Hepatitis C, Chronic
Conditions
Brief summary
The primary objective is to determine the safety of sub-cutaneous (SC) injections of TG4040 in non-cirrhotic, treatment-naïve patients chronically infected with HCV (genotype 1). Patients will be sequentially treated at an escalting dose of TG4040. All patients will be followed up to at least 6 months after his/her first injection. In addition, all patients treated at the highest dose will receive a TG4040 boost injection 6 months after the first injection, and will be followed up during an additional 6-month period.
Detailed description
The first nine patients will be sequentially treated in three cohorts of three patients, i.e. they will receive 3 SC injections of TG4040 on Days 1, 8 and 15, at the dose of 10e6 pfu (first cohort), 10e7 pfu (second cohort), or 10e8 pfu (third cohort). There will be a one-week safety interval between the first injection of the patients of a given cohort, and a two-week safety interval between the last injection of the last patient of a given cohort and the first injection of the first patient of the next one. There will be also a two-week safety observation period after the last injection of the last patient of the third cohort. If the dose of 10e8 pfu does not raise safety problems, then 6 patients will be further enrolled, without safety intervals between patients. They will receive 3 SC injections of TG4040 at the dose of 10e8 pfu, on Days 1, 8 and 15. All patients will be followed up to at least 6 months after his/her first injection. In addition, all patients treated at the dose of 10e8 pfu will receive a TG4040 boost injection 6 months after the first injection, and will be followed up during an additional 6-month period. Three additional cohorts of 9 patients will receive a boost injection either at 2, 4 or 6 months.
Interventions
BIOLOGICALMVA-HCV (Immunotherapy)
MVA-HCV
Sponsors
Transgene
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety (adverse events, vital signs, physical examination, standard laboratory tests) | regularly |
Secondary
| Measure | Time frame |
|---|---|
| Virology (quantification of HCV-RNA), immunology (cellular-mediated and humoral immune responses) | regularly |
Countries
France
Outcome results
None listed