A Study of RO5024048 in Combination With Pegasys and Copegus in Treatment-Naive Patients With Chronic Hepatitis C, Genotype 1 or 4

A Randomized, Double-blind, Multicenter, Dose and Duration Finding Study to Evaluate the Sustained Virologic Response of the HCV Polymerase Inhibitor Prodrug (RO5024048) in Combination With Pegasys® and Ribavirin® (SOC) Versus SOC in Treatment-Naïve Patients With HCV Genotype 1 or 4 Infection

This 6-arm study will assess the efficacy and safety of RO5024048 (R7128) in combination with the approved doses of Pegasys (180micrograms sc weekly) + Copegus (1000/1200mg po daily) (SOC), versus SOC in treatment-naive patients with chronic hepatitis C, genotype 1 and 4. The first 3 groups will receive 1) RO5024048 500mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks; 2)RO5024048 1000mg bid + Pegasys + Copegus for 8 weeks, followed by SOC for 16 weeks; 3) RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks. After 24 weeks, patients in these 3 groups who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks. Group 4 will receive RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 36 weeks, and group 5 will receive SOC for 48 weeks. Group 6 provides retreatment on an open-label basis for patients of Group 5 who failed treatment. Patients will receive RO5024048 1000mg bid + Pegasys + Copegus for 24 weeks, followed by SOC for 24 weeks. The anticipated time on study treatment is 6-12 months.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: Copegus; Drug: Copegus; Drug: Pegasys; Drug: Pegasys; Drug: RO5024048; Drug: RO5024048; Drug: RO5024048; Drug: RO5024048

• Study Type: Interventional
• Enrollment (Actual): 413
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2050
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
    • Herston, Queensland, Australia, 4006
    • Woolloongabba, Queensland, Australia, 4102
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
    • Melbourne, Victoria, Australia, 3004
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
    • Perth, Western Australia, Australia, 6001
• Austria
  • Wien, Austria, 1090
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
    • Edmonton, Alberta, Canada, T6G 2B7
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
    • Vancouver, British Columbia, Canada, V6Z 2K5
  • Ontario
    • London, Ontario, Canada, N6A 5A5
    • Toronto, Ontario, Canada, M5G 1L7
  • Quebec
    • Montreal, Quebec, Canada, H2X 3J4
• France
  • Creteil, France, 94010
  • La Tronche, France, 38700
  • Lille, France, 59037
  • Nice, France, 06202
  • Paris, France, 75651
  • Paris, France, 75679
  • Pessac, France, 33604
  • Vandoeuvre-les-nancy, France, 54511
• Germany
  • Berlin, Germany, 13353
  • Frankfurt Am Main, Germany, 60590
  • Freiburg, Germany, 79106
  • Hannover, Germany, 30625
  • Muenchen, Germany, 81377
  • Ulm, Germany, 89081
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
  • Lombardia
    • Milano, Lombardia, Italy, 20121
  • Piemonte
    • Torino, Piemonte, Italy, 10126
  • Toscana
    • Pisa, Toscana, Italy, 56124
• Puerto Rico
  • Santurce, Puerto Rico, 00909
• Spain
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08003
  • Granada, Spain, 18003
  • Madrid, Spain, 28222
  • Sevilla, Spain, 41014
  • Valencia, Spain, 46014
  • Barcelona
    • Badalona, Barcelona, Spain, 08915
  • La Coruña
    • La Coruna, La Coruña, Spain, 15006
• United Kingdom
  • London, United Kingdom, SE5 9RS
  • London, United Kingdom, W1 1TF
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
  • California
    • La Jolla, California, United States, 92037-1030
    • Sacramento, California, United States, 95817
    • San Diego, California, United States, 92103-8465
    • San Francisco, California, United States, 94115
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
  • Florida
    • Bradenton, Florida, United States, 34209
    • Gainesville, Florida, United States, 32610-0214
  • Georgia
    • Marietta, Georgia, United States, 30060
  • Illinois
    • Chicago, Illinois, United States, 60637
  • Maryland
    • Lutherville, Maryland, United States, 21093
  • Missouri
    • Kansas City, Missouri, United States, 64131
  • New Jersey
    • Newark, New Jersey, United States, 07102
  • New York
    • New York, New York, United States, 10021
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
  • South Carolina
    • Columbia, South Carolina, United States, 29204
  • Tennessee
    • Nashville, Tennessee, United States, 37211
  • Texas
    • Houston, Texas, United States, 77030
    • San Antonio, Texas, United States, 78234
  • Virginia
    • 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 or 4
• Treatment-naive

Exclusion Criteria:

• No previous treatment with any interferon- or ribavirin-based therapy
• Other forms of liver disease
• HIV infection

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; RO5024048 500 mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks.	Drug: Copegus; 1000/1200mg po daily for 24 or 48 weeks; Drug: Copegus; 1000/1200mg po daily for 48 weeks; Drug: Pegasys; 180 micrograms sc weekly for 24 or 48 weeks; Drug: Pegasys; 180 micrograms sc weekly for 48 weeks; Drug: RO5024048; 1000mg bid for 24 weeks; Drug: RO5024048; 500mg bid for 12 weeks; Drug: RO5024048; 1000mg bid for 8 weeks; Drug: RO5024048; 1000mg bid for 12 weeks
Experimental: Group 2; RO5024048 1000mg bid + Pegasys + Copegus for 8 weeks, followed by SOC for 16 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks.	Drug: Copegus; 1000/1200mg po daily for 24 or 48 weeks; Drug: Copegus; 1000/1200mg po daily for 48 weeks; Drug: Pegasys; 180 micrograms sc weekly for 24 or 48 weeks; Drug: Pegasys; 180 micrograms sc weekly for 48 weeks; Drug: RO5024048; 1000mg bid for 24 weeks; Drug: RO5024048; 500mg bid for 12 weeks; Drug: RO5024048; 1000mg bid for 8 weeks; Drug: RO5024048; 1000mg bid for 12 weeks
Experimental: Group 3; RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 12 weeks. After 24 weeks, patients who have achieved rapid viral response will stop treatment, and those who have not will receive SOC for a further 24 weeks.	Drug: Copegus; 1000/1200mg po daily for 24 or 48 weeks; Drug: Copegus; 1000/1200mg po daily for 48 weeks; Drug: Pegasys; 180 micrograms sc weekly for 24 or 48 weeks; Drug: Pegasys; 180 micrograms sc weekly for 48 weeks; Drug: RO5024048; 1000mg bid for 24 weeks; Drug: RO5024048; 500mg bid for 12 weeks; Drug: RO5024048; 1000mg bid for 8 weeks; Drug: RO5024048; 1000mg bid for 12 weeks
Experimental: Group 4; Group 4 will receive RO5024048 1000mg bid + Pegasys + Copegus for 12 weeks, followed by SOC for 36 weeks	Drug: Copegus; 1000/1200mg po daily for 24 or 48 weeks; Drug: Copegus; 1000/1200mg po daily for 48 weeks; Drug: Pegasys; 180 micrograms sc weekly for 24 or 48 weeks; Drug: Pegasys; 180 micrograms sc weekly for 48 weeks; Drug: RO5024048; 1000mg bid for 24 weeks; Drug: RO5024048; 500mg bid for 12 weeks; Drug: RO5024048; 1000mg bid for 8 weeks; Drug: RO5024048; 1000mg bid for 12 weeks
Active Comparator: Group 5; Group 5 will receive SOC for 48 weeks	Drug: Copegus; 1000/1200mg po daily for 24 or 48 weeks; Drug: Copegus; 1000/1200mg po daily for 48 weeks; Drug: Pegasys; 180 micrograms sc weekly for 24 or 48 weeks; Drug: Pegasys; 180 micrograms sc weekly for 48 weeks
Experimental: Group 6; Group 6 provides retreatment on an open-label basis for patients of Group 5 who failed treatment. Patients will receive RO5024048 1000mg bid + Pegasys + Copegus for 24 weeks, followed by SOC for 24 weeks.	Drug: Copegus; 1000/1200mg po daily for 24 or 48 weeks; Drug: Copegus; 1000/1200mg po daily for 48 weeks; Drug: Pegasys; 180 micrograms sc weekly for 24 or 48 weeks; Drug: Pegasys; 180 micrograms sc weekly for 48 weeks; Drug: RO5024048; 1000mg bid for 24 weeks; Drug: RO5024048; 500mg bid for 12 weeks; Drug: RO5024048; 1000mg bid for 8 weeks; Drug: RO5024048; 1000mg bid for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sustained virologic response: Percentage of patients with undetectable Hepatitis C RNA level	24 weeks after end of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Virologic response: Percentage of patients with undetectable Hepatitis C RNA level	60 Weeks
Virologic response: Percentage of patients with undetectable Hepatitis C RNA level	12 weeks post-treatment
Relapse rate: Percentage of patients who achieved a virologic response at the end of treatment but had detectable Hepatitis C RNA level at the last assessment post treatment	72 weeks
Safety: Incidence of adverse events	72 weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Tong X, Le Pogam S, Li L, Haines K, Piso K, Baronas V, Yan JM, So SS, Klumpp K, Najera I. In vivo emergence of a novel mutant L159F/L320F in the NS5B polymerase confers low-level resistance to the HCV polymerase inhibitors mericitabine and sofosbuvir. J Infect Dis. 2014 Mar 1;209(5):668-75. doi: 10.1093/infdis/jit562. Epub 2013 Oct 23.

Study record dates

Study Major Dates

• Study Start: February 1, 2001
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: March 25, 2009
• First Submitted That Met QC Criteria: March 25, 2009
• First Posted (Estimate): March 26, 2009

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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Immunologic Factors; Interferon-alpha; Ribavirin; Peginterferon alfa-2a
• Other Study ID Numbers: NV20536; 2008-008258-21