ANNAPURNA: A Study of The Combination of RO5466731, RO5190591, Ritonavir and Copegus (Ribavirin) With or Without RO5024048 in Patients With Chronic Hepatitis C Who Are Either Treatment-Naïve or Have Previously Experienced a Null Response to Interferon-Based Treatment

Phase 2

Completed

• Conditions: Hepatitis C, Chronic
• Interventions: Drug: RO5024048; Drug: RO5190591; Drug: RO5466731; Drug: ribavirin [Copegus]; Drug: ritonavir

• Registration Number: NCT01628094
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This randomized, open-label, multicenter study will evaluate the safety , efficacy and tolerability of the combination treatment RO5466731, RO5190591, ritonavir and Copegus (ribavirin) with or without RO5024048 in patients with chronic hepatitis C genotype 1. In Part 1, treatment-naïve patients will be randomized to receive treatment with RO5466731, RO5190591 plus ritonavir, and Copegus, with or without RO5024048. In Part 2, further treatment-naïve patients will receive a successful regimen from Part 1, or a reduced intensity regimen, and patients who have previously experienced null response to interferon-based treatment will be added to the study.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-06
• Study First Submitted: 2012-06-22
• Study First Submitted QC: 2012-06-22
• Study First Posted: 2012-06-26
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Disposition First Submitted: 2016-06-30
• Disposition First Submitted QC: 2016-07-01
• Disposition First Posted: 2016-07-04
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

• Adult patients, >/= 18 years of age
• Chronic hepatitis C genotype 1 of >/= 6 months duration at screening
• Part 1 and Part 2: Naïve to treatment with interferon (pegylated or non-pegylated). Patients who have participated in studies investigating a direct-acting antiviral agent with or without interferon are excluded
• Part 2: Treatment experienced patients having a previous null response to treatment with interferon containing regimen
• Liver biopsy or non-invasive (e.g. Fibroscan) evaluation in the past 24 calendar months showing absence of cirrhosis or incomplete/transition to cirrhosis
• Body mass index (BMI) 18 to 35 kg/m2 inclusive and body weight >/= 45 kg

Exclusion Criteria

• Pregnant or lactating women or males with female partners who are pregnant or lactating
• Decompensated liver disease or impaired liver function (as defined by protocol)
• Cirrhosis or incomplete/transition to cirrhosis
• Non- hepatitis C chronic liver disease
• Positive for hepatitis B or HIV infection
• History of pre-existing renal disease
• History of severe cardiac disease
• History of neoplastic disease within the last 5 years, except for localized or in situ carcinoma of the skin
• History of drug abuse within the last year; history of cannabinoid use is not excluded
• Evidence of alcohol abuse within 1 year of screening and consumption of more than 2 units of alcohol per day
• Medical condition that requires use of systemic corticosteroids
• Received warfarin or other anticoagulants during the 21 days immediately prior to screening or is expected to require warfarin or other anticoagulants during the study
• Anticipated use or need for significant medical treatment during the study or use of concomitant medications or nutrients that are excluded by protocol (e.g. drugs that are contraindicated with ritonavir, hormonal methods of contraception)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A: GT1a 3DAA	RO5024048	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
A: GT1a 3DAA	RO5190591	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
A: GT1a 3DAA	RO5466731	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
A: GT1a 3DAA	ribavirin [Copegus]	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
A: GT1a 3DAA	ritonavir	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
B: GT1a 3DAA	RO5024048	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
B: GT1a 3DAA	RO5190591	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
B: GT1a 3DAA	RO5466731	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
B: GT1a 3DAA	ribavirin [Copegus]	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
B: GT1a 3DAA	ritonavir	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
C: GT1a 2DAA	RO5190591	including RO5466731, RO5190591, ritonavir and ribavirin \[Copegus\]
C: GT1a 2DAA	RO5466731	including RO5466731, RO5190591, ritonavir and ribavirin \[Copegus\]
C: GT1a 2DAA	ribavirin [Copegus]	including RO5466731, RO5190591, ritonavir and ribavirin \[Copegus\]
C: GT1a 2DAA	ritonavir	including RO5466731, RO5190591, ritonavir and ribavirin \[Copegus\]
D: GT1b 3DAA	RO5024048	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
D: GT1b 3DAA	RO5190591	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
D: GT1b 3DAA	RO5466731	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
D: GT1b 3DAA	ribavirin [Copegus]	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
D: GT1b 3DAA	ritonavir	including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048
E: GT1b 2DAA	RO5190591	including RO54664731, RO5190591, ritonavir and ribavirin \[Copegus\]
E: GT1b 2DAA	RO5466731	including RO54664731, RO5190591, ritonavir and ribavirin \[Copegus\]
E: GT1b 2DAA	ribavirin [Copegus]	including RO54664731, RO5190591, ritonavir and ribavirin \[Copegus\]
E: GT1b 2DAA	ritonavir	including RO54664731, RO5190591, ritonavir and ribavirin \[Copegus\]
Part II	RO5024048	-
Part II	RO5190591	-
Part II	RO5466731	-
Part II	ribavirin [Copegus]	-
Part II	ritonavir	-

Primary Outcome Measures

Name	Time	Method
Sustained virological response (defined as undetectable serum HCV RNA) 12 weeks after end of treatment	approximately 20 months
Safety: Incidence of adverse events	approximately 20 months

Secondary Outcome Measures

Name	Time	Method
Antiviral activity: Change in serum HCV RNA levels	from baseline to 24 weeks after end of treatment
Pharmacokinetics in coadministration: Area under the concentration-time curve (AUC)	Pre-dose Weeks 1, 2, 3, 4, 6, 10, and 12 and up to 12 hours post-dose Weeks 1, and 4 or 3 and 6
Quality of life: Short-Form 36v2/Brief Fatigue Inventory questionnaires	approximately 20 months
HCV drug resistance	approximately 20 months