A Study of RO5024048 in Combination With Ritonavir-Boosted Danoprevir and Pegasys/Copegus in Patients With Chronic Hepatitis C Genotype 1 Who Have Failed Prior HCV Protease Inhibitor Treatment

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT01579019

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

This randomized, double blind, phase II study will evaluate the efficacy and safety of two doses of RO5024048 in combination with ritonavir-boosted danoprevir and Pegasys (peginterferon alpha-2a) and Copegus (ribavirin) in patients who failed a prior protease inhibitor containing regimen with or without pegylated interferon. Patients will be randomized to receive either a 2-week lead-in of RO5024048 (1500 mg or 1000 mg orally twice daily) in combination with Pegasys (180 mcg subcutaneously weekly) and Copegus (1000 mg or 1200 mg orally daily) followed by 24 weeks of therapy with RO5024048 in combination with danoprevir (100 mg orally twice daily) plus ritonavir (100 mg orally twice daily) and Pegasys and Copegus (QUAD therapy), or 24 weeks of therapy with RO5024048 in combination with danoprevir plus ritonavir and Pegasys and Copegus (QUAD therapy). Anticipated time on study treatment is 24 or 26 weeks, with a treatment-free follow-up of 24 weeks.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: RO5024048 Drug: RO5024048 Drug: danoprevir Drug: peginterferon alfa-2a [Pegasys] Drug: ribavirin [Copegus] Drug: ritonavir	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Study Start Date :

Jul 1, 2012

Anticipated Primary Completion Date :

Mar 1, 2014

Anticipated Study Completion Date :

Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1000 mg 24 weeks	Drug: RO5024048 1000 mg po bid, 24 or 26 weeks Drug: danoprevir 100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26 Drug: peginterferon alfa-2a [Pegasys] 180 mcg sc qw, 24 or 26 weeks Drug: ribavirin [Copegus] 1000 mg or 1200 mg po daily, 24 or 26 weeks
Active Comparator: 1000 mg 26 weeks	Drug: RO5024048 1000 mg po bid, 24 or 26 weeks Drug: danoprevir 100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26 Drug: peginterferon alfa-2a [Pegasys] 180 mcg sc qw, 24 or 26 weeks Drug: ribavirin [Copegus] 1000 mg or 1200 mg po daily, 24 or 26 weeks Drug: ritonavir 100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26
Experimental: 1500 mg 24 weeks	Drug: RO5024048 1500 mg po bid, 24 or 26 weeks Drug: danoprevir 100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26 Drug: peginterferon alfa-2a [Pegasys] 180 mcg sc qw, 24 or 26 weeks Drug: ribavirin [Copegus] 1000 mg or 1200 mg po daily, 24 or 26 weeks Drug: ritonavir 100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26
Experimental: 1500 mg 26 weeks	Drug: RO5024048 1500 mg po bid, 24 or 26 weeks Drug: danoprevir 100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26 Drug: peginterferon alfa-2a [Pegasys] 180 mcg sc qw, 24 or 26 weeks Drug: ribavirin [Copegus] 1000 mg or 1200 mg po daily, 24 or 26 weeks Drug: ritonavir 100 mg po bid, Weeks 1 to 24 or Weeks 3 to 26

Outcome Measures

Primary Outcome Measures

Sustained virologic response (defined as unquantifiable serum HCV RNA) 12 weeks after treatment (SVR-12) [approximately 2 years]

Secondary Outcome Measures

Sustained virologic response 4 weeks after treatment (SVR-4) [approximately 2 years]
Sustained virologic response 24 weeks after treatment (SVR-24) [approximately 2 years]
Change in serum HCV RNA levels [from baseline to Week 12]
Virologic response over time [from baseline to 24 weeks after treatment]
Correlation between trough concentrations of RO4995855 and virologic response [approximately 2 years]
Incidence of direct-acting antiviral (DAA) resistance, including re-emergence of protease inhibitor resistant virus [approximately 2 years]
Safety: Incidence of adverse events [approximately 2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients, >/= 18 years of age
Hepatitis C genotype 1 infection
Serum HCV quantifiable by Roche COBAS TaqMan HCV Test v2.0
Liver biopsy (within 24 months) or Fibroscan (within 12 months) before first administration of study drug consistent with chronic hepatitis C and demonstrating absence of liver cirrhosis
Documented failed prior treatment with protease inhibitor (evidenced by viral breakthrough or partial response while on treatment or relapse after treatment), including documentation on treatment with other direct-acting antiviral agents and other HCV antiviral treatment
Patients must have discontinued prior HCV treatment at least 24 weeks prior to first dose of study drug in this trial

Exclusion Criteria:

Infection with any HCV genotype other than genotype 1
Evidence of any variants associated with protease inhibitor resistance at screening
Body mass index (BMI) <18 or >/=36 kg/m2
Positive for hepatitis A or hepatitis B infection
Use of any systemic antiviral therapy with perceived activity against HCV </=1 month prior to first dose of study drug
History or evidence of a medical condition associated with chronic liver disease other than chronic hepatitis C
Pregnant or breastfeeding women
Males with female partners who are pregnant
History of immunologically mediated disease; patients with rheumatoid arthritis requiring only intermittent non-steroidal anti-inflammatory medications or with celiac disease will be allowed
History or evidence of decompensated liver disease
History or evidence of renal disease; patients with history of nephrolithiasis will be allowed
Uncontrolled Type 1 or 2 diabetes
History or evidence of chronic pulmonary disease associated with functional limitation
History of severe cardiac disease History of any neoplastic disease within the last 5 years, except for localized or in situ carcinoma of the skin (e.g. basal or squamous cell carcinoma)
Evidence of excessive alcohol, drug or substance abuse (excluding marijuana use) within 1 year of the first dose of study drug