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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT01628094

Collaborator

(none)

110

Enrollment

Locations

Arms

Duration (Months)

3.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: RO5024048 Drug: RO5190591 Drug: RO5466731 Drug: ribavirin [Copegus] Drug: ritonavir	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized, Open-Label, Multicenter Study of Safety, Efficacy, and Tolerability of the Combination of RO5466731, RO5190591, Ritonavir, and Copegus With or Without RO5024048 in HCV Genotype 1 Infected Patients Who Are Either Treatment Naïve or Null Responders to Previous Interferon-Based Treatment

Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Nov 1, 2013

Actual Study Completion Date :

Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A: GT1a 3DAA including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048	Drug: RO5024048 Drug: RO5190591 Drug: RO5466731 Drug: ribavirin [Copegus] Drug: ritonavir
Experimental: B: GT1a 3DAA including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048	Drug: RO5024048 Drug: RO5190591 Drug: RO5466731 Drug: ribavirin [Copegus] Drug: ritonavir
Experimental: C: GT1a 2DAA including RO5466731, RO5190591, ritonavir and ribavirin [Copegus]	Drug: RO5190591 Drug: RO5466731 Drug: ribavirin [Copegus] Drug: ritonavir
Experimental: D: GT1b 3DAA including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048	Drug: RO5024048 Drug: RO5190591 Drug: RO5466731 Drug: ribavirin [Copegus] Drug: ritonavir
Experimental: E: GT1b 2DAA including RO54664731, RO5190591, ritonavir and ribavirin [Copegus]	Drug: RO5190591 Drug: RO5466731 Drug: ribavirin [Copegus] Drug: ritonavir
Experimental: Part II	Drug: RO5024048 Drug: RO5190591 Drug: RO5466731 Drug: ribavirin [Copegus] Drug: ritonavir

Outcome Measures

Primary Outcome Measures

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

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]
HCV drug resistance [approximately 20 months]
Quality of life: Short-Form 36v2/Brief Fatigue Inventory questionnaires [approximately 20 months]

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
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)

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	LaJolla	California	United States	92037
2	Englewood	Colorado	United States	80113
3	South Miami	Florida	United States	33143
4	Marietta	Georgia	United States	30060
5	Honolulu	Hawaii	United States	96813
6	Chicago	Illinois	United States	60637
7	Kansas City	Kansas	United States	66160
8	Detroit	Michigan	United States	48202
9	Saint Louise	Missouri	United States	63104
10	Asheville	North Carolina	United States	28801
11	Dallas	Texas	United States	75246
12	Houston	Texas	United States	77030
13	San Antonio	Texas	United States	78215
14	San Antonio	Texas	United States	78234
15	Vancouver	Washington	United States	98664
16	Kingswood	New South Wales	Australia
17	Sydney	New South Wales	Australia	2050
18	Westmead	New South Wales	Australia	2145
19	Herston	Queensland	Australia	4029
20	Parkville	Victoria	Australia	3052
21	Berlin		Germany	13353
22	Frankfurt Am Main		Germany	60590
23	Hamburg		Germany	20099
24	Hannover		Germany	30625
25	Dunedin		New Zealand	9016
26	Grafton		New Zealand	1010
27	Hamilton		New Zealand
28	Bialystok		Poland	15-540
29	Chorzow		Poland	41-500
30	Lodz		Poland	91-357
31	Myslowice		Poland	41-400