A Study of Ritonavir-Boosted Danoprevir and RO5024048 in Different Combinations in Null Responder or Treatment-Naïve Patients With Chronic Hepatitis C and Compensated Cirrhosis

Tracking Information
First Submitted Date ICMJE	November 30, 2011
First Posted Date ICMJE	December 1, 2011
Last Update Posted Date	August 1, 2016
Study Start Date ICMJE	April 2012
Actual Primary Completion Date	September 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 20, 2016)	Safety: Incidence of adverse events [ Time Frame: 48 weeks ]; Pharmacokinetics (PK): Area under the concentration-time curve (AUC) [ Time Frame: Intensive PK sample collection during initial 2 week dosing period, followed by routine sampling during treatment up to Week 24 ]; Antiviral activity: Hepatitis C virus (HCV) RNA levels assessed by Roche COBAS Taqman HCV Test [ Time Frame: 48 weeks ]
Original Primary Outcome Measures ICMJE; (submitted: November 30, 2011)	Safety: Incidence of adverse events [ Time Frame: 48 weeks ]; Pharmacokinetics: Area under the concentration-time curve (AUC) [ Time Frame: Intensive PK sample collection during initial 2 week dosing period, followed by routine sampling during treatment up to Week 24 ]; Antiviral activity: HCV RNA levels assessed by Roche COBAS Taqman HCV Test [ Time Frame: 48 weeks ]
Change History	Complete list of historical versions of study NCT01483742 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 30, 2011)	Emergence of viral resistance: HCV RNA gene sequence variations [ Time Frame: From baseline to Week 48 ]; Virologic response: HCV RNA levels [ Time Frame: approximately 1 year ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Study of Ritonavir-Boosted Danoprevir and RO5024048 in Different Combinations in Null Responder or Treatment-Naïve Patients With Chronic Hepatitis C and Compensated Cirrhosis
Official Title ICMJE	A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Ritonavir-Boosted DANOPREVIR and RO5024048 in Different Combinations in Null Responder or Treatment Naïve Patients With Chronic Hepatitis C and Compensated Cirrhosis
Brief Summary	This open-label, parallel cohort study will evaluate the safety, pharmacokinetics and antiviral activity of ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients, and with RO5024048 added to the combination treatment in prior null responder patients with chronic hepatitis C genotype 1 or 4 and compensated cirrhosis. All patients will receive danoprevir 100 mg orally twice daily (bid) , ritonavir 100 mg orally bid, Pegasys 180 mcg subcutaneously weekly and ribavirin 1000-1200 mg/kg/day orally. Prior non-responders will receive RO5024048 1000 mg orally bid additionally. Anticipated time on study treatment is 24 weeks.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Hepatitis C, Chronic
Intervention ICMJE	Drug: RO5024048 1000 mg orally bid, 24 weeks; Drug: danoprevir 100 mg orally bid, 24 weeks; Drug: peginterferon alfa-2a [Pegasys] 180 mcg weekly, 24 weeks; Drug: ribavirin 1000-1200 mg/kg/day orally in two divided doses, 24 weeks; Drug: ritonavir 100 mg orally bid, 24 weeks
Study Arms	Experimental: Combination without RO5024048 Ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients Interventions: Drug: danoprevir Drug: peginterferon alfa-2a [Pegasys] Drug: ribavirin Drug: ritonavir; Experimental: Combination with RO5024048 RO5024048 added to the combination treatment (ritonavir-boosted danoprevir in combination with Pegasys [peginterferon alfa-2a] and ribavirin) in prior null responder patients Interventions: Drug: RO5024048 Drug: danoprevir Drug: peginterferon alfa-2a [Pegasys] Drug: ribavirin Drug: ritonavir
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: March 11, 2013)	43
Original Estimated Enrollment ICMJE; (submitted: November 30, 2011)	40
Actual Study Completion Date	September 2013
Actual Primary Completion Date	September 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Adult patients, 18 to 65 years of age inclusive; Chronic hepatitis C, genotype 1 or 4; Cohort 1: Treatment-naïve for hepatitis C; Cohort 2: Prior null responder to treatment with approved doses of pegylated interferon plus ribavirin; Liver biopsy confirming cirrhosis; Compensated cirrhosis (Child-Pugh A) Exclusion Criteria: Pregnant or lactating women or male partners of women who are pregnant; History or presence of decompensated liver disease (ascites, hepatic encephalopathy, hepatocellular carcinoma, or bleeding esophageal varices); Cohort 2: Patients who discontinued previous pegylated interferon plus ribavirin treatment due to reasons other than null response; History of clinically significant cardiovascular or cerebrovascular disease
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 65 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Australia, Canada, France, New Zealand, Poland, Slovakia, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01483742
Other Study ID Numbers ICMJE	NP27946; 2011-004129-28 ( EudraCT Number )
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Hoffmann-La Roche
Study Sponsor ICMJE	Hoffmann-La Roche
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Clinical Trials Hoffmann-La Roche
PRS Account	Hoffmann-La Roche
Verification Date	July 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP