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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00537407
Recruitment Status : Completed
First Posted : October 1, 2007
Results First Posted : May 7, 2015
Last Update Posted : February 17, 2016
Sponsor:
Information provided by (Responsible Party):
Debiopharm International SA

Tracking Information
First Submitted Date  ICMJE September 28, 2007
First Posted Date  ICMJE October 1, 2007
Results First Submitted Date  ICMJE April 1, 2015
Results First Posted Date  ICMJE May 7, 2015
Last Update Posted Date February 17, 2016
Study Start Date  ICMJE September 2007
Actual Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2015)
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 ]
Hepatitis C virus RNA was quantified in plasma samples using real time polymerase chain reaction.
Original Primary Outcome Measures  ICMJE
 (submitted: September 28, 2007)
Log10 HCV RNA change from baseline after 29 days of therapy
Change History Complete list of historical versions of study NCT00537407 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2015)
  • 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 ]
    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 ]
    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 ]
    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 ]
    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) ]
    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) ]
    A participant had a sustained viral response if their viral RNA was undetectable (< 10 IU/mL).
Original Secondary Outcome Measures  ICMJE
 (submitted: September 28, 2007)
Viral response rates(Rapid Viral Resp.[week 4],Early Viral Resp.[week 12],End Treatment Resp.,Sustained Viral Resp.[24 weeks after end treatment],Safety parameters(AEs,safety lab.data,vital signs,ECGs),Drug pharmacokinetics.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Debio 025 in Combination With PegIFN Alpha-2a and Ribavirin in Chronic HCV Patients Non-responders to Standard Treatment
Official Title  ICMJE 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
Brief Summary

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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Hepatitis C
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: Debio 025
    • Drug: Peg-IFNα2a
    • Drug: Ribavirin
  • 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
    Interventions:
    • Drug: Debio 025
    • Drug: Peg-IFNα2a
    • Drug: Ribavirin
  • 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
    Interventions:
    • Drug: Debio 025
    • Drug: Peg-IFNα2a
    • Drug: Ribavirin
  • 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
    Interventions:
    • Drug: Debio 025
    • Drug: Peg-IFNα2a
    • Drug: Ribavirin
  • 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
    Interventions:
    • Drug: Debio 025
    • Drug: Peg-IFNα2a
    • Drug: Ribavirin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 28, 2007)
50
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 2010
Actual Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00537407
Other Study ID Numbers  ICMJE Debio 025-HCV-207
DEB025A2207 ( Other Identifier: Sponsor Code )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Debiopharm International SA
Study Sponsor  ICMJE Debiopharm International SA
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Raf Crabbé, MD Debiopharm International S.A.
PRS Account Debiopharm International SA
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP