chronic HCV infection MedDRA version: 9.1 Level: LLT Classification code 10019183 Term: HCV
Conditions
Interventions
Trade Name: Vesanoid
Product Name: Tretinoin
Product Code: Ro 01-5488
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Tretinoin
Concentration unit: mg milligram(s)
Concentration type: equal
Co
Sponsors
Universitätsmedizin der Johannes-Gutenberg Universität Mainz
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Serological evidence of chronic Hepatitis-C infection by positive anti-HCV testing and detectable HCV-RNA in serum (>100 IE/ml) Non-responder to the previous anti-HCV combination therapy with pegylated Interferon and Ribavirin. Non-response is defined as a lack of at least a > 2 log drop in HCV-RNA at any time point during the previous therapy of at least 12 weeks, or a > 2 log drop at week 12, but HCV-RNA still detectable at week 24. During the previous course Peginterferon and Ribavirin had to be administered in standard dose, that is e.g. at least 1.0 µg/kg/body weight/week Peginterferon alfa-2b and 800 mg/d Ribavirin at the beginning or at least 135 µg/week Peginterferon alfa-2a and 800 mg/d Ribavirin at the beginning. Evidence of HCV Genotype 1 by means of reverse hybridisation assay Inno LiPA from Bayer Versant (Innogenetics) within 24 months before randomisation Histological evidence of inflammation and fibrosis (> F1) in the liver with or without evidence of compensated cirrhosis within 24 months before randomisation (Child-Pugh grade A) The previous anti-HCV therapy course had to be finished at least 6 months before randomisation into this study Men and women aged 18 to 65 years Negative urine- or serum-pregnancy test for women with childbearing potential within 24 hours before administration of the first dose of medication (also for fertile female partners of male patients) For female patients: During administration of the study medication and during 6 months of treatment free follow-up two highly effective methods of contraception have to be used, one of them with a barrier function, that is condom; (Note for guidance on non-clinical safety studies for the conduct of human clinical trials for pharmaceuticals, CPMP/ICH/286/95 mod); micro-dosed gestagenes („Minipille“) and oral contraceptives with a content of =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Known hypersensitivity to the active substance of Peginterferon alfa-2a, to alfa-interferons or Ribavirin or one of the other ingredients Known allergy to a substance of the class of retinoids or one of the other ingredients (e.g. allergy to soy beans or peanuts) Persons under age or persons of age, that are not able to realize nature, meaning and significance of the clinical study and to adjust their will in that sense (according to § 40 Abs. 4 and § 41 Abs. 2 and Abs. 3 AMG) Pregnancy or breastfeeding Fertile women, not using highly effective methods of contraception Male partners of pregnant women Participation in another clinical study at the same time or within the last three months Patients already included once into this study Persons, that are eventually in dependence on the sponsor or investigator Infection with HCV-Genotypes-2, -3, -4, -5 or -6 Evidence of HBsAg, HIV-antibodies during screening Patients under immunosuppression Treatment with systemic anti-neoplastic or immune modulatory medication (including supraphysiological oses of steroids or radiation) within the last 6 months before randomisation and throughout the whole study duration Chronic hepatitis unrelated to Hepatitis-C-virus (e.g. Hemochromatosis, Autoimmunehepatitis, metabolic- or alcohol-related liver disease) Decompensated cirrhosis or liver disease graded Child-Pugh grade B or C Signs of a hepatocellular carcinoma before randomisation in case of a state of cirrhosis or transition to cirrhosis (_-Fetoprotein values > 100 ng/ml lead to exclusion of the patient from the study, with values of -Fetoproteins of > 50 ng/ml and 1,5 mg/dl during screening Acute or known psychic illnesses or disturbances that negatively influence the ability of the patient to understand the requirements of this study Severe depression in the medical history, defined as any sign on suicidal tendencies, or hospitalisation because of depression, or any exclusively antidepressive therapy of at least 3 months duration (an accompanying antidepressive treatment in the setting of a previous anti-HCV therapy with Interferons is allowed) Severe psychotic or any other severe psychiatric disease in the medical history, defined as any antipsychotic or otherwise psychiatric treatment of at least 3 months duration in the medical history or any sign on suicidal tendencies or hospitalisation because of these illnesses Patients with the state of excitation or irritation Patients with delirant syndromes as well as exogenious psychosis in their medical history Epilepsia Autoimmune diseases (e.g. chronic inflammatory bowel disease, idiopathic thrombocytopenic Purpura, Lupus erythematodes, Sklerodermia, severe Psoriasis, rheumatoid Arthritis) Disturbances in thyroid function, impossible to adjust euthyreod by medication Insufficiently adjusted Diabetes mellitus (HbA1c > 7%) or insufficiently adjusted hypertriglyceridemia (> 350 mg/dl) Clinically manifest gout Chronic pulmonary disease with functional restriction Severe cardiac disease (e.g. cardiac insufficiency NYHA
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the parameter of HCV viral kinetics under therapy with the combination of Peginterferon alfa-2a, Ribavirin and All-trans Retinoic acid vs. the combination of Peginterferon alfa-2a and Ribavirin. ;Secondary Objective: Comparison of the virological response rates and the immunological responses between treatment groups Evaluation of safety and tolerability of combination therapy with Peginterferon alfa-2a, Ribavirin and All-trans Retinoic acid;Primary end point(s): To compare the parameter M delta (corresponding to an increase in the elimination rate of infected hepatocytes during treatment) of HCV viral kinetics for therapy with the combination of Peginterferon alfa-2a, Ribavirin and All-trans Retinoic acid vs. the combination of Peginterferon alfa-2a and Ribavirin. Based on viral load measurements at BL, days 1, 2, 3, weeks 1, 2, 3, 4, 6, 8 and 12 (treatment groups A and B) by means of the Roche COBAS Ampliprep /COBAS TaqMan Test (lower limit of detection <12 IU/ ml) M delta will be determined for each individual patient. | — |
Countries
Germany
Outcome results
None listed