HCV infected patients who are incomplete responders to standard pegylated interferon/ribavirin (dual therapy) or pegylated interferon/ribavirin plus a protease inhibitor (triple therapy) MedDRA version: 16.1 Level: LLT Classification code 10066936 Term: HCV viral load System Organ Class: 100000004848
Conditions
Sponsors
Rottapharm S.p.A
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients meeting all the following inclusion criteria will be eligible for enrollment in the study: 1.Signed and dated informed consent obtained before undergoing any trial-specific procedure 2.Male and female patients; age between 18 and 70 years inclusive 3.Chronic hepatitis C infection with genotype confirmed by genotypic testing 4.Meeting a predefined virologic stopping rule to an ongoing standard of care antiviral treatment regimen [containing pegylated interferon-a 2a/b and ribavirin either alone (dual therapy) or in combination with selective HCV protease inhibitors (triple therapy)] 5.detectable HCVRNA levels at the time of screening as follows: - for the Group 1: GT1 patients with HCV-RNA =10.000 IU/mL; - for the Exploratory Group (Group 2): GT1 patients with HCV-RNA >10.000 IU/mL but =30.000 IU/mL and any non-GT1 patient =30.000 IU/mL. 6.Ability to communicate, participate, and comply with the requirements of the entire study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 170 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: Disease related criteria: 1.Co-Infection with HIV and/or HBV 2.Evidence or history in the previous 5 years of deconpensated liver cirrhosis as signs of ascites, esophageal varices or laboratory abnormalities that indicate impaired liver function 3.Evidence of liver disease due to causes other than chronic HCV infection 4.Bilirubin levels > 2.0 mg/dL unless explained by Gilbert’s disease 5.Platelet Count 35 kg/m2 6.Females of childbearing potential: -Pregnancy (i.e. positive pregnancy test at screening) or lactation -Failure to agree to practice adequate contraception methods (e.g. oral contraceptives, intra-uterine device [IUD], transdermal contraceptive patch) 7.Male patients not vasectomized, who do not agree to abstain from intercourse or who do not use a condom 8.Use of concomitant medication that is not allowed and that cannot be discontinued for the entire study period 9.Use of other investigational drugs/treatments, or enrolment in a clinical study within the previous 3 months or 5 half lives (whichever is longer), except for investigational drug/treatments for HCV 10.Known hypersensitivity to any of the test materials or related compounds 11.Use of illicit drugs or significant alcohol abuse within the past 12 months. Use of cannabis is not exclusionary 12.Active autoimmune disease 13.History of moderate, severe or uncontrolled psychiatric disease, especially severe depression and prior suicidal attempt 14.Poor venous access 15.Patients with Creatinin >1,5 ULN 16.Any other condition that, in the opinion of the Investigator, may jeopardize the study conduct according to the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether a short course of Legalon® SIL added to antiviral standard treatment can induce a complete virological response in hepatitis C patients with incomplete response to dual or triple antiviral therapy;Primary end point(s): Study Part I: Complete Virological response at the End-of-treatment (EOT), defined as undetectable HCV-RNA levels at the end of the treatment period. Study Part II: Sustained Virological Response-12 (SVR-12), i.e. undetectable HCV-RNA levels lasting until 12 weeks after the completion of the SOC treatment course.;Timepoint(s) of evaluation of this end point: Study Part I: HCV-RNA levels collected on day 8 and HCV-RNA levels collected after treatment infusion on day 12. Study Part II:HCV-RNA levels collected on week 12 after the end of SOC treatment course.;Secondary Objective: -To determine the optimal dose (20 mg/kg vs. 30 mg/kg) and treatment duration (5 vs. 10 vs. 12 days) of Legalon® SIL for this treatment strategy; -To assess the efficacy of Legalon® SIL in a variety of clinically meaningful virological responses; -To assess the safety and tolerability of Legalon® SIL in the context of chronic hepatitis C and HCV antiviral treatment; -To assess potential resistance mutations selected before, at the end of, and after Legalon® SIL treatment and their influence on virological response. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Study Part I: •Evaluation of the complete virological response (defined as undetectable HCV-RNA levels) according to the different dose regimens; •Evaluation of the complete virological response (defined as undetectable HCV-RNA levels) according to the different treatment durations; •Number of patients with virological breakthrough (during SOC maintenance therapy); •Evaluation of viral kinetics (area under the curve (AUC) and slope of serum HCV-RNA concentration over time); •Normalization of Serum Alanine Aminotransferase (ALT) values at the end of treatment phase; •Improvement of Serum Alanine Aminotransferase (ALT) values at the end of treatment phase; •Viral mutations (primarly in NS4B and/or NS3) associated with resistance to treatment. Study Part II: •Undetectable HCV-RNA levels at the completion of the SOC treatment course; •SVR-24, i.e. undetectable HCV-RNA levels lasting until 24 weeks after completion of the SOC treatment course [SVR-24] (end of follow-up phase); •Number of patients with virological breakthrough and/or relapse during the maintenance treatment follow-up phase; •Viral resistance associated with resistance to treatment; •Normalization of Serum Alanine Aminotransferase (ALT) values 2 weeks after the beginning of the study PART II; •Improvement of Serum Alanine Aminotransferase (ALT) values 2 weeks after the beginning of the study PART II; •Normalization of Serum Alanine Aminotransferase (ALT) values at the completion of the SOC treatment course; •Improvement of Serum Alanine Aminotransferase (ALT) values at the completion of the SOC treatment course; •Normalization of Serum Alanine Aminotransferase (ALT) values at the end of follow-up; •Improvement of Serum Alanine Aminotransferase (ALT) values at the end of follow-up; •Correlation between EOT, SVR and relapse and levels of HCV RNA at baseline of Study PART I and at week 2 of Study PART II; •Fibrosis stage. Safety endpoints: • Adverse Events (A | — |
Countries
Austria, Germany
Contacts
Public ContactClinical Research Department
Rottapharm S.p.A
Outcome results
None listed