Efficacy and Safety of Alisporivir Alone or Combined With RBV or PEG in Chronic Hepatitis C Genotype 2 and 3 Treatment-naïve Participants

Study Overview
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Brief Summary
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The study is to investigate whether alisporivir (ALV; DEB025) alone or in combination with either ribavirin (RBV) or peginterferon alfa-2a (PEG) is more efficient compared to standard of care (PEG+RBV) in treatment-naïve participants with hepatitis C virus (HCV) genotype 2 and 3. In addition, triple therapy with DEB025 plus standard of care will be applied to participants not achieving rapid viral response (RVR) in the different arms.

Official Title
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A Multicenter, Randomized, Open Label, Parallel-group Phase IIB Study on the Efficacy and Safety of Oral Regimens of DEB025 Alone or in Combination With Ribavirin Versus Standard of Care (Peg-IFNα2a Plus Ribavirin) in Treatment-naïve Hepatitis C Genotype 2 and 3 Patients

Conditions
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Hepatitis C, Chronic Pain

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


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Chronic hepatitis C viral infection Plasma HCV RNA level lower limit ≥ 10,000 IU/ml assessed by quantitative polymerase chain reaction (qPCR) or equivalent at screening (no upper limit) HCV genotype 2 or 3 No previous treatment for hepatitis C infection Exclusion criteria: Evidence of cirrhosis at the time of screening Evidence of hepatocellular carcinoma at the time of screening Any other cause of relevant liver disease other than HCV Alanine aminotransferase (ALT) ≥ 10 times upper limit of normal (ULN) 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALV 1000 mg<br>Alisporivir (ALV) 600 mg twice daily (BID) for 1 week, followed by ALV 1000 mg once daily (QD) during Weeks 2 to 24. | Drug: Alisporivir<br>* ALV 200 mg soft gel capsules administered orally<br>* Other names: ALV;|
| Experimental: ALV 600 mg+RBV<br>Alisporivir (ALV) 600 mg BID with RBV for 1 week, followed by ALV 600 mg QD with ribavirin (RBV) during Weeks 2 to 24. | Drug: Alisporivir<br>* ALV 200 mg soft gel capsules administered orally<br>* Other names: ALV;Drug: Ribavirin<br>* RBV 400 mg (2 x 200 mg tablets) administered orally twice daily (BID)<br>* Other names: RBV;|
| Experimental: ALV 800 mg+RBV<br>Alisporivir (ALV) 600 mg BID with RBV for 1 week, followed by ALV 800 mg QD with RBV during Weeks 2 to 24. | Drug: Alisporivir<br>* ALV 200 mg soft gel capsules administered orally<br>* Other names: ALV;Drug: Ribavirin<br>* RBV 400 mg (2 x 200 mg tablets) administered orally twice daily (BID)<br>* Other names: RBV;|
| Experimental: ALV 600 mg+PEG<br>Alisporivir (ALV) 600 mg BID with Peginterferon alfa-2a (PEG) for 1 week, followed by ALV 600 mg QD with PEG once weekly during Weeks 2 to 24. | 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;|
| Active Comparator: PEG+RBV<br>Peginterferon alfa-2a (PEG) and RBV during Weeks 1 to 24. | Drug: Peginterferon alfa-2a<br>* PEG 180 μg administered via subcutaneous (s.c.) injection once weekly<br>* Other names: PEG;Drug: Ribavirin<br>* RBV 400 mg (2 x 200 mg tablets) administered orally twice daily (BID)<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 Rapid Viral Response (RVR) After 4 Weeks of Treatment < the Limit of Quantification (RVR4LOQ) | RVR4LOQ was defined as RVR [serum hepatitis C virus (HCV) ribonucleic acid (RNA) < the limit of quantification (LOQ), i.e., < 25 IU/mL], after 4 weeks of treatment. | after 4 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With RVR After 4 Weeks of Treatment < the Limit of Detection (RVR4LOD) | RVR4LOD was defined as Rapid Viral Response (RVR) [serum HCV RNA < the limit of detection (LOD), i.e., < 10 IU/mL], after 4 weeks of treatment. | after 4 weeks of treatment | 
| Percentage of Participants With RVR4LOQ and RVR4LOD (Genotype 2) |  | after 4 weeks of treatment | 
| Percentage of Participants With RVR4LOQ and RVR4LOD (Genotype 3) |  | after 4 weeks of treatment | 
| Percentage of Participants With Complete Early Viral Response (cEVR) After 12 Weeks of Treatment (cEVR12LOQ and cEVR12LOD) | cEVR12LOQ and cEVR12LOD were defined as cEVR [serum HCV RNA < LOQ and < LOD] after 12 weeks of treatment, respectively. | after 12 weeks of treatment | 
| Percentage of Participants With cEVR12LOQ and cEVR12LOD (Genotype 2) |  | after 12 weeks of treatment | 
| Percentage of Participants With cEVR12LOQ and cEVR12LOD (Genotype 3) |  | after 12 weeks of treatment | 
| Percentage of Participants With End of Treatment Response (ETR) Within 24 Weeks (ETR24LOQ and ETR24LOD) | ETR24LOQ and ETR24LOD were defined as ETR [serum HCV RNA < LOQ and < LOD] after 24 weeks of treatment or when prematurely discontinued. | at end of treatment, within 24 weeks | 
| Percentage of Participants With ETR24LOQ and ETR24LOD (Genotype 2) |  | at end of treatment, within 24 weeks | 
| Percentage of Participants With ETR24LOQ and ETR24LOD (Genotype 3) |  | at end of treatment, within 24 weeks | 
| Percentage of Participants With RVR Who Achieved Sustained Viral Response (SVR) 12 Weeks After the End of Treatment (SVR12LOQ and SVR12LOD) | SVR12LOQ and SVR12LOD were defined as Sustained Viral Response (SVR) [serum HCV RNA < LOQ and < LOD] 12 weeks after treatment, respectively. | 12 weeks after the end of treatment | 
| Percentage of Participants With RVR Who Achieved SVR12LOQ and SVR12LOD (Genotype 2) |  | 12 weeks after the end of treatment | 
| Percentage of Participants With RVR Who Achieved SVR12LOQ and SVR12LOD (Genotype 3) |  | 12 weeks after the end of treatment | 
| Percentage of Participants With RVR Who Achieved SVR at 24 Weeks After the End of Treatment (SVR24LOQ and SVR24LOD) |  | 24 weeks after the end of treatment | 
| Percentage of Participants With RVR Who Achieved SVR24LOQ and SVR24LOD (Genotype 2) |  | 24 weeks after the end of treatment | 
| Percentage of Participants With RVR Who Achieved SVR24LOQ and SVR24LOD (Genotype 3) |  | 24 weeks after the end of treatment | 
| Percentage of Participants With On-treatment Viral Breakthrough | 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 (< LOD) during treatment | within 24 weeks of treatment | 
| Percentage of Participants With Viral Relapse | Viral relapse was defined as having reappearance of detectable HCV RNA after previously being undetectable (< LOD) during treatment. | within 24 weeks after the end of treatment | 

 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