Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Debiopharm International SA
ClinicalTrials.gov Identifier:
NCT01318694
First received: March 17, 2011
Last updated: August 5, 2016
Last verified: August 2016
  Purpose
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)

Condition Intervention Phase
Hepatitis C
Drug: Alisporivir
Drug: Peginterferon alfa-2a
Drug: Ribavirin
Drug: ALV Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Debiopharm International SA:

Primary Outcome Measures:
  • Percentage of Participants Who Achieved Sustained Virologic Response (SVR) 12 Weeks After the End of Treatment (SVR12) [ Time Frame: 12 weeks after the end of treatment ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants Who Achieved SVR 24 Weeks After the End of Treatment (SVR24) [ Time Frame: 24 weeks after the end of treatment ] [ Designated as safety issue: No ]
    SVR24 was defined as HCV RNA laboratory value < LOQ 24 weeks after the end of treatment.

  • Percentage of Participants With Rapid Virologic Response (RVR) After 4 Weeks of Treatment (RVR4) [ Time Frame: after 4 weeks of treatment ] [ Designated as safety issue: No ]
    RVR4 was defined as serum HCV RNA < LOQ after 4 weeks of treatment.

  • Percentage of Participants With Early Virologic Response (EVR) After 12 Weeks of Treatment [ Time Frame: after 12 weeks of treatment ] [ Designated as safety issue: No ]
    EVR was defined as a ≥ 2 log10 decrease in HCV RNA or HCV RNA < LOQ after 12 weeks of treatment.

  • Percentage of Participants With Partial Early Virologic Response (pEVR) After 12 Weeks of Treatment [ Time Frame: after 12 weeks of treatment ] [ Designated as safety issue: No ]
    pEVR was defined as a ≥ 2 log10 decrease in HCV RNA and still detectable (≥ LOQ) after 12 weeks of treatment.

  • Percentage of Participants With Complete Early Virologic Response (cEVR) After 12 Weeks of Treatment [ Time Frame: after 12 weeks of treatment ] [ Designated as safety issue: No ]
    cEVR was defined as serum HCV RNA < LOQ after 12 weeks of treatment.

  • Percentage of Participants With Extended Rapid Virologic Response (eRVR) From 4 to 12 Weeks of Treatment [ Time Frame: from 4 to 12 weeks of treatment ] [ Designated as safety issue: No ]
    eRVR was defined as achieving RVR4 and maintaining HCV RNA < LOQ until Week 12.

  • Percentage of Participants With End of Treatment Response (ETR) at Treatment End Within 48 Weeks [ Time Frame: at treatment end within 48 weeks ] [ Designated as safety issue: No ]
    ETR was defined as serum HCV RNA < LOQ at treatment end (completed or prematurely discontinued).

  • Percentage of Participants With Alanine Aminotransferase (ALT) Abnormalities Within 48 Weeks [ Time Frame: within 48 weeks ] [ Designated as safety issue: No ]

    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

  • Percentage of Participants With Grade 3 or 4 Anemia During Treatment Within 48 Weeks [ Time Frame: within 48 weeks ] [ Designated as safety issue: No ]

    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.


  • Percentage of Participants With Grade 3 or 4 Neutropenia During Treatment Within 48 Weeks [ Time Frame: within 48 weeks ] [ Designated as safety issue: No ]
    Grading was according to the DMID Toxicity Tables (version 2.0). Participants with multiple abnormalities were counted only once in the worst category.

  • Percentage of Participants With Grade 3 or 4 Thrombocytopenia During Treatment Within 48 Weeks [ Time Frame: within 48 weeks ] [ Designated as safety issue: No ]
    Grading was according to the DMID Toxicity Tables (version 2.0). Participants with multiple abnormalities were counted only once in the worst category.


Enrollment: 1081
Study Start Date: March 2011
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm A

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
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 Arm B
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
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 Arm C
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg once daily (QD) for 47 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
Active Comparator: Treatment Arm D
ALV Placebo with PEG and RBV for 48 weeks
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: ALV Placebo
ALV placebo soft gel capsules administered orally
Other Name: Placebo

  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 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.

  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: NCT01318694

  Show 147 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: NCT01318694     History of Changes
Other Study ID Numbers: CDEB025A2301  2010-022867-37 
Study First Received: March 17, 2011
Results First Received: August 5, 2016
Last Updated: August 5, 2016
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Korea: Food and Drug Administration
Taiwan: Department of Health
Thailand: Food and Drug Administration
Vietnam: Ministry of Health
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Mexico: Federal Commission for Sanitary Risks Protection
Canada: Health Canada
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
Russia: Ministry of Health of the Russian Federation
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Spanish Agency of Medicines
Belgium: Federal Agency for Medicinal Products and Health Products
Hong Kong: Department of Health

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

Additional relevant MeSH terms:
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Hepatitis A
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
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 December 02, 2016