Alisporivir With RBV in Chronic Hepatitis C Genotype 2 and 3 Participants for Whom Interferon is Not an Option

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the pharmacodynamic (i.e. hepatitis C virus (HCV) viral load), pharmacokinetic and safety profiles between two treatment groups receiving different doses of DEB025 in combination with ribavirin (RBV) during the first 12 weeks treatment in chronic hepatitis C genotype (GT)-2 and GT-3 patients who had previously failed interferon therapy or were intolerant or unable to take interferon.

Official Title
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A Multicenter, Open-label, Randomized, 2-arm, Phase II Trial of Pharmacodynamics, Pharmacokinetics and Safety of Two Dose Regimens of DEB025/Alisporivir in Combination With Ribavirin Therapy in Chronic Hepatitis C Genotype 2 and 3 Patients Who Have Previously Failed Interferon Therapy or Are Intolerant or Unable to Take Interferon.

Conditions
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Hepatitis C, Liver Disease

Intervention / Treatment
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* Drug: Alisporivir
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed Participants with HCV genotype 2 or 3 infection who have previously failed interferon therapy or are intolerant or unable to take interferon Males or females aged ≥18 years Diagnosed Chronic hepatitis C virus infection Exclusion criteria: Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of that medication before enrollment History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes Hepatitis B surface antigen (HBsAg) positive Human immunodeficiency virus (HIV) positive Other protocol-defined inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alisporivir 300 mg BID<br>Alisporivir (ALV) 300 mg twice daily (BID) with ribavirin for 12 or 24 weeks based on Week 2 response, with a safety follow-up of at least 4 weeks, during which patients did not receive any study medication | Drug: Alisporivir<br>* ALV 100 and 200 mg soft gel capsules administered orally<br>* Other names: DEB025;Drug: Ribavirin<br>* RBV 200 mg tablets (weight-based dose: < 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose<br>* Other names: Copegus®;|
| Experimental: Alisporivir 400 mg BID<br>ALV 400 mg twice daily (BID) with ribavirin for 12 or 24 weeks based on Week 2 response, with a safety follow-up of at least 4 weeks, during which patients did not receive any study medication | Drug: Alisporivir<br>* ALV 100 and 200 mg soft gel capsules administered orally<br>* Other names: DEB025;Drug: Ribavirin<br>* RBV 200 mg tablets (weight-based dose: < 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose<br>* Other names: Copegus®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hepatitis C Virus Ribonucleic Acid Viral Load at Week 12 | The change in log transformed Hepatitis-C Virus (HCV) Ribonucleic acid (RNA) from baseline to Week 12. | Baseline, Week 12 | 
| Change From Baseline in Alanine Aminotransferase (ALT) at Week 12 | ALT levels were assessed as part of clinical chemistry assessments throughout the study as a measure of biochemical liver recovery. A negative change from baseline indicates less liver damage. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Sustained Virologic Response (SVR) 4, 12, and 24 Weeks After Treatment | SVR is defined as HCV RNA less than the lower limit of quantification (LLOQ), i.e., <15 IU/mL, at 4 weeks (SVR4), 12 weeks (SVR12), and 24 weeks (SVR24) after treatment, respectively. | Up to 24 weeks posttreatment | 
| Percentage of Participants With Extended Rapid Virologic Response | Extended rapid virologic response (eRVR) was defined as serum HCV RNA < LLOQ after 2 weeks of treatment | 2 weeks | 
| Percentage of Participants With Rapid Virologic Response (RVR) | eRVR was defined as serum HCV RNA < LLOQ after 4 weeks of treatment | 4 weeks | 
| Percentage of Participants With End of Treatment Response (ETR) | ETR was defined as serum HCV RNA < LLOQ at treatment end (completed or prematurely discontinued). | Up to 24 weeks | 
| Percentage of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Had Normalized ALT at Treatment End and Study End | ALT is an enzyme found mostly in the cells of the liver and kidney. When the liver is damaged, ALT is released into the blood. This makes ALT a common test for liver damage, because higher ALT levels may indicate more liver damage. ALT upper limit of normal is commonly considered to be 40 international units per liter (IU/L), so abnormal ALT is above 40 IU/L. | Up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic hepatitis C genotype 2, Chronic hepatitis C genotype 3, Cyclophilin inhibitor, Interferon intolerant