Alisporivir con pegIFN / RBV in pazienti con epatite C cronica con precedente fallimento terapeutico all'inibitore della proteasi

• Conditions: Chronic hepatitis C genotype 1 protease inhibitor (PI) treatment failure; MedDRA version: 14.1Level: LLTClassification code 10008912Term: Chronic hepatitis CSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2011-004653-31-IT
• Lead Sponsor: OVARTIS FARMA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-29
• Last Update Posted: 10 February 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 173

Inclusion Criteria

1. Written informed consent must be obtained before any study-related assessment is performed; 2. HCV GT1 patients with previous PI treatment failure. PI treatment failure is defined as: •Patients who previously received therapy with ANY HCV protease inhibitor for at least 4 weeks and meets at least one of the following four criteria: -Failed treatment as per approved label stopping rules at time of treatment -Had viral breakthrough on treatment, or relapse after treatment -received at least 4 weeks of any Protease Inhibitor in a clinical trial and did not achieve SVR for any reason. -Discontinued treatment due to an adverse event, provided at least one PI associated mutation is detectable by population sequencing during screening. -The patient has a minimum HCV RNA of 1000 IU/mL at the time of the current study screening 3. Timing of the PI treatment. The therapy with HCV PI was: •The last anti-HCV treatment the patient received prior to the screening of this study. •The minimum time from the last dose of previous PI treatment to the first dose of study medication (DEB025/pegIFN/RBV) is three months. •There is no maximum time limit between the last HCV treatment failure to the first dose of study medication (DEB025/pegIFN/RBV). 4. Males or females aged =18 and = 70 years; 5. Body Mass Index = 18 and = 36 kg/m2; 6. Chronic hepatitis C virus infection diagnosed: a. Positive for anti-HCV antibody, or HCV RNA or an HCV genotype test at least 6 months before screening, with positive HCV RNA tested at the time of screening OR b. Positive for anti-HCV antibody and positive HCV RNA at the time of screening with a liver biopsy within 3 years before the study entry, consistent with chronicity of HCV infection (presence of fibrosis); 7. Serum HCV RNA = 1000 IU/ml (3 log10), assessed by qPCR (quantitative polymerase chain reaction) or equivalent at screening visit, no upper limit; 8. Infection with HCV genotype 1; NOTE: mixed infections with other genotypes will not be eligible; 9. One of the following liver evaluations: •A liver biopsy within 3 years prior to baseline. If cirrhosis has been previously diagnosed with a biopsy there is no need to repeat the biopsy. •Transient Elastography (FibroScan) within 6 months prior to baseline (in countries where Fibroscan is approved). 10. Patients with compensated cirrhosis, defined as Child-Pugh score <6, are eligible unless they meet any of the exclusion criteria.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 73

Exclusion Criteria

1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives of that medication before enrollment, whichever is longer; Current or planned participation to another clinical trial during this study. Participation in observational or registry studies not involving drug therapy is allowed 2 Patients who discontinued treatment during the qualifying course of PI therapy due to a Serious Adverse Event (SAE)that directly lead to treatment discontinuation, or due to a pegIFN or RBV signature” serious adverse event (e.g. neutropenia, anemia, thrombocytopenia, severe depression/psychiatric illness) that directly lead to treatment discontinuation. 3. History of hypersensitivity to any pegIFN or RBV. 4. Any null non-responders to prior pegIFN/RBV treatment, defined as patients who received the pegIFN/RBV treatment prior to the PI therapy, who had = 2 log10 reduction of HCV RNA from the baseline during the first 12 weeks of the previous pegIFN/RBV treatment. 5. Any medical condition associated with high medical risk or contraindicated to use of peg-IFNa and/or RBV treatment as indicated in current product package insert, including known hypersensitivity reactions, such as urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis to interferon alpha or any other product component, erythema multiforme to ribavirin or any other product component, autoimmune disorders, hemoglobinopathies (thalassaemia major, sickle cell anemia or drepanocytosis), creatinine clearance < 50 ml/min, coadministration with didanosine, Hepatic decompensation (Child-Pugh score >6) in cirrhotic CHC patients before or during treatment, history of ischemic and hemorrhagic cerebrovascular disorders, uncontrolled diabetes mellitus (defined by fasting glucose > 7.77 mmol/L (140 mg/dL) and HBA1c > 7.5%) or retinopathy. 6. Active or suspected cancer, or a history of malignancy where the risk of recurrence is = 20% within 2 years 7. HBsAg positive 8. HIV positive 9. Elevated (>ULN) total bilirubin level documented on more than one (>1) occasion during the past 6 months; 10. Presence or history of hepatic decompensation, 11. Hepatocellular carcinoma (HCC) 12. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test either at screening or baseline. 13. Men whose female partners are pregnant or intend to become pregnant while the male patient is receiving study treatment or within 7 months of the last DEB025 or RBV dose. 14. Men UNLESS they are using a condom with spermicide during intercourse while on treatment and for 7 months after the last DEB025 or RBV dose. Male patients should not father a child in this period. 15. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are using highly effective methods of contraception during dosing and for 7 months after the last DEB025 or RBV dose. 16. Use of any other medication (including over the counter medication and herbal products) within 5 drug half-lives of that medication or within 14 days before baseline if half-life is unknown (whichever is longer) that are known inhibitors/inducers of cytochrome 450 3A, substrates of cytochrome 450 3A, substrates of P-gp, or substrates/inhibitors of OATPs, MRP2 or BSEP, and / or are mentioned in the list of prohib

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified