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.

Phase 2

Completed

• Conditions: Hepatitis C, Chronic
• Interventions: Drug: Copegus; Drug: Pegasys; Drug: RO4588161

• Registration Number: NCT00517439
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2007-08-16
• Study First Submitted QC: 2007-08-16
• Study First Posted: 2007-08-17
• Study Start: 2007-12
• Primary Completion: 2010-01
• Study Completion: 2010-01
• Disposition First Submitted: 2016-07-07
• Disposition First Submitted QC: 2016-07-08
• Disposition First Posted: 2016-07-12
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 516

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 4	Pegasys	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).
Group 5	Pegasys	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).
Group 1	Pegasys	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).
Group 1	RO4588161	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).
Group 2	Pegasys	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).
Group 2	RO4588161	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).
Group 3	Pegasys	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 4	Copegus	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).
Group 4	RO4588161	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).
Group 5	Copegus	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).
Group 5	RO4588161	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).
Group 6	Pegasys	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).
Group 6	RO4588161	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).
Group 7	Copegus	Standard of care (SOC)
Group 7	Pegasys	Standard of care (SOC)
Group 3	Copegus	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 1	Copegus	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).
Group 2	Copegus	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).
Group 6	Copegus	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).
Group 3	RO4588161	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.

Primary Outcome Measures

Name	Time	Method
Sustained virological response (SVR)	24 weeks post treatment end (ie weeks 48 or 72)

Secondary Outcome Measures

Name	Time	Method
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