Immunotherapy With TG4040 in Treatment-naïve Patients Chronically Infected With Hepatitis C Virus

• Informed consent obtained and signed;
• Male or female patients;
• With chronic hepatitis C (genotype 1) evidenced by HCV positive serology detectable for more than 6 months;
• Patients with fibrosis status graded F0 or F1 according to the METAVIR grading system; patients with a F2 fibrosis stage could be enrolled on a case-by-case basis after being sure that they have a contraindication to be treated with an IFN-based standard HCV treatment; patients with F3 or F4 fibrosis stage will not be enrolled; this will be assessed either on the liver biopsy performed less than 18 months prior to baseline or on a FibroTest® and a FibroScan® performed within 2 months prior to first TG4040 injection; in case of discordant results, a liver biopsy will be performed prior to TG4040 treatment;;
• Treatment-naïve patients: patients who have never received IFN-based treatment;

• Patients must have compensated liver disease, with:

  • No history of ascites, hepatic encephalopathy or bleeding from esophageal varices;

  • Laboratory tests values:

    • Serum alanine aminotransferase (ALT)less then 2 folds the Upper Limit of Normal (ULN);
    • Serum bilirubin and international normalized ratio (INR) values within normal range (except in patients with Gilbert syndrome where serum bilirubin may be as high as 3.0 mg/dL); and
    • Other laboratory parameters of grade 0 or 1 (CTC criteria);
• For women of child-bearing potential, i.e. with no history of hysterectomy or tubal ligation, a negative pregnancy test at study entry and adequate protection against pregnancy during the conduct of the study and until 3 months after last TG4040 injection.

Additionnal cohorts:

• Patients with high ALT level (2 folds ULN\<ALT\<5 folds ULN in the 2 months before inclusion) and fibrosis not higher than F2.

Exclusion Criteria:

Patients will be excluded from the study for any of the following reasons:

• Co-infection with HBV (indicated by the presence of Hepatitis B Surface Antigen (HBsAg) in serum; patients with anti-hepatitis B core antibody response (anti-HBc) will not be excluded) or HIV (anti-HIV antibodies in serum); patients with HIV positive sexual partner (by history) will not be included;
• Current HCV therapies;
• Active IV drug or alcohol abuse;

• Serious, concomitant disorder, including:

  • primary biliary cirrhosis or sclerosing cholangitis;
  • auto-immune disease such as symptomatic cryoglobulinemia, polyarthritis, multiple sclerosis; a broad auto-immune testing will be performed at baseline;
  • proven or suspected immunosuppressive disorder;
  • active systemic infection; if the patient has acute febrile illness ( > 38°C) on the day of vaccination, it will be delayed by at least one week after complete recovery;
• Malignancy within the last 5 years; patients with history of squamous cell skin cancer or basal cell skin cancer will be enrolled, unless the history of skin cancer is at the vaccination site;
• Systemic corticosteroid therapy or other immunosuppressive/immunomodulating drugs (e.g. Cyclosporine) within 2 months prior to first study drug injection; corticosteroid nasal sprays, inhaled steroids for asthma and/or topical steroids are permissible;
• Participation in another experimental protocol during the study period (last intake of investigational drug within 6 months prior to baseline);
• Breast-feeding women;
• Receipt of any inactivated vaccine 14 days prior to vaccination or for the duration of the study; receipt of any live attenuated vaccine within 30 days prior to vaccination or for the duration of the study;
• Allergy to eggs;
• Patient unable to comply with the protocol requirements;
• Any condition that, in the opinion of the investigator, might interfere with study objectives.