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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Alisporivir; Drug: Peginterferon alfa-2a; Drug: Ribavirin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 459
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
      • Novartis Investigative Site
    • Kogarah, New South Wales, Australia, 2217
      • Novartis Investigative Site
    • Westmead, New South Wales, Australia, 2145
      • Novartis Investigative Site
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Novartis Investigative Site
    • Fitzroy, Victoria, Australia, 3065
      • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1070
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• France
  • Nice Cedex 3, France, 06202
    • Novartis Investigative Site
  • Paris, France, 75006
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10969
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Hamburg, Germany, 20099
    • Novartis Investigative Site
  • Köln, Germany, 50937
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
• Hungary
  • Bekescsaba, Hungary, H-5600
    • Novartis Investigative Site
  • Budapest, Hungary, 1083
    • Novartis Investigative Site
  • Budapest, Hungary, 1126
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Kaposvár, Hungary, 7400
    • Novartis Investigative Site
  • Szekesfehervar, Hungary, 8000
    • Novartis Investigative Site
• Italy
  • Bologna, Italy, 40138
    • Novartis Investigative Site
  • FI
    • Antella - Bagno a Ripoli, FI, Italy, 50012
      • Novartis Investigative Site
  • PA
    • Palermo, PA, Italy, 90127
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35128
      • Novartis Investigative Site
  • PR
    • Parma, PR, Italy, 43100
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00161
      • Novartis Investigative Site
• Poland
  • Bialystok, Poland, 15-540
    • Novartis Investigative Site
  • Lódz, Poland, 91-347
    • Novartis Investigative Site
  • Warszawa, Poland, 01-201
    • Novartis Investigative Site
• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Novartis Investigative Site
• Romania
  • Bucharest, Romania, 021105
    • Novartis Investigative Site
  • Bucharest, Romania, 020125
    • Novartis Investigative Site
  • Iasi, Romania, 700506
    • Novartis Investigative Site
  • District 1
    • Bucharest, District 1, Romania, 050526
      • Novartis Investigative Site
  • District 3
    • Bucharest, District 3, Romania, 030317
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28029
    • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41014
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Novartis Investigative Site
  • Keelung City, Taiwan, 20401
    • Novartis Investigative Site
  • Lin-Ko, Taiwan, 33305
    • Novartis Investigative Site
  • Niaosong Township, Taiwan, 83301
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Yun-Lin, Taiwan, 640
    • Novartis Investigative Site
  • Taiwan, ROC
    • Taipei, Taiwan, ROC, Taiwan, 112
      • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Ankara, Turkey, 06800
    • Novartis Investigative Site
  • Fatih / Istanbul, Turkey, 34098
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, W2 1NY
    • Novartis Investigative Site
  • London, United Kingdom, NW3 2PR
    • Novartis Investigative Site
  • London, United Kingdom, E1 1BB
    • Novartis Investigative Site
  • Nottingham, United Kingdom, NG7 2UH
    • Novartis Investigative Site
• United States
  • California
    • San Diego, California, United States, 92101
      • Novartis Investigative Site
    • San Diego, California, United States, 92115
      • Novartis Investigative Site
    • Ventura, California, United States, 93003
      • Novartis Investigative Site
  • Florida
    • Bradenton, Florida, United States, 34209
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32804
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33607
      • Novartis Investigative Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Novartis Investigative Site
    • Honolulu, Hawaii, United States, 96814
      • Novartis Investigative Site
  • Illinois
    • Springfield, Illinois, United States, 62703
      • Novartis Investigative Site
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Novartis Investigative Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Novartis Investigative Site
  • New Jersey
    • Egg Harbor Twp, New Jersey, United States, 08234
      • Novartis Investigative Site
  • New York
    • Brooklyn, New York, United States, 11230
      • Novartis Investigative Site
    • New York, New York, United States, 10021
      • Novartis Investigative Site
  • Texas
    • Arlington, Texas, United States, 76012
      • Novartis Investigative Site
    • Dallas, Texas, United States, 75246-2096
      • Novartis Investigative Site
    • Houston, Texas, United States, 77030
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78215
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A: ALV 600 mg QD; Alisporivir (ALV) 600 mg once daily (QD) with Peginterferon alfa-2a (PEG) and Ribavirin (RBV) for up to 48 weeks	Drug: Alisporivir; ALV 200 mg soft gel capsules administered orally; Other Names: DEB025; ALV; Drug: Peginterferon alfa-2a; PEG 180 μg administered via subcutaneous (s.c.) injection once weekly; Other Names: Pegasys®; PEG; Drug: Ribavirin; RBV 200 mg tablets (weight-based dose: < 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose; Other Names: Copegus®; RBV
Experimental: Treatment B: ALV 800 mg QD; Alisporivir (ALV) 800 mg QD with PEG and RBV for up to 48 weeks	Drug: Alisporivir; ALV 200 mg soft gel capsules administered orally; Other Names: DEB025; ALV; Drug: Peginterferon alfa-2a; PEG 180 μg administered via subcutaneous (s.c.) injection once weekly; Other Names: Pegasys®; PEG; Drug: Ribavirin; RBV 200 mg tablets (weight-based dose: < 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose; Other Names: Copegus®; RBV
Experimental: Treatment C1: ALV Placebo - 600 mg QD; 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; ALV 200 mg soft gel capsules administered orally; Other Names: DEB025; ALV; Drug: Peginterferon alfa-2a; PEG 180 μg administered via subcutaneous (s.c.) injection once weekly; Other Names: Pegasys®; PEG; Drug: Ribavirin; RBV 200 mg tablets (weight-based dose: < 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose; Other Names: Copegus®; RBV; Drug: Placebo; ALV placebo soft gel capsules administered orally; Other Names: ALV Placebo
Experimental: Treatment C2: ALV Placebo - 400 mg BID; 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; ALV 200 mg soft gel capsules administered orally; Other Names: DEB025; ALV; Drug: Peginterferon alfa-2a; PEG 180 μg administered via subcutaneous (s.c.) injection once weekly; Other Names: Pegasys®; PEG; Drug: Ribavirin; RBV 200 mg tablets (weight-based dose: < 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose; Other Names: Copegus®; RBV; Drug: Placebo; ALV placebo soft gel capsules administered orally; Other Names: ALV Placebo
Experimental: Treatment D: ALV 400 mg BID; Alisporivir (ALV) 400 mg twice daily BID with PEG and RBV for up to 48 weeks	Drug: Alisporivir; ALV 200 mg soft gel capsules administered orally; Other Names: DEB025; ALV; Drug: Peginterferon alfa-2a; PEG 180 μg administered via subcutaneous (s.c.) injection once weekly; Other Names: Pegasys®; PEG; Drug: Ribavirin; RBV 200 mg tablets (weight-based dose: < 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose; Other Names: Copegus®; RBV

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Debiopharm International SA

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: August 16, 2010
• First Submitted That Met QC Criteria: August 16, 2010
• First Posted (Estimate): August 17, 2010

Study Record Updates

• Last Update Posted (Estimate): August 25, 2016
• Last Update Submitted That Met QC Criteria: July 14, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Chronic hepatitis C; Cyclophilin inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Peginterferon alfa-2a
• Other Study ID Numbers: CDEB025A2210; 2010-020033-14 (EudraCT Number)