search
Back to results

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

Primary Purpose

Hepatitis C, Chronic

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
RO5024048
RO5190591
RO5466731
ribavirin [Copegus]
ritonavir
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C, Chronic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

A: GT1a 3DAA

B: GT1a 3DAA

C: GT1a 2DAA

D: GT1b 3DAA

E: GT1b 2DAA

Part II

Arm Description

including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048

including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048

including RO5466731, RO5190591, ritonavir and ribavirin [Copegus]

including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048

including RO54664731, RO5190591, ritonavir and ribavirin [Copegus]

Outcomes

Primary Outcome Measures

Sustained virological response (defined as undetectable serum HCV RNA) 12 weeks after end of treatment
Safety: Incidence of adverse events

Secondary Outcome Measures

Antiviral activity: Change in serum HCV RNA levels
Pharmacokinetics in coadministration: Area under the concentration-time curve (AUC)
HCV drug resistance
Quality of life: Short-Form 36v2/Brief Fatigue Inventory questionnaires

Full Information

First Posted
June 22, 2012
Last Updated
November 1, 2016
Sponsor
Hoffmann-La Roche
search

1. Study Identification

Unique Protocol Identification Number
NCT01628094
Brief Title
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

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
110 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A: GT1a 3DAA
Arm Type
Experimental
Arm Description
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
Arm Title
B: GT1a 3DAA
Arm Type
Experimental
Arm Description
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
Arm Title
C: GT1a 2DAA
Arm Type
Experimental
Arm Description
including RO5466731, RO5190591, ritonavir and ribavirin [Copegus]
Arm Title
D: GT1b 3DAA
Arm Type
Experimental
Arm Description
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
Arm Title
E: GT1b 2DAA
Arm Type
Experimental
Arm Description
including RO54664731, RO5190591, ritonavir and ribavirin [Copegus]
Arm Title
Part II
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
RO5024048
Intervention Type
Drug
Intervention Name(s)
RO5190591
Intervention Type
Drug
Intervention Name(s)
RO5466731
Intervention Type
Drug
Intervention Name(s)
ribavirin [Copegus]
Intervention Type
Drug
Intervention Name(s)
ritonavir
Primary Outcome Measure Information:
Title
Sustained virological response (defined as undetectable serum HCV RNA) 12 weeks after end of treatment
Time Frame
approximately 20 months
Title
Safety: Incidence of adverse events
Time Frame
approximately 20 months
Secondary Outcome Measure Information:
Title
Antiviral activity: Change in serum HCV RNA levels
Time Frame
from baseline to 24 weeks after end of treatment
Title
Pharmacokinetics in coadministration: Area under the concentration-time curve (AUC)
Time Frame
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
Title
HCV drug resistance
Time Frame
approximately 20 months
Title
Quality of life: Short-Form 36v2/Brief Fatigue Inventory questionnaires
Time Frame
approximately 20 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
LaJolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
City
Saint Louise
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78234
Country
United States
City
Vancouver
State/Province
Washington
ZIP/Postal Code
98664
Country
United States
City
Kingswood
State/Province
New South Wales
Country
Australia
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
City
Berlin
ZIP/Postal Code
13353
Country
Germany
City
Frankfurt Am Main
ZIP/Postal Code
60590
Country
Germany
City
Hamburg
ZIP/Postal Code
20099
Country
Germany
City
Hannover
ZIP/Postal Code
30625
Country
Germany
City
Dunedin
ZIP/Postal Code
9016
Country
New Zealand
City
Grafton
ZIP/Postal Code
1010
Country
New Zealand
City
Hamilton
Country
New Zealand
City
Bialystok
ZIP/Postal Code
15-540
Country
Poland
City
Chorzow
ZIP/Postal Code
41-500
Country
Poland
City
Lodz
ZIP/Postal Code
91-357
Country
Poland
City
Myslowice
ZIP/Postal Code
41-400
Country
Poland

12. IPD Sharing Statement

Citations:
PubMed Identifier
26519669
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs