A Study of Hepatitis C Virus (HCV) Polymerase Inhibitor Pro-Drug in Combination With PEGASYS Plus COPEGUS Compared With PEGASYS Plus COPEGUS in Patients With Chronic Hepatitis C Genotype 1 Infection.

A Randomized, Double-blinded Study to Evaluate the Safety and Effect on Sustained Virological Response of HCV Polymerase Inhibitor Pro-drug in Combination With PEGASYS Plus Copegus, Compared With the Currently Approved Combination of PEGASYS Plus Copegus, in Treatment-naïve Patients With Chronic he

This 7 arm study will determine the optimal treatment combination, based on efficacy and safety. Patients with chronic hepatitis C (CHC), genotype 1, will be randomized to one of 7 treatment groups. Groups 1, 2, 4, 5 and 6 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (at doses of 500, 1000 or 1500mg po bid) plus PEGASYS (90 or 180 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd). Group 3 will receive HCV polymerase inhibitor pro-drug 500mg po bid plus PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd for 24 weeks; after 24 weeks, those achieving a rapid virological response (RVR) will stop all medication, and non-RVR patients will remain on triple combination for an additional 24 weeks. Group 7 will receive standard of care (SOC) for 48 weeks. There will be a 24 week period of treatment-free follow-up for all treatment groups. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: Copegus; Drug: Pegasys; Drug: Pegasys; Drug: RO4588161; Drug: RO4588161; Drug: RO4588161

• Study Type: Interventional
• Enrollment (Actual): 516
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
  • Greenslopes, Australia, 4120
  • Melbourne, Australia, 3004
  • Sydney, Australia, 2050
  • Sydney, Australia, 2145
• Austria
  • Wien, Austria, 1090
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
    • Vancouver, British Columbia, Canada, V5Z 1H2
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
    • Toronto, Ontario, Canada, M5G 1L7
• France
  • Clichy, France, 92118
  • Creteil, France, 94010
  • Marseille, France, 13285
  • Paris, France, 75014
  • Paris, France, 75651
  • Pessac, France, 33604
  • Vandoeuvre-les-nancy, France, 54511
• Germany
  • Berlin, Germany, 13353
  • Frankfurt Am Main, Germany, 60590
  • Freiburg, Germany, 79106
  • Hamburg, Germany, 20246
  • Hannover, Germany, 30625
  • Köln, Germany, 50937
• Italy
  • Bologna, Italy, 40138
  • Napoli, Italy, 80131
  • Torino, Italy, 10126
• Puerto Rico
  • Santurce, Puerto Rico, 00909
• Spain
  • Badalona, Spain, 08915
  • Barcelona, Spain, 08003
  • Madrid, Spain, 28222
  • Sevilla, Spain, 41014
  • Valencia, Spain, 46014
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
  • California
    • La Jolla, California, United States, 92037-1030
    • Long Beach, California, United States, 90822
    • Sacramento, California, United States, 95817
    • San Diego, California, United States, 92103-8465
    • San Diego, California, United States, 92154
    • San Francisco, California, United States, 94115
  • Colorado
    • Aurora, Colorado, United States, 80045
    • Englewood, Colorado, United States, 80110
  • Florida
    • Bradenton, Florida, United States, 34209
    • Gainesville, Florida, United States, 32610-0214
    • Miami, Florida, United States, 33136-1051
  • Illinois
    • Chicago, Illinois, United States, 60637
  • Maryland
    • Baltimore, Maryland, United States, 21287
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
  • New York
    • Bronx, New York, United States, 10468
    • Manhasset, New York, United States, 11030
    • New York, New York, United States, 10021
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7584
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0595
  • Oregon
    • Portland, Oregon, United States, 97239
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
  • Tennessee
    • Nashville, Tennessee, United States, 37211
  • Texas
    • Dallas, Texas, United States, 75203
    • Fort Sam Houston, Texas, United States, 78234-3879
    • San Antonio, Texas, United States, 78215
  • Utah
    • Salt Lake City, Utah, United States, 84121
  • Virginia
    • Fairfax, Virginia, United States, 22031
    • Richmond, Virginia, United States, 23249

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients, 18-65 years of age;
• chronic hepatitis C, genotype 1;
• chronic liver disease consistent with CHC;
• compensated liver disease.

Exclusion Criteria:

• infection with any HCV genotype other than genotype 1;
• previous treatment for CHC;
• medical condition associated with chronic liver disease other than CHC;
• HIV, hepatitis A, hepatitis B infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Group 1 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (1000 po bid) plus PEGASYS (180 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd).	Drug: Copegus; 1000/1200mg po daily for 24 weeks; Drug: Pegasys; 180 micrograms sc weekly for 24 weeks; Drug: Pegasys; 90 micrograms sc weekly for 24 weeks; Drug: RO4588161; 1000mg po bid for 24 weeks; Drug: RO4588161; 500mg po bid for 24 weeks; Drug: RO4588161; 1500mg po bid for 24 weeks
Experimental: Group 2; Group 2 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (500 mg po bid) plus PEGASYS (180 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd).	Drug: Copegus; 1000/1200mg po daily for 24 weeks; Drug: Pegasys; 180 micrograms sc weekly for 24 weeks; Drug: Pegasys; 90 micrograms sc weekly for 24 weeks; Drug: RO4588161; 1000mg po bid for 24 weeks; Drug: RO4588161; 500mg po bid for 24 weeks; Drug: RO4588161; 1500mg po bid for 24 weeks
Experimental: Group 3; Group 3 will receive HCV polymerase inhibitor pro-drug 500mg po bid plus PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd for 24 weeks; after 24 weeks, those achieving a rapid virological response (RVR) will stop all medication, and non-RVR patients will remain on triple combination for an additional 24 weeks.	Drug: Copegus; 1000/1200mg po daily for 24 weeks; Drug: Pegasys; 180 micrograms sc weekly for 24 weeks; Drug: Pegasys; 90 micrograms sc weekly for 24 weeks; Drug: RO4588161; 1000mg po bid for 24 weeks; Drug: RO4588161; 500mg po bid for 24 weeks; Drug: RO4588161; 1500mg po bid for 24 weeks
Experimental: Group 4; Group 4 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (1500 mg po bid) plus PEGASYS (90 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd).	Drug: Copegus; 1000/1200mg po daily for 24 weeks; Drug: Pegasys; 180 micrograms sc weekly for 24 weeks; Drug: Pegasys; 90 micrograms sc weekly for 24 weeks; Drug: RO4588161; 1000mg po bid for 24 weeks; Drug: RO4588161; 500mg po bid for 24 weeks; Drug: RO4588161; 1500mg po bid for 24 weeks
Experimental: Group 5; Group 5 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (1000 mg po bid) plus PEGASYS (90 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd).	Drug: Copegus; 1000/1200mg po daily for 24 weeks; Drug: Pegasys; 180 micrograms sc weekly for 24 weeks; Drug: Pegasys; 90 micrograms sc weekly for 24 weeks; Drug: RO4588161; 1000mg po bid for 24 weeks; Drug: RO4588161; 500mg po bid for 24 weeks; Drug: RO4588161; 1500mg po bid for 24 weeks
Experimental: Group 6; Group 6 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (500 mg po bid) plus PEGASYS (90 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd).	Drug: Copegus; 1000/1200mg po daily for 24 weeks; Drug: Pegasys; 180 micrograms sc weekly for 24 weeks; Drug: Pegasys; 90 micrograms sc weekly for 24 weeks; Drug: RO4588161; 1000mg po bid for 24 weeks; Drug: RO4588161; 500mg po bid for 24 weeks; Drug: RO4588161; 1500mg po bid for 24 weeks
Active Comparator: Group 7; Standard of care (SOC)	Drug: Copegus; 1000/1200mg po daily for 24 weeks; Drug: Pegasys; 180 micrograms sc weekly for 24 weeks; Drug: Pegasys; 90 micrograms sc weekly for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sustained virological response (SVR)	24 weeks post treatment end (ie weeks 48 or 72)

Secondary Outcome Measures

Outcome Measure	Time Frame
Virological response over time	Throughout study
SVR	12 weeks post treatment end (ie weeks 36 or 60)
Relapse rate	End of treatment (ie weeks 24 or 48)
Adverse events (AEs), laboratory parameters.	Throughout treatment

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Nelson DR, Zeuzem S, Andreone P, Ferenci P, Herring R, Jensen DM, Marcellin P, Pockros PJ, Rodriguez-Torres M, Rossaro L, Rustgi VK, Sepe T, Sulkowski M, Thomason IR, Yoshida EM, Chan A, Hill G. Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients. Ann Hepatol. 2012 Jan-Feb;11(1):15-31.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: August 16, 2007
• First Submitted That Met QC Criteria: August 16, 2007
• First Posted (Estimate): August 17, 2007

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Immunologic Factors; Interferon-alpha; Peginterferon alfa-2a
• Other Study ID Numbers: NV19865

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No