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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01628094




Registration number
NCT01628094
Ethics application status
Date submitted
22/06/2012
Date registered
26/06/2012
Date last updated
2/11/2016

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
2012-000638-21
Secondary ID [2] 0 0
NP28266
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: A: GT1a 3DAA - including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048

Experimental: B: GT1a 3DAA - including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048

Experimental: C: GT1a 2DAA - including RO5466731, RO5190591, ritonavir and ribavirin \[Copegus\]

Experimental: D: GT1b 3DAA - including RO5466731, RO5190591, ritonavir, ribavirin \[Copegus\] and RO5024048

Experimental: E: GT1b 2DAA - including RO54664731, RO5190591, ritonavir and ribavirin \[Copegus\]

Experimental: Part II -

Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Sustained virological response (defined as undetectable serum HCV RNA) 12 weeks after end of treatment
Timepoint [1] 0 0
approximately 20 months
Primary outcome [2] 0 0
Safety: Incidence of adverse events
Timepoint [2] 0 0
approximately 20 months
Secondary outcome [1] 0 0
Antiviral activity: Change in serum HCV RNA levels
Timepoint [1] 0 0
from baseline to 24 weeks after end of treatment
Secondary outcome [2] 0 0
Pharmacokinetics in coadministration: Area under the concentration-time curve (AUC)
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
HCV drug resistance
Timepoint [3] 0 0
approximately 20 months
Secondary outcome [4] 0 0
Quality of life: Short-Form 36v2/Brief Fatigue Inventory questionnaires
Timepoint [4] 0 0
approximately 20 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2013
Sample size
Target
Accrual to date
Final
110
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
- Kingswood
Recruitment hospital [2] 0 0
- Sydney
Recruitment hospital [3] 0 0
- Westmead
Recruitment hospital [4] 0 0
- Herston
Recruitment hospital [5] 0 0
- Parkville
Recruitment postcode(s) [1] 0 0
- Kingswood
Recruitment postcode(s) [2] 0 0
2050 - Sydney
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Hawaii
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Germany
State/province [14] 0 0
Frankfurt Am Main
Country [15] 0 0
Germany
State/province [15] 0 0
Hamburg
Country [16] 0 0
Germany
State/province [16] 0 0
Hannover
Country [17] 0 0
New Zealand
State/province [17] 0 0
Dunedin
Country [18] 0 0
New Zealand
State/province [18] 0 0
Grafton
Country [19] 0 0
New Zealand
State/province [19] 0 0
Hamilton
Country [20] 0 0
Poland
State/province [20] 0 0
Bialystok
Country [21] 0 0
Poland
State/province [21] 0 0
Chorzow
Country [22] 0 0
Poland
State/province [22] 0 0
Lodz
Country [23] 0 0
Poland
State/province [23] 0 0
Myslowice

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01628094
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01628094