Demonstration of the clinical efficacy and safety of a therapeutic vaccine for the treatment of chronic hepatitis B

Objective

- To demonstrate that therapeutic vaccination can effectively and safely induce a total cure of the disease in patients with chronic hepatitis B.
- To demo ,strate the efficacy of therapeutic hepatitis B vaccination in larger number of patients of chronic hepatitis B patients in different populations
- To demonstrate the feasibility of the concept of therapeutic vaccines for chronic infectious diseases.

Current therapies for chronic hepatitis B (CHB) have limited efficacy with a poor safety profile and comes at a very high cost. CHB is not due a direct cytopathogenic effect of the virus but rather to a chronic and inadequate immune response against the infected hepatocytes together with a state of immune tolerance towards the virus. The role of a therapeutic vaccine is to revert the state cf tolerance and induce a strong and specific immune response against the infected hepatocytes. To achieve this, a vaccine formulation containing 3 recombinant hepatitis B surface antigens (S + preS1 + preS2) together with potent ans specific adjuvants which stimulate mainly the Th1-type cellular immune response and cytotoxic T-cell activity will be used.
Clinical studies to run in parallel in different countries wiil enrol the following adult patient populations: patients with HBeAg positive CHB, patients with HBeAg negative CHB (pre core mutant pattern) and patients with compensa.ed cirrhosis due to hepatitis B infection. After a 3 to 6-month baseline period, the patients will be randomly allocated to receive several doses of either vaccine or placebo. They will followed up to one year after completion of therapy to evaluate the safety and efficacy of the vaccine. Efficacy endpoint wili be assessed on the ability to induce the elimination of serum HBV-DNA and/or the disappearance of HBeAg and the appearance of anti-HBe antibodies. Other secondary endpoint to be evaluated will be the efficacy o, the vaccine to normalise ALT/AST levels in patients and the induction of anti-HBs antibodies. Safety will be assessed by an active monitoring of adverse and serious adverse events, local and general clinical signs and symptoms after vaccination and haematological and hepatic function parameters
The wider use of an effective and a safer therapeutic hepatitis B vaccine wili decrease the risk of cirrhosis and hepatocellular carcinoma in patients. The size of virus reservoir and the incidence of the hepatitis B disease will also be reduced.

Programme(s)

• FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998

Topic(s)

• 8.2 - Demonstration

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Smithkline Beecham Biologicals S.A

Address

89,Rue De L'institut
1330 Rixensart
Belgium

Participants (11)

Academisch Ziekenhuis Utrecht

Netherlands

Address

100,Heidelberglaan 100
3584 CX Utrecht

Azienda Ospedaliera S. Giovanni Battista

Italy

Address

Corso Bramante 88
10126 Torino

HANNOVER MEDICAL SCHOOL

Germany

Address

1,Carl-neuberg-strasse 1
30623 Hannover

HOSPITAL CLINIC BARCELONA

Spain

Address

170,Villaroel 170 Hospital Clinic
08036 Barcelona

Hvidovre University Hospital of København

Denmark

Address

30,Kettegård Alle
2650 Hvidovre

Universitat Autonoma de Barcelona

Spain

Address

Passeig Vall D'hebron 119
08035 Barcelona

Universiteit Gent

Belgium

Address

185,De Pintelaan 185
9000 Gent

University of Athens

Greece

Address

114,Vasilissis Sophias Avenue 114
11527 Athens

University of Göteborg

Sweden

Address

416 85 Göteborg

Université Catholique de Louvain

Belgium

Address

10,Avenue Hippocrate 10
1200 Bruxelles

Université Claude Bernard Lyon 1

France

Address

1,Place De L'hôpital 1
69288 Lyon