Efficacy and Safety of Alisporivir Triple Therapy in Chronic Hepatitis C Genotype 1 Treatment-naïve Participants

Study Overview
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Brief Summary
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This study will assess the safety and efficacy of alisporivir (ALV; DEB025) triple therapy [i.e., when added to peginterferon alfa-2a (PEG) and ribavirin (RBV)] to optimize treatment in treatment-naïve participants with hepatitis C virus (HCV) genotype 1 (GT1)

Official Title
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A Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of DEB025/Alisporivir in Combination With Peg-IFNα2a and Ribavirin in Hepatitis C Genotype 1 Treatment-naïve Patients

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Alisporivir
* Drug: Peginterferon alfa-2a
* Drug: Ribavirin
* Drug: ALV Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Chronic HCV infection HCV genotype 1 No previous treatment for hepatitis C infection Serum HCV RNA level ≥ 1000 IU/ml assessed by quantitative polymerase chain reaction or equivalent at screening, no upper limit Liver evaluation prior to baseline: liver biopsy within 3 years or Fibroscan within 6 months Exclusion criteria: HCV genotype different from genotype 1 or co-infection with other HCV genotype Co-infection with Hepatitis B or HIV Any other cause of relevant liver disease other than HCV Presence or history of hepatic decompensation Alanine aminotransferase (ALT) ≥ 10 times upper limit of normal (ULN), more than 1 episode of elevated bilirubin (> ULN) in past 6 months Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm A<br>Alisporivir (ALV) 600 mg twice daily (BID) with Peginterferon alfa-2a (PEG) and ribavirin (RBV) for 1 week, followed by an additional 23 or 47 weeks according to response-guided treatment duration (RGT): Participants with a viral load below the level of detection (< LOD) at Week 4 stop study treatment after 24 weeks Participants with a viral load ≥ LOD at Week 4 complete 48 weeks of study treatment | Drug: Alisporivir<br>* ALV 200 mg soft gel capsules administered orally<br>* Other names: ALV;Drug: Peginterferon alfa-2a<br>* PEG 180 μg administered via subcutaneous (s.c.) injection once weekly<br>* Other names: PEG;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: RBV;|
| Experimental: Treatment Arm B<br>Alisporivir (ALV) 400 mg twice daily (BID) with PEG and RBV for 24 or 48 weeks according to response-guided treatment duration (RGT) | Drug: Alisporivir<br>* ALV 200 mg soft gel capsules administered orally<br>* Other names: ALV;Drug: Peginterferon alfa-2a<br>* PEG 180 μg administered via subcutaneous (s.c.) injection once weekly<br>* Other names: PEG;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: RBV;|
| Experimental: Treatment Arm C<br>Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg once daily (QD) for 47 weeks | Drug: Alisporivir<br>* ALV 200 mg soft gel capsules administered orally<br>* Other names: ALV;Drug: Peginterferon alfa-2a<br>* PEG 180 μg administered via subcutaneous (s.c.) injection once weekly<br>* Other names: PEG;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: RBV;|
| Active Comparator: Treatment Arm D<br>ALV Placebo with PEG and RBV for 48 weeks | Drug: Peginterferon alfa-2a<br>* PEG 180 μg administered via subcutaneous (s.c.) injection once weekly<br>* Other names: PEG;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: RBV;Drug: ALV Placebo<br>* ALV placebo soft gel capsules administered orally<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Sustained Virologic Response (SVR) 12 Weeks After the End of Treatment (SVR12) | SVR12 was defined as hepatitis C virus (HCV) RNA laboratory value below the level of quantification (< LOQ; i.e., 25 IU/ml) 12 weeks after the end of treatment. | 12 weeks after the end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved SVR 24 Weeks After the End of Treatment (SVR24) | SVR24 was defined as HCV RNA laboratory value < LOQ 24 weeks after the end of treatment. | 24 weeks after the end of treatment | 
| Percentage of Participants With Rapid Virologic Response (RVR) After 4 Weeks of Treatment (RVR4) | RVR4 was defined as serum HCV RNA < LOQ after 4 weeks of treatment. | after 4 weeks of treatment | 
| Percentage of Participants With Early Virologic Response (EVR) After 12 Weeks of Treatment | EVR was defined as a ≥ 2 log10 decrease in HCV RNA or HCV RNA < LOQ after 12 weeks of treatment. | after 12 weeks of treatment | 
| Percentage of Participants With Partial Early Virologic Response (pEVR) After 12 Weeks of Treatment | pEVR was defined as a ≥ 2 log10 decrease in HCV RNA and still detectable (≥ LOQ) after 12 weeks of treatment. | after 12 weeks of treatment | 
| Percentage of Participants With Complete Early Virologic Response (cEVR) After 12 Weeks of Treatment | cEVR was defined as serum HCV RNA < LOQ after 12 weeks of treatment. | after 12 weeks of treatment | 
| Percentage of Participants With Extended Rapid Virologic Response (eRVR) From 4 to 12 Weeks of Treatment | eRVR was defined as achieving RVR4 and maintaining HCV RNA < LOQ until Week 12. | from 4 to 12 weeks of treatment | 
| Percentage of Participants With End of Treatment Response (ETR) at Treatment End Within 48 Weeks | ETR was defined as serum HCV RNA < LOQ at treatment end (completed or prematurely discontinued). | at treatment end within 48 weeks | 
| Percentage of Participants With Alanine Aminotransferase (ALT) Abnormalities Within 48 Weeks | ALT abnormalities were summarized as participants who had either: ALT > 2 x upper limit of normal (ULN) during the study and > 2 x ULN at baseline ALT > 3 x ULN during the study and > 2 x ULN at baseline | within 48 weeks | 
| Percentage of Participants With Grade 3 or 4 Anemia During Treatment Within 48 Weeks | Grading was according to the Modified Division of Microbiology & Infectious Diseases (DMID) Toxicity Tables (version 2.0). Participants with multiple abnormalities were counted only once in the worst category. | within 48 weeks | 
| Percentage of Participants With Grade 3 or 4 Neutropenia During Treatment Within 48 Weeks | Grading was according to the DMID Toxicity Tables (version 2.0). Participants with multiple abnormalities were counted only once in the worst category. | within 48 weeks | 
| Percentage of Participants With Grade 3 or 4 Thrombocytopenia During Treatment Within 48 Weeks | Grading was according to the DMID Toxicity Tables (version 2.0). Participants with multiple abnormalities were counted only once in the worst category. | within 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic hepatitis C, Cyclophilin inhibitor