Efficacy and Safety of Adding Alisporivir (DEB025) to Peginterferon (IFN) Alfa-2a (Peg-IFN Alfa-2a) and Ribavirin in Chronic HCV Genotype 1 Patients Who Relapsed or Did Not Respond to Previous Treatment

Study Overview
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Brief Summary
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The study is to investigate whether participants with hepatitis C virus (HCV) genotype 1 who have a history of non-response/relapse to peginterferon alfa-2a (PEG) and ribavirin (RBV) may benefit from treatment with triple therapy alisporivir (ALV; DEB025) with PEG and RBV versus placebo with PEG and RBV.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Phase II Study on Efficacy and Safety of DEB025 Combined With Peg-IFN Alfa-2a and Ribavirin in Chronic Hepatitis C Genotype 1 Relapsers and Non-responders to Previous Peg-IFN Alfa-2 Plus Ribavirin Treatment

Conditions
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Hepatitis C

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


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Chronic HCV genotype 1 viral infection HCV RNA ≥ 1,000 IU/ml assessed by quantitative polymerase chain reaction (qPCR) or equivalent at screening Previous non-responders/relapsers to PEG and RBV after treatment for at least 12 weeks Exclusion criteria: Treatment with any anti-HCV drug (whether approved or investigational) within 3 months prior to screening Women of child-bearing potential unless using highly effective Any other cause of relevant liver disease other than HCV 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 A: ALV 600 mg QD<br>Alisporivir (ALV) 600 mg once daily (QD) with Peginterferon alfa-2a (PEG) and Ribavirin (RBV) for up to 48 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;|
| Experimental: Treatment B: ALV 800 mg QD<br>Alisporivir (ALV) 800 mg QD with PEG and RBV for up to 48 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;|
| Experimental: Treatment C1: ALV Placebo - 600 mg QD<br>ALV Placebo with PEG and RBV for up to 48 weeks; participants not achieving complete early virologic response (cEVR) after 12 weeks of treatment may switch to active ALV 600 mg QD with PEG and RBV. | 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;Drug: Placebo<br>* ALV placebo soft gel capsules administered orally<br>* Other names: ALV Placebo;|
| Experimental: Treatment C2: ALV Placebo - 400 mg BID<br>ALV Placebo with PEG and RBV for up to 48 weeks; participants not achieving cEVR after 12 weeks of treatment may switch to active ALV 400 mg twice daily (BID) with PEG and RBV. | 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;Drug: Placebo<br>* ALV placebo soft gel capsules administered orally<br>* Other names: ALV Placebo;|
| Experimental: Treatment D: ALV 400 mg BID<br>Alisporivir (ALV) 400 mg twice daily BID with PEG and RBV for up to 48 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;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Early Viral Response Below the Limit of Quantification (cEVR-LOQ) | cEVR-LOQ was defined as serum HCV RNA below the limit of quantification (< LOQ; i.e., 25 IU/mL) after 12 weeks of treatment. Post-switch groups were assessed 12 weeks after the switch. | after 12 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Early Viral Response Below the Limit of Detection (cEVR-LOD) | cEVR-LOD was defined as serum HCV RNA below the limit of detection (< LOD; i.e., 10 IU/mL) after 12 weeks of treatment. Post-switch groups were assessed 12 weeks after the switch. | after 12 weeks of treatment | 
| Percentage of Participants Who Achieved Sustained Viral Response 12 Weeks After Treatment (SVR12)-LOQ and SVR12-LOD | SVR12-LOQ and SVR12-LOD were defined as serum HCV RNA < LOQ and serum HCV RNA < LOD 12 weeks after treatment, respectively. | 12 weeks after treatment | 
| Percentage of Participants Who Achieved Sustained Viral Response 24 Weeks After Treatment (SVR24)-LOQ and SVR24-LOD | SVR24-LOQ and SVR24-LOD were defined as serum HCV RNA < LOQ and serum HCV RNA < LOD 24 weeks after treatment, respectively. | 24 weeks after treatment | 
| Percentage of Participants With Rapid Viral Response (RVR)-LOQ and RVR-LOD | RVR-LOQ and RVR-LOD were defined as serum HCV RNA < LOQ and serum HCV RNA < LOD after 4 weeks of treatment, respectively. Post-switch groups were assessed 4 weeks after the switch. | after 4 weeks of treatment | 
| Percentage of Participants With Partial Early Virologic Response After 12 Weeks of Treatment (pEVR)-LOQ and pEVR-LOD | pEVR-LOQ and pEVR-LOD were defined as a ≥ 2 log10 decrease in HCV RNA and still detectable (≥ LOQ and ≥ LOD, respectively) after 12 weeks of treatment. Post-switch groups were assessed 12 weeks after the switch. | after 12 weeks of treatment | 
| Percentage of Participants With End of Treatment Response (ETR)-LOQ and ETR-LOD | ETR-LOQ and ETR-LOD were defined as serum HCV RNA < LOQ and serum HCV RNA < LOD at treatment end (completed or prematurely discontinued), respectively. | within 48 weeks | 
| Percentage of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Had Normalized ALT at Treatment End and Study End |  | Up to 48 weeks | 
| Percentage of Participants With On-treatment Viral Breakthrough | On-treatment viral breakthrough was defined as either: Confirmed increase of HCV RNA ≥1 log10 above nadir (nadir = lowest HCV RNA value during treatment), or HCV RNA becoming ≥ 100 IU/mL after previously being undetectable (< LOQ) during treatment | within 48 weeks | 
| Percentage of Participants With Viral Relapse | Viral relapse was defined as reappearance of detectable HCV RNA after previously being undetectable (< LOQ) during treatment. | within 24 weeks after treatment | 

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