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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Debiopharm International SA
ClinicalTrials.gov Identifier:
NCT01183169
First received: August 16, 2010
Last updated: July 14, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Hepatitis C
Drug: Alisporivir
Drug: Peginterferon alfa-2a
Drug: Ribavirin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Debiopharm International SA:

Primary Outcome Measures:
  • Percentage of Participants With Complete Early Viral Response Below the Limit of Quantification (cEVR-LOQ) [ Time Frame: after 12 weeks of treatment ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With Complete Early Viral Response Below the Limit of Detection (cEVR-LOD) [ Time Frame: after 12 weeks of treatment ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Achieved Sustained Viral Response 12 Weeks After Treatment (SVR12)-LOQ and SVR12-LOD [ Time Frame: 12 weeks after treatment ] [ Designated as safety issue: No ]
    SVR12-LOQ and SVR12-LOD were defined as serum HCV RNA < LOQ and serum HCV RNA < LOD 12 weeks after treatment, respectively.

  • Percentage of Participants Who Achieved Sustained Viral Response 24 Weeks After Treatment (SVR24)-LOQ and SVR24-LOD [ Time Frame: 24 weeks after treatment ] [ Designated as safety issue: No ]
    SVR24-LOQ and SVR24-LOD were defined as serum HCV RNA < LOQ and serum HCV RNA < LOD 24 weeks after treatment, respectively.

  • Percentage of Participants With Rapid Viral Response (RVR)-LOQ and RVR-LOD [ Time Frame: after 4 weeks of treatment ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Partial Early Virologic Response After 12 Weeks of Treatment (pEVR)-LOQ and pEVR-LOD [ Time Frame: after 12 weeks of treatment ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With End of Treatment Response (ETR)-LOQ and ETR-LOD [ Time Frame: within 48 weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Had Normalized ALT at Treatment End and Study End [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With On-treatment Viral Breakthrough [ Time Frame: within 48 weeks ] [ Designated as safety issue: No ]

    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

  • Percentage of Participants With Viral Relapse [ Time Frame: within 24 weeks after treatment ] [ Designated as safety issue: No ]
    Viral relapse was defined as reappearance of detectable HCV RNA after previously being undetectable (< LOQ) during treatment.


Enrollment: 459
Study Start Date: August 2010
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01183169

  Show 75 Study Locations
Sponsors and Collaborators
Debiopharm International SA
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Debiopharm International SA
ClinicalTrials.gov Identifier: NCT01183169     History of Changes
Other Study ID Numbers: CDEB025A2210  2010-020033-14 
Study First Received: August 16, 2010
Results First Received: July 14, 2016
Last Updated: July 14, 2016
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Spain: Spanish Agency of Medicines
Taiwan: Department of Health
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Debiopharm International SA:
Chronic hepatitis C
Cyclophilin inhibitor

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Peginterferon alfa-2a
Interferon-alpha
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016