Alisporivir With RBV in Chronic Hepatitis C Genotype 2 and 3 Participants for Whom Interferon is Not an Option

A Multicenter, Open-label, Randomized, 2-arm, Phase II Trial of Pharmacodynamics, Pharmacokinetics and Safety of Two Dose Regimens of DEB025/Alisporivir in Combination With Ribavirin Therapy in Chronic Hepatitis C Genotype 2 and 3 Patients Who Have Previously Failed Interferon Therapy or Are Intolerant or Unable to Take Interferon.

The primary purpose of this study is to evaluate the pharmacodynamic (i.e. hepatitis C virus (HCV) viral load), pharmacokinetic and safety profiles between two treatment groups receiving different doses of DEB025 in combination with ribavirin (RBV) during the first 12 weeks treatment in chronic hepatitis C genotype (GT)-2 and GT-3 patients who had previously failed interferon therapy or were intolerant or unable to take interferon.

Study Overview

• Status: Completed
• Conditions: Hepatitis C; Liver Disease
• Intervention / Treatment: Drug: Ribavirin; Drug: Alisporivir

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Clichy, France, 92110
    • Novartis Investigative Site
  • Creteil, France, 94010
    • Novartis Investigative Site
  • Lyon Cedex 04, France, 69317
    • Novartis Investigative Site
  • Nice Cedex 3, France, 06202
    • Novartis Investigative Site
  • Paris, France, 75014
    • Novartis Investigative Site
• United States
  • California
    • Bakersfield, California, United States, 93301
      • Novartis Investigative Site
    • Lancaster, California, United States, 93534
      • Novartis Investigative Site
    • San Diego, California, United States, 92114
      • Novartis Investigative Site
    • San Diego, California, United States, 92128
      • Novartis Investigative Site
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Novartis Investigative Site
  • Texas
    • Arlington, Texas, United States, 76012
      • Novartis Investigative Site
    • Houston, Texas, United States, 77030
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78215
      • Novartis Investigative Site
  • Virginia
    • Newport News, Virginia, United States, 23602
      • Novartis Investigative Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Novartis Investigative Site
    • Seattle, Washington, United States, 98101
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed
2. Participants with HCV genotype 2 or 3 infection who have previously failed interferon therapy or are intolerant or unable to take interferon
3. Males or females aged ≥18 years
4. Diagnosed Chronic hepatitis C virus infection

Exclusion criteria:

1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of that medication before enrollment
2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
3. Hepatitis B surface antigen (HBsAg) positive
4. Human immunodeficiency virus (HIV) positive

Other protocol-defined inclusion/exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alisporivir 300 mg BID; Alisporivir (ALV) 300 mg twice daily (BID) with ribavirin for 12 or 24 weeks based on Week 2 response, with a safety follow-up of at least 4 weeks, during which patients did not receive any study medication	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®; Drug: Alisporivir; ALV 100 and 200 mg soft gel capsules administered orally; Other Names: DEB025
Experimental: Alisporivir 400 mg BID; ALV 400 mg twice daily (BID) with ribavirin for 12 or 24 weeks based on Week 2 response, with a safety follow-up of at least 4 weeks, during which patients did not receive any study medication	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®; Drug: Alisporivir; ALV 100 and 200 mg soft gel capsules administered orally; Other Names: DEB025

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hepatitis C Virus Ribonucleic Acid Viral Load at Week 12	The change in log transformed Hepatitis-C Virus (HCV) Ribonucleic acid (RNA) from baseline to Week 12.	Baseline, Week 12
Change From Baseline in Alanine Aminotransferase (ALT) at Week 12	ALT levels were assessed as part of clinical chemistry assessments throughout the study as a measure of biochemical liver recovery. A negative change from baseline indicates less liver damage.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Sustained Virologic Response (SVR) 4, 12, and 24 Weeks After Treatment	SVR is defined as HCV RNA less than the lower limit of quantification (LLOQ), i.e., <15 IU/mL, at 4 weeks (SVR4), 12 weeks (SVR12), and 24 weeks (SVR24) after treatment, respectively.	Up to 24 weeks posttreatment
Percentage of Participants With Extended Rapid Virologic Response	Extended rapid virologic response (eRVR) was defined as serum HCV RNA < LLOQ after 2 weeks of treatment	2 weeks
Percentage of Participants With Rapid Virologic Response (RVR)	eRVR was defined as serum HCV RNA < LLOQ after 4 weeks of treatment	4 weeks
Percentage of Participants With End of Treatment Response (ETR)	ETR was defined as serum HCV RNA < LLOQ at treatment end (completed or prematurely discontinued).	Up to 24 weeks
Percentage of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Had Normalized ALT at Treatment End and Study End	ALT is an enzyme found mostly in the cells of the liver and kidney. When the liver is damaged, ALT is released into the blood. This makes ALT a common test for liver damage, because higher ALT levels may indicate more liver damage. ALT upper limit of normal is commonly considered to be 40 international units per liter (IU/L), so abnormal ALT is above 40 IU/L.	Up to 24 weeks

Collaborators and Investigators

• Sponsor: Debiopharm International SA

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: March 18, 2014
• First Submitted That Met QC Criteria: March 20, 2014
• First Posted (Estimate): March 21, 2014

Study Record Updates

• Last Update Posted (Estimate): October 13, 2016
• Last Update Submitted That Met QC Criteria: August 19, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Interferon intolerant; Cyclophilin inhibitor; Chronic hepatitis C genotype 2; Chronic hepatitis C genotype 3
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Liver Diseases; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin
• Other Study ID Numbers: CDEB025A2233; 2013-003751-38 (EudraCT Number)