Efficacy and Safety of Alisporivir Alone or Combined With RBV or PEG in Chronic Hepatitis C Genotype 2 and 3 Treatment-naïve Participants

A Multicenter, Randomized, Open Label, Parallel-group Phase IIB Study on the Efficacy and Safety of Oral Regimens of DEB025 Alone or in Combination With Ribavirin Versus Standard of Care (Peg-IFNα2a Plus Ribavirin) in Treatment-naïve Hepatitis C Genotype 2 and 3 Patients

The study is to investigate whether alisporivir (ALV; DEB025) alone or in combination with either ribavirin (RBV) or peginterferon alfa-2a (PEG) is more efficient compared to standard of care (PEG+RBV) in treatment-naïve participants with hepatitis C virus (HCV) genotype 2 and 3. In addition, triple therapy with DEB025 plus standard of care will be applied to participants not achieving rapid viral response (RVR) in the different arms.

Study Overview

• Status: Completed
• Conditions: Chronic Pain; Hepatitis C
• Intervention / Treatment: Drug: Alisporivir; Drug: Peginterferon alfa-2a; Drug: Ribavirin

• Study Type: Interventional
• Enrollment (Actual): 340
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
      • Novartis Investigative Site
    • Kogarah, New South Wales, Australia, 2217
      • Novartis Investigative Site
    • Westmead, New South Wales, Australia, 2145
      • Novartis Investigative Site
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
      • Novartis Investigative Center
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Novartis Investigative Site
    • Fitzroy, Victoria, Australia, 3065
      • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1070
    • Novartis Investigative Site
  • Gent, Belgium, 9000
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1H2
      • Novartis Investigative Site
  • Ontario
    • Toronto, Ontario, Canada, M4V 1P7
      • Novartis Investigative Site
• France
  • Clichy Cedex, France, 92118
    • Novartis Investigative Site
  • Creteil, France, 94000
    • Novartis Investigative Site
  • Marseille, France, 13008
    • Novartis Investigative Site
  • Paris, France, 75006
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10969
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Freiburg, Germany, 79095
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
• India
  • Guwahati, India, 781006
    • Novartis Investigative Site
  • Haryana, India, 122001
    • Novartis Investigative Site
  • Hyderabad - Andhra Pradesh, India, 500012
    • Novartis Investigative Site
  • Mumbai, India, 400020
    • Novartis Investigative Site
  • New Delhi, India, 110070
    • Novartis Investigative Site
  • Kerala
    • Trivandrum, Kerala, India, 695607
      • Novartis Investigative Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400036
      • Novartis Investigative Site
  • Punjab
    • Ludhiana, Punjab, India, 141001
      • Novartis Investigative Site
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226014
      • Novartis Investigative Site
• Italy
  • Bologna, Italy, 40138
    • Novartis Investigative Site
  • Brescia, Italy, 25123
    • Novartis Investigative Site
  • Pavia, Italy, 27100
    • Novartis Investigative Site
  • Roma, Italy, 00133
    • Novartis Inestigative Site
  • Torino, Italy, 10126
    • Novartis Investigative Site
• Korea, Republic of
  • Pusan, Korea, Republic of, 614-735
    • Novartis Investigative Site
  • Pusan, Korea, Republic of, 602-739
    • Novartis Inestigative Center
  • Seoul, Korea, Republic of, 738-736
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 120-752
    • Novartis Korea Ltd.
• Poland
  • Bialystok, Poland, 15-540
    • Novartis Investigative Site
  • Lódz, Poland, 91-347
    • Novartis Investigative Site
  • Warsaw, Poland, 01 - 201
    • Novartis Investigative Site
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Fundacion De Investigacion de Diego
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Novartis Investigative Site
  • Niaosong Township, Taiwan, 83301
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, ROC112
    • Novartis Investigative Site
  • Yun-Lin, Taiwan
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
  • Chiang Mai, Thailand, 50200
    • Novartis Investigative Site
  • Songkla, Thailand, 90110
    • Novartis Investigative Site
• United Kingdom
  • Glasgow - Scotland, United Kingdom, G12 OYN
    • Novartis Investigative Site
  • London, United Kingdom, SW17 0QT
    • Novartis Investigative Site
  • London, United Kingdom, W2 1NY
    • Novartis Investigative Site
  • London, United Kingdom, SE5 9RS
    • Novartis Investigative Site
  • London, United Kingdom, E1 1BB
    • Novartis Investigative Site
  • Plymouth, United Kingdom, PL6 8DH
    • Novartis Investigative Site
• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • San Diego, California, United States, 92101
      • Sharp Rees-Stealy Medical Group, Inc.
    • San Diego, California, United States, 92105
      • Research and Education Inc.
    • Ventura, California, United States, 93003
      • Island View Gastroenterology Associates
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawai Medical Center East LLC
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinical Research
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • The Office of Dr. Claudia Martorell
  • Missouri
    • St. Louis, Missouri, United States, 63104
      • Saint Louis University
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0001
      • Dartmouth-Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • New York, New York, United States, 10021
      • Weill Cornell Medical Center
  • Texas
    • Arlington, Texas, United States, 76012
      • The North Texas Research Institute
    • Houston, Texas, United States, 77030
      • Liver Associates of Texas
    • Houston, Texas, United States, 77030
      • Liver Specialist of Texas
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Chronic hepatitis C viral infection
• Plasma HCV RNA level lower limit ≥ 10,000 IU/ml assessed by quantitative polymerase chain reaction (qPCR) or equivalent at screening (no upper limit)
• HCV genotype 2 or 3
• No previous treatment for hepatitis C infection

Exclusion criteria:

• Evidence of cirrhosis at the time of screening
• Evidence of hepatocellular carcinoma at the time of screening
• Any other cause of relevant liver disease other than HCV
• Alanine aminotransferase (ALT) ≥ 10 times upper limit of normal (ULN)
• Other protocol-defined inclusion/exclusion criteria may 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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALV 1000 mg; Alisporivir (ALV) 600 mg twice daily (BID) for 1 week, followed by ALV 1000 mg once daily (QD) during Weeks 2 to 24.	Drug: Alisporivir; ALV 200 mg soft gel capsules administered orally; Other Names: DEB025; ALV
Experimental: ALV 600 mg+RBV; Alisporivir (ALV) 600 mg BID with RBV for 1 week, followed by ALV 600 mg QD with ribavirin (RBV) during Weeks 2 to 24.	Drug: Alisporivir; ALV 200 mg soft gel capsules administered orally; Other Names: DEB025; ALV; Drug: Ribavirin; RBV 400 mg (2 x 200 mg tablets) administered orally twice daily (BID); Other Names: Copegus®; RBV
Experimental: ALV 800 mg+RBV; Alisporivir (ALV) 600 mg BID with RBV for 1 week, followed by ALV 800 mg QD with RBV during Weeks 2 to 24.	Drug: Alisporivir; ALV 200 mg soft gel capsules administered orally; Other Names: DEB025; ALV; Drug: Ribavirin; RBV 400 mg (2 x 200 mg tablets) administered orally twice daily (BID); Other Names: Copegus®; RBV
Experimental: ALV 600 mg+PEG; Alisporivir (ALV) 600 mg BID with Peginterferon alfa-2a (PEG) for 1 week, followed by ALV 600 mg QD with PEG once weekly during Weeks 2 to 24.	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
Active Comparator: PEG+RBV; Peginterferon alfa-2a (PEG) and RBV during Weeks 1 to 24.	Drug: Peginterferon alfa-2a; PEG 180 μg administered via subcutaneous (s.c.) injection once weekly; Other Names: Pegasys®; PEG; Drug: Ribavirin; RBV 400 mg (2 x 200 mg tablets) administered orally twice daily (BID); Other Names: Copegus®; RBV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Rapid Viral Response (RVR) After 4 Weeks of Treatment < the Limit of Quantification (RVR4LOQ)	RVR4LOQ was defined as RVR [serum hepatitis C virus (HCV) ribonucleic acid (RNA) < the limit of quantification (LOQ), i.e., < 25 IU/mL], after 4 weeks of treatment.	after 4 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With RVR After 4 Weeks of Treatment < the Limit of Detection (RVR4LOD)	RVR4LOD was defined as Rapid Viral Response (RVR) [serum HCV RNA < the limit of detection (LOD), i.e., < 10 IU/mL], after 4 weeks of treatment.	after 4 weeks of treatment
Percentage of Participants With RVR4LOQ and RVR4LOD (Genotype 2)		after 4 weeks of treatment
Percentage of Participants With RVR4LOQ and RVR4LOD (Genotype 3)		after 4 weeks of treatment
Percentage of Participants With Complete Early Viral Response (cEVR) After 12 Weeks of Treatment (cEVR12LOQ and cEVR12LOD)	cEVR12LOQ and cEVR12LOD were defined as cEVR [serum HCV RNA < LOQ and < LOD] after 12 weeks of treatment, respectively.	after 12 weeks of treatment
Percentage of Participants With cEVR12LOQ and cEVR12LOD (Genotype 2)		after 12 weeks of treatment
Percentage of Participants With cEVR12LOQ and cEVR12LOD (Genotype 3)		after 12 weeks of treatment
Percentage of Participants With End of Treatment Response (ETR) Within 24 Weeks (ETR24LOQ and ETR24LOD)	ETR24LOQ and ETR24LOD were defined as ETR [serum HCV RNA < LOQ and < LOD] after 24 weeks of treatment or when prematurely discontinued.	at end of treatment, within 24 weeks
Percentage of Participants With ETR24LOQ and ETR24LOD (Genotype 2)		at end of treatment, within 24 weeks
Percentage of Participants With ETR24LOQ and ETR24LOD (Genotype 3)		at end of treatment, within 24 weeks
Percentage of Participants With RVR Who Achieved Sustained Viral Response (SVR) 12 Weeks After the End of Treatment (SVR12LOQ and SVR12LOD)	SVR12LOQ and SVR12LOD were defined as Sustained Viral Response (SVR) [serum HCV RNA < LOQ and < LOD] 12 weeks after treatment, respectively.	12 weeks after the end of treatment
Percentage of Participants With RVR Who Achieved SVR12LOQ and SVR12LOD (Genotype 2)		12 weeks after the end of treatment
Percentage of Participants With RVR Who Achieved SVR12LOQ and SVR12LOD (Genotype 3)		12 weeks after the end of treatment
Percentage of Participants With RVR Who Achieved SVR at 24 Weeks After the End of Treatment (SVR24LOQ and SVR24LOD)		24 weeks after the end of treatment
Percentage of Participants With RVR Who Achieved SVR24LOQ and SVR24LOD (Genotype 2)		24 weeks after the end of treatment
Percentage of Participants With RVR Who Achieved SVR24LOQ and SVR24LOD (Genotype 3)		24 weeks after the end of treatment
Percentage of Participants With On-treatment Viral Breakthrough	Viral breakthrough was defined as either: Confirmed increase of HCV RNA ≥1 log10 above nadir (nadir = lowest HCV RNA value during treatment), or; HCV RNA becoming ≥ 100 IU/mL after previously being undetectable (< LOD) during treatment	within 24 weeks of treatment
Percentage of Participants With Viral Relapse	Viral relapse was defined as having reappearance of detectable HCV RNA after previously being undetectable (< LOD) during treatment.	within 24 weeks after the end of treatment

Collaborators and Investigators

• Sponsor: Debiopharm International SA

Publications and helpful links

General Publications

• Pawlotsky JM, Flisiak R, Sarin SK, Rasenack J, Piratvisuth T, Chuang WL, Peng CY, Foster GR, Shah S, Wedemeyer H, Hezode C, Zhang W, Wong KA, Li B, Avila C, Naoumov NV; VITAL-1 study team. Alisporivir plus ribavirin, interferon free or in combination with pegylated interferon, for hepatitis C virus genotype 2 or 3 infection. Hepatology. 2015 Oct;62(4):1013-23. doi: 10.1002/hep.27960. Epub 2015 Aug 10.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: October 5, 2010
• First Submitted That Met QC Criteria: October 5, 2010
• First Posted (Estimate): October 6, 2010

Study Record Updates

• Last Update Posted (Estimate): August 30, 2016
• Last Update Submitted That Met QC Criteria: July 20, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: 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; Pain; Neurologic Manifestations; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Chronic Pain; Hepatitis A; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Peginterferon alfa-2a
• Other Study ID Numbers: CDEB025A2211; 2010-020034-26 (EudraCT Number)