A Study of Debio 025 in Combination With PegIFN Alpha-2a and Ribavirin in Chronic HCV Patients Non-responders to Standard Treatment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Debiopharm International SA
ClinicalTrials.gov Identifier:
NCT00537407
First received: September 28, 2007
Last updated: May 1, 2015
Last verified: May 2015
  Purpose

Debio 025 (alisporivir) is an oral cyclophilin inhibitor with a new mechanism of action demonstrating potent anti-hepatitis C virus (HCV) activity in pre-clinical models and patients.

The current standard of care (SOC) in HCV patients consists of a combination of peg-IFN alpha and ribavirin. Treatment duration and ribavirin dose depend on the genotype treated. Only 40-50% of patients with genotype 1 achieve a sustained viral response (SVR). This study assesses whether Debio 025 administered in combination with peg-IFN alpha 2a and ribavirin can improve the outcome of treatment in this group of patients.


Condition Intervention Phase
Chronic Hepatitis C
Drug: Debio 025
Drug: Peg-IFNα2a
Drug: Ribavirin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Randomized, 5-arm, Parallel-group Study of the Effects on Viral Kinetics, Safety and Pharmacokinetics of Different Dosing Regimens of Debio 025 in Combination With Peginterferon Alpha-2a and Ribavirin in Chronic HCV Genotype 1 Patients Who Are Non Responders to Standard Peginterferon Alpha and Ribavirin Treatment

Resource links provided by NLM:


Further study details as provided by Debiopharm International SA:

Primary Outcome Measures:
  • Change From Baseline in log10 Hepatitis C Virus RNA at Day 29 in the Debio 025 Triple Therapy Treatment Arms (A, D, and E) [ Time Frame: Baseline to Day 29 ] [ Designated as safety issue: No ]
    Hepatitis C virus RNA was quantified in plasma samples using real time polymerase chain reaction.


Secondary Outcome Measures:
  • Change From Baseline in log10 Hepatitis C Virus RNA at Day 29 in the Debio 025 Monotherapy and Dual Therapy Treatment Arms (B and C) [ Time Frame: Baseline to Day 29 ] [ Designated as safety issue: No ]
    Hepatitis C virus RNA was quantified in plasma samples using real time polymerase chain reaction.

  • log10 Hepatitis C Virus RNA at Day 29 [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
    Hepatitis C virus RNA was quantified in plasma samples using real time polymerase chain reaction.

  • Percentage of Participants With a Rapid Viral Response at Day 29 [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
    A participant had a rapid viral response if their viral RNA was undetectable (< 10 IU/mL).

  • Percentage of Participants With an Early Viral Response at Week 12 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    A participant had an early viral response if their viral RNA had decreased ≥ 2 log10 at Week 12 compared to Baseline.

  • Percentage of Participants With an End-of-treatment Response at the End of Treatment (Week 48 or 72) [ Time Frame: End of treatment (Week 48 or 72) ] [ Designated as safety issue: No ]
    A participant had an end-of-treatment response if their viral RNA was undetectable (< 10 IU/mL).

  • Percentage of Participants With a Sustained Viral Response 24 Weeks After the End of Treatment (Week 72 or 96) [ Time Frame: 24 weeks after the end of treatment (Week 72 or 96) ] [ Designated as safety issue: No ]
    A participant had a sustained viral response if their viral RNA was undetectable (< 10 IU/mL).


Enrollment: 50
Study Start Date: September 2007
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm A
Debio 025 (alisporivir) 400 mg orally once daily + peg-IFNα2a 180 μg subcutaneously (sc) once weekly + ribavirin 1000 or 1200 mg/day orally for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response
Drug: Debio 025
Debio 025 supplied as a 100 mg/mL oral solution
Other Name: Alisporivir
Drug: Peg-IFNα2a
Peg-IFNa2a supplied in 180 μg/0.5 mL prefilled syringes
Other Name: PEGASYS
Drug: Ribavirin
Ribavirin supplied as 200 mg tablets
Other Name: Copegus
Experimental: Treatment Arm B
Debio 025 (alisporivir) 400 mg orally once daily for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response
Drug: Debio 025
Debio 025 supplied as a 100 mg/mL oral solution
Other Name: Alisporivir
Drug: Peg-IFNα2a
Peg-IFNa2a supplied in 180 μg/0.5 mL prefilled syringes
Other Name: PEGASYS
Drug: Ribavirin
Ribavirin supplied as 200 mg tablets
Other Name: Copegus
Experimental: Treatment Arm C
Debio 025 (alisporivir) 400 mg orally once daily + peg-IFNα2a 180 μg sc once weekly for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response
Drug: Debio 025
Debio 025 supplied as a 100 mg/mL oral solution
Other Name: Alisporivir
Drug: Peg-IFNα2a
Peg-IFNa2a supplied in 180 μg/0.5 mL prefilled syringes
Other Name: PEGASYS
Drug: Ribavirin
Ribavirin supplied as 200 mg tablets
Other Name: Copegus
Experimental: Treatment Arm D
Debio 025 (alisporivir) 800 mg orally once daily + peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response
Drug: Debio 025
Debio 025 supplied as a 100 mg/mL oral solution
Other Name: Alisporivir
Drug: Peg-IFNα2a
Peg-IFNa2a supplied in 180 μg/0.5 mL prefilled syringes
Other Name: PEGASYS
Drug: Ribavirin
Ribavirin supplied as 200 mg tablets
Other Name: Copegus
Experimental: Treatment Arm E
Debio 025 (alisporivir) orally at a loading dose of 400 mg twice daily for 7 days followed by 400 mg/day for 22 days + peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally for 29 days followed by peg-IFNα2a 180 μg sc once weekly + ribavirin 1000 or 1200 mg/day orally administered for 44 or 68 weeks depending upon response
Drug: Debio 025
Debio 025 supplied as a 100 mg/mL oral solution
Other Name: Alisporivir
Drug: Peg-IFNα2a
Peg-IFNa2a supplied in 180 μg/0.5 mL prefilled syringes
Other Name: PEGASYS
Drug: Ribavirin
Ribavirin supplied as 200 mg tablets
Other Name: Copegus

Detailed Description:

This is a multicentre, open-label, randomized, 5 arm parallel-group, multiple dose study in 50 chronic hepatitis C virus (HCV) genotype 1 non-responders to standard treatment with peg-IFN alpha (2a or 2b) and ribavirin. The entire study lasts a maximum of 96 weeks and consists of a 48- or 72-week treatment period (according to response). A follow-up visit to assess the sustained viral response (SVR) takes place 24 weeks after treatment cessation, i.e., at study Week 72 or 96, or earlier for discontinued study participants.

There were 2 parts in the treatment period. Part 1 lasted from Day 1 to Day 29 (Weeks 1 to 4); Part 2 lasted from Week 5 to Week 48 or 72.

During Part 1 of treatment (Weeks 1 to 4), participants are randomized to 1 of 5 treatment arms and receive 4 weeks of Debio 025 (alisporivir) monotherapy, Debio 025 combined with standard dose peg-IFNα2a, or 1 of 3 triple therapies combining different doses of Debio 025 with peg-IFNα2a and ribavirin at standard doses.

During Part 2 of treatment (Weeks 5 to 48 or 72), participants receive standard doses of peg-IFNα2a/ribavirin dual therapy for 44 or 68 weeks, depending on their response to treatment. At Week 12, participants who do not achieve ≥ 2 log10 decrease in HCV RNA are withdrawn and considered treatment failures. Participants who have undetectable HCV RNA levels and/or ≥ 2 log10 decrease in HCV RNA continue treatment until Week 24. At Week 24, participants who still have detectable HCV RNA levels are withdrawn and considered treatment failures. Participants with undetectable HCV RNA levels at Weeks 12 and 24 continue treatment until Week 48. At Week 24, "slow responders" (defined as participants with a detectable, but > 2 log10 decrease in HCV RNA levels at Week 12 and undetectable levels at Week 24) are eligible to continue treatment until Week 72.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients between 18 and 60 years of age.
  • Hepatitis B negative and human immunodeficiency virus (HIV) negative.
  • Diagnosed with hepatitis C genotype I and not responsive to treatments such as peginterferon alpha-2a or 2b and ribavirin for at least 12 weeks.
  • Adequate liver function (Child-Pugh-Turcotte score A) and other laboratory parameters within acceptable range.
  • Females may participate only if they cannot become pregnant, i.e., are surgically sterile, post-menopausal, or using 2 reliable contraceptive methods.
  • Male patients must be surgically sterile or utilizing a barrier contraceptive method.
  • For female patients of child bearing potential, negative pregnancy test within 1 week of first investigational product administration.

Exclusion Criteria:

  • Treatment with any investigational drug within 6 months prior to the start of the study.
  • Ongoing or recent use of antiviral medication within 1 month before the start of the study.
  • A known bad reaction or intolerance to Debio 025, peginterferon alpha-2a, and/or ribavirin.
  • Presence or history of any severe related disease.
  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: NCT00537407

Locations
United States, California
Scripps Clinic Liver Disease Research Center
la Jolla, California, United States, 92037
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
University of Miami Center for Liver Diseases
Miami, Florida, United States, 33136
United States, Maryland
The Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21205
United States, Texas
Methodist Transplant Physicians
Dallas, Texas, United States, 75203
United States, Virginia
Metropolitan Research
Fairfax, Virginia, United States, 22031
United States, Washington
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Sponsors and Collaborators
Debiopharm International SA
Investigators
Study Director: Raf Crabbé, MD Debiopharm International S.A.
  More Information

Additional Information:
No publications provided

Responsible Party: Debiopharm International SA
ClinicalTrials.gov Identifier: NCT00537407     History of Changes
Other Study ID Numbers: Debio 025-HCV-207
Study First Received: September 28, 2007
Results First Received: April 1, 2015
Last Updated: May 1, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Debiopharm International SA:
Hepatitis
Hepatitis C

Additional relevant MeSH terms:
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Flaviviridae Infections
Hepatitis
Hepatitis, Viral, Human
Liver Diseases
RNA Virus Infections
Virus Diseases
Peginterferon alfa-2a
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015