgramme Intramuscular use at M0, M1, M2, M6
3. Arm C: GenHevac-B 4 microgramme Intradermal use at M0, M1, M2, M6

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: HIV Infections

Intervention

• Biological: GenHevac B Pasteur
  Intra-muscular injection 20 microgramme Intramuscular use at M0, M1, M6
  Other Name: Sanofi Pasteur MSD
• Biological: GenHevac B Pasteur
  Intra-muscular injection 40 microgramme intramuscular use at M0, M1,M2, M6
  Other Name: Sanofi Pasteur MSD
• Biological: GenHevac B Pasteur
  GenHevac-B 4 microgramme Intradermal use at M0, M1, M2, M6
  Other Name: Sanofi Pasteur MSD

Study Arms

• Active Comparator: A
  GenHevac-B 20 microgramme Intramuscular use at M0, M1, M6
  Intervention: Biological: GenHevac B Pasteur
• Experimental: B
  GenHevac-B 40 microgramme Intramuscular use at M0, M1, M2, M6
  Intervention: Biological: GenHevac B Pasteur
• Experimental: C
  GenHevac-B 4 microgramme Intradermal use at M0, M1, M2, M6
  Intervention: Biological: GenHevac B Pasteur

Publications *

• Launay O, Rosenberg AR, Rey D, Pouget N, Michel ML, Reynes J, Neau D, Raffi F, Piroth L, Carrat F; ANRS HB03 VIHVAC-B (Trial Comparing 3 Strategies of Vaccination Against the Virus of Hepatitis B in HIV-Infected Patients) Group. Long-term Immune Response to Hepatitis B Virus Vaccination Regimens in Adults With Human Immunodeficiency Virus 1: Secondary Analysis of a Randomized Clinical Trial. JAMA Intern Med. 2016 May 1;176(5):603-10. doi: 10.1001/jamainternmed.2016.0741.
• Launay O, van der Vliet D, Rosenberg AR, Michel ML, Piroth L, Rey D, Colin de Verdière N, Slama L, Martin K, Lortholary O, Carrat F; ANRS HB03 VIHVAC-B Trial. Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low doses vs standard hepatitis B vaccine regimen in adults with HIV-1: a randomized controlled trial. JAMA. 2011 Apr 13;305(14):1432-40. doi: 10.1001/jama.2011.351.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 22, 2013): 437
• Original Estimated Enrollment (submitted: May 30, 2007): 420
• Actual Study Completion Date: September 2012
• Actual Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Age Eligible for Study: 18 years - NA, Genders Eligible for Study: Both

Criteria

Inclusion criteria:

• HIV infection
• T CD4 count cell level above 200 per mm3
• Serology Hepatitis B negative (AgHBs, AbHBs and AbHBc negative)
• unchanged ARV for the last 3 months for patients who are receiving ARV at the screening visit
• Undetectable for the last 6 months with ARV for any patient with T CD4 level below 350 per mm3
• Pregnancy test negative at the screening and inclusion visits

Exclusion Criteria:

• Any injection of the vaccine against Hepatitis B in the medical history
• Acute cytolysis in the last 3 months with transaminases equal or above 5 times the upper normal range for HIV-HCV coinfected patients, or transaminases equal or above 2 times the upper normal for non coinfected patients
• Any vaccine received one month before the inclusion
• History of intolerance to any component of GenHevac-B
• Evolutive opportunistic infection treated the month before the screening visit
• Severe and acute pyretic infection or unexplained fever the week before inclusion
• Evolutive hemopathy or solid-organ cancer
• Prothrombin factor equal or below 50 percent 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 above 7 days) in the last 6 months before the screening visit
• Previous Immunomodulating treatment (interferon, interleukin-2,etc) or plan in the next 6 months
• Splenectomy
• Decompensated cirrhosis (Child Pugh B or C)
• Kidney deficient function (creatinine clearance below 50 ml per mn)
• Other 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00480792
• Other Study ID Numbers: 2006-003940-50; ANRS HB 03 VIHVAC-B
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Study Sponsor: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Collaborators: MCM Vaccines B.V.

Investigators

• Principal Investigator: Odile Launay, MD; CIC de vaccinologie Cochin-Pasteur 27, rue du Fb Saint Jacques 75014 Paris Fr
• Study Chair: Fabrice Carrat, MD; Inserm U707 27, rue de Chaligny 75571 Paris cedex 12 Fr

• PRS Account: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Verification Date: July 2013