Lamivudine and Therapeutic Vaccine Evaluation in Senegalese Patients With Chronic Hepatitis B Infection (ANRS 12100 HEPADAK-2)

This study has been terminated.
(poor patient recrutment)
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:
NCT00120796
First received: July 12, 2005
Last updated: March 28, 2008
Last verified: March 2008
  Purpose

Chronic hepatitis B infection is a major public health issue in Senegal. The study will compare the efficacy of the treatment strategy combining Lamivudine and therapeutic vaccine (12 intra-muscular injections over a 6-month period) to a treatment with Lamivudine alone on the control of viral replication in patients with a replicative hepatitis B virus (HBV) infection and an increase in hepatic enzymes.


Condition Intervention Phase
Hepatitis B
Drug: Lamivudine
Biological: Recombinant hepatitis B surface antigen
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Lamivudine and Therapeutic Vaccine Evaluation in Senegalese Patients With Chronic Hepatitis B Infection

Resource links provided by NLM:


Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:
  • undetectability of HBV DNA blood level [ Time Frame: 12 months after treatment initiation (6 months after the end of the treatment) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • HBV DNA blood levels [ Time Frame: 3, 6, 9 and 12 months after the end of the treatment ] [ Designated as safety issue: No ]
  • Transaminases blood level [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Lamivudine treatment compliance [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Feasibility of the vaccine injections schedule [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • AgHBe seroconversion (in positive patients) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • AgHBs negativation [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 210
Study Start Date: August 2005
Estimated Study Completion Date: July 2008
Estimated Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Lamivudine alone
Drug: Lamivudine
Experimental: 2
Lamivudine + Vaccine
Drug: Lamivudine Biological: Recombinant hepatitis B surface antigen

Detailed Description:

Hepatitis B infection with a prevalence higher than 15% of positive Ag HBs subjects is a major public health issue in Senegal. A program of treatment of patients presenting with hepatic disease is currently ongoing through a network of specialists in GI tract and liver diseases. Hepatitis B is a real threat in the Senegalese population as showed in a pilot study (HEPADAK I) performed at the Dakar Hospital Principal (DHP) in Dakar among 100 blood donors and 50 patients with liver disease. This study allowed us to better characterize the strains at the molecular level. The aim of the project is to assess a pragmatic treatment strategy which can be applied to Senegal or other developing countries for patients requiring treatment. A recent Japanese study performed in Ag HBe positive patients reported the interest of the combination of Lamivudine (LAM) and a therapeutic vaccine with the negativation of viral load in 100% of patients after one year of treatment. It is important to show that such a treatment with 12 intra-muscular injections of the vaccine over a 6-month period is feasible in Africa and to assess the results of such a treatment in the Senegalese population, which is mainly AgHBe negative.

The study HEPADAK 2 is a randomized open label study which will compare the efficacy of the treatment strategy combining Lamivudine and therapeutic vaccine (12 intra-muscular injections of Engerix B over a 6-month period) to a treatment with Lamivudine alone on the control of viral replication in patients with a replicative HBV infection and an increase in transaminases.

Eligible patients have to be HIV, HDV and HCV negative and will have to i) give their written informed consent; ii) have a B hepatitis grade over or equal to F2 with the Metavir score, DNA HBV greater than 105 copies/mL (or 104 copies/mL if Ag Hbe -) , ALAT greater than 1.3 times the upper limit of the normal; iii) accept to have a liver biopsy and to be followed for this protocol at the DHP. After a 3-month treatment with Lamivudine, patients whose viral load is negative or at least decreased by 4 Log will be randomized to the same treatment for a further 9-month period or to the same treatment combined with 12 injections of vaccine over 6 months. The main endpoints are undetectability of HBV DNA blood level 12 months after treatment initiation and 6 months after the end of the treatment. Secondary endpoints will be HBV DNA blood levels at 3, 6, 9 and 12 months after the end of the treatment, transaminases blood level, Lamivudine treatment compliance, the feasibility of the vaccine injections schedule, safety, AgHBe seroconversion (in positive patients) and negativation of AgHBs. Two hundred ten patients have to be included (70 in the Lamivudine group, and 140 in the Lamivudine + vaccine group) in order to show a difference of at least 20% in the percentage of patients with an undetectable viral load at 12 months (70% expected under Lamivudine monotherapy), with a power of 90%, an alpha risk equal to 5% and a bilateral test. Patients with a virological failure will be maintained or retreated with Lamivudine. For the patients with an YMDD mutation, a treatment with Adefovir Dipivoxil will be possible. Patients' inclusion is planned to start in January 2005 and end after 12 or 18 months. Patients will be treated during one year and followed one year without treatment in the study protocol, and then will be managed if necessary

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Liver biopsy acceptation
  • B hepatitis grade over or equal to F2 Metavir score
  • DNA HBV greater than 100000 copies/mL (or 10000 copies/mL if Ag Hbe negative)
  • ALAT greater than 1.3 times the upper normal limit

Exclusion Criteria:

  • HCV, HDV and HIV positive
  • Pregnancy
  • Decompensated liver cirrhosis
  • Pretreated patient
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00120796

Locations
Senegal
Hopital Principal
Dakar, Senegal
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
GlaxoSmithKline
Investigators
Principal Investigator: Papa Saliou Mbaye Hopital Principal de Dakar Senegal
Study Chair: Muriel Vray Institut Pasteur Paris France
  More Information

No publications provided

Responsible Party: Director, ANRS
ClinicalTrials.gov Identifier: NCT00120796     History of Changes
Other Study ID Numbers: ANRS 12100 HEPADAK-2
Study First Received: July 12, 2005
Last Updated: March 28, 2008
Health Authority: Senegal: Ministere de la sante

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:
Hepatitis B
Hepatitis B Vaccines
Lamivudine

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Lamivudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014