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

Phase 2

Completed

• Conditions: Chronic Hepatitis C
• Interventions: Drug: Debio 025; Drug: Peg-IFNα2a; Drug: Ribavirin

• Registration Number: NCT00537407
• Lead Sponsor: Debiopharm International SA

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 At Week 12, participants who do not achieve ≥ 2 log10 decrease in HCV RNA are withdrawn and considered treatment failures.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 At Week 24, participants who still have detectable HCV RNA levels are withdrawn and considered treatment failures.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 Timeline

• Study Start: 2007-09
• Study First Submitted: 2007-09-28
• Study First Submitted QC: 2007-09-28
• Study First Posted: 2007-10-01
• Primary Completion: 2010-04
• Study Completion: 2010-04
• Disposition First Submitted: 2014-08-04
• Disposition First Submitted QC: 2014-08-04
• Disposition First Posted: 2014-08-05
• Results First Submitted: 2015-04-01
• Results First Submitted QC: 2015-05-01
• Results First Posted: 2015-05-07
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-12
• Last Update Posted: 2016-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm B	Peg-IFNα2a	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
Treatment Arm A	Debio 025	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
Treatment Arm C	Peg-IFNα2a	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
Treatment Arm E	Peg-IFNα2a	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
Treatment Arm A	Peg-IFNα2a	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
Treatment Arm B	Debio 025	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
Treatment Arm D	Debio 025	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
Treatment Arm E	Debio 025	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
Treatment Arm C	Debio 025	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
Treatment Arm D	Peg-IFNα2a	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
Treatment Arm A	Ribavirin	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
Treatment Arm B	Ribavirin	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
Treatment Arm C	Ribavirin	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
Treatment Arm D	Ribavirin	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
Treatment Arm E	Ribavirin	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

Primary Outcome Measures

Name	Time	Method
Change From Baseline in log10 Hepatitis C Virus RNA at Day 29 in the Debio 025 Triple Therapy Treatment Arms (A, D, and E)	Baseline to Day 29	Hepatitis C virus RNA was quantified in plasma samples using real time polymerase chain reaction.

Secondary Outcome Measures

Name	Time	Method
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)	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	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	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	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)	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)	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).

Trial Locations

Locations (7)

Scripps Clinic Liver Disease Research Center; 🇺🇸 la Jolla, California, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

University of Miami Center for Liver Diseases; 🇺🇸 Miami, Florida, United States

Methodist Transplant Physicians; 🇺🇸 Dallas, Texas, United States

Metropolitan Research; 🇺🇸 Fairfax, Virginia, United States

Virginia Mason Medical Center; 🇺🇸 Seattle, Washington, United States

The Johns Hopkins University School of Medicine; 🇺🇸 Baltimore, Maryland, United States