Clinical trial NCT01628094: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-06-26
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Sustained virological response (defined as undetectable serum HCV RNA) 12 weeks after end of treatment
timeFrame: approximately 20 months
measure: Safety: Incidence of adverse events
timeFrame: approximately 20 months
Secondary outcomes:
measure: Antiviral activity: Change in serum HCV RNA levels
timeFrame: from baseline to 24 weeks after end of treatment
measure: Pharmacokinetics in coadministration: Area under the concentration-time curve (AUC)
timeFrame: 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
measure: HCV drug resistance
timeFrame: approximately 20 months
measure: Quality of life: Short-Form 36v2/Brief Fatigue Inventory questionnaires
timeFrame: approximately 20 months
Other outcomes:
Locations:
city: LaJolla
country: United States
state: California
city: Englewood
country: United States
state: Colorado
city: South Miami
country: United States
state: Florida
city: Marietta
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Chicago
country: United States
state: Illinois
city: Kansas City
country: United States
state: Kansas
city: Detroit
country: United States
state: Michigan
city: Saint Louise
country: United States
state: Missouri
city: Asheville
country: United States
state: North Carolina
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Vancouver
country: United States
state: Washington
city: Kingswood
country: Australia
state: New South Wales
city: Sydney
country: Australia
state: New South Wales
city: Westmead
country: Australia
state: New South Wales
city: Herston
country: Australia
state: Queensland
city: Parkville
country: Australia
state: Victoria
city: Berlin
country: Germany
city: Frankfurt Am Main
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Dunedin
country: New Zealand
city: Grafton
country: New Zealand
city: Hamilton
country: New Zealand
city: Bialystok
country: Poland
city: Chorzow
country: Poland
city: Lodz
country: Poland
city: Myslowice
country: Poland
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Jensen DM, Brunda M, Elston R, Gane EJ, George J, Glavini K, Hammond JM, Le Pogam S, Najera I, Passe S, Piekarska A, Rodriguez I, Zeuzem S, Chu T; ANNAPURNA study investigators. Interferon-free regimens containing setrobuvir for patients with genotype 1 chronic hepatitis C: a randomized, multicenter study. Liver Int. 2016 Apr;36(4):505-14. doi: 10.1111/liv.12997. Epub 2015 Dec 12.