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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01331850




Registration number
NCT01331850
Ethics application status
Date submitted
28/03/2011
Date registered
8/04/2011
Date last updated
2/11/2016

Titles & IDs
Public title
A Study of Danoprevir/Ritonavir and Copegus With RO5024048 and/or Pegasys in Patients With Chronic Hepatitis C
Scientific title
A Randomized Open-label Study to Evaluate the Sustained Virologic Response of Danoprevir/Ritonavir and Copegus in Combination With RO5024048 and/or Pegasys in Chronic Hepatitis C Genotype 1 Patients Who Failed Previous Standard Therapy
Secondary ID [1] 0 0
2010-019585-90
Secondary ID [2] 0 0
WV21913
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
Treatment: Drugs - Copegus
Treatment: Drugs - Copegus
Treatment: Drugs - Pegasys
Treatment: Drugs - Pegasys
Treatment: Drugs - RO5024048
Treatment: Drugs - danoprevir
Treatment: Drugs - ritonavir

Experimental: Previous null responders (Cohort B): Group 4 - Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. In addition, Group 4 will receive RO5024048 1000 mg twice a day and Copegus 1000 mg or 1200 mg twice a day for 24 weeks.

Experimental: Previous null responders (Cohort B): Group 5 - Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. Group 5 will receive RO5024048 1000 mg twice a day, Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks.

Experimental: Previous null responders (Cohort B): Group 6 - Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. Group 6 will receive RO5024048 1000 mg twice a day, Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks. In addition, patients in Group 6 will receive another 24 weeks of Pegasys plus Copegus treatment.

Experimental: Previous partial responders (Cohort A): Group 1 - Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. In addition, Group 1 will receive RO5024048 1000 mg twice a day and Copegus 1000 mg or 1200 mg twice a day for 24 weeks.

Experimental: Previous partial responders (Cohort A): Group 2 - Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. In addition, Group 2 will receive Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks.

Experimental: Previous partial responders (Cohort A): Group 3 - Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. Group 3 will receive RO5024048 1000 mg twice a day, Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks.


Treatment: Drugs: Copegus
1000 mg or 1200 mg daily oral doses for 24 weeks

Treatment: Drugs: Copegus
1000 mg or 1200 mg daily oral doses for 48 weeks

Treatment: Drugs: Pegasys
180 microgram subcutaneously once weekly for 24 weeks

Treatment: Drugs: Pegasys
180 microgram subcutaneously once weekly for 48 weeks

Treatment: Drugs: RO5024048
1000 mg oral doses twice a day for 24 weeks

Treatment: Drugs: danoprevir
100 mg oral doses twice a day for 24 weeks

Treatment: Drugs: ritonavir
100 mg oral doses twice a day for 24 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Sustained virological response (SVR) of danoprevir/ritonavir with RO5024048 and Copegus in patients with previous partial or null response to peginterferon/ribavirin treatment
Timepoint [1] 0 0
24 weeks
Primary outcome [2] 0 0
Sustained virological response (SVR) of danoprevir/ritonavir with Pegasys and Copegus in patients with previous partial response to peginterferon/ribavirin treatment
Timepoint [2] 0 0
24 weeks
Primary outcome [3] 0 0
Sustained virological response (SVR) of danoprevir/ritonavir and RO5024048 with Pegasys and Copegus in patients with previous partial or null response to peginterferon/ribavirin treatment
Timepoint [3] 0 0
24 weeks
Primary outcome [4] 0 0
Sustained virological response (SVR) of danoprevir/ritonavir and RO5024048 with Pegasys and Copegus followed by 24 weeks of Pegasys and Copegus treatment in patients with previous null response to peginterferon/ribavirin treatment
Timepoint [4] 0 0
48 weeks
Secondary outcome [1] 0 0
Safety (Incidence of adverse events) of danoprevir, RO5024048 and Copegus
Timepoint [1] 0 0
48 weeks
Secondary outcome [2] 0 0
Safety (Incidence of adverse events) of danoprevir, Pegasys and Copegus
Timepoint [2] 0 0
48 weeks
Secondary outcome [3] 0 0
Safety (Incidence of adverse events) of danoprevir, RO5024048, Pegasys and Copegus
Timepoint [3] 0 0
72 weeks
Secondary outcome [4] 0 0
Virological response over time
Timepoint [4] 0 0
48 weeks
Secondary outcome [5] 0 0
Change in danoprevir plasma concentration
Timepoint [5] 0 0
24 weeks
Secondary outcome [6] 0 0
Change in RO5024048 plasma concentration
Timepoint [6] 0 0
24 weeks
Secondary outcome [7] 0 0
Hepatitis C virus drug resistance profile
Timepoint [7] 0 0
24 weeks

Eligibility
Key inclusion criteria
- Adult patients, age 18 years and older

- Presence of hepatitis C infection, genotype 1a or 1b

- Documentation of previous treatment failure after receiving approved doses of
peginterferon plus ribavirin for at least 12 weeks

- Patients must have discontinued prior hepatitis C treatment at least 12 weeks prior to
study start
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Infection with any hepatitis C genotype or subtype other than genotype 1a or 1b

- Patients with cirrhosis

- Patients who were discontinued from previous peginterferon plus ribavirin therapy due
to reasons other than insufficient therapeutic response

- Co-infection with hepatitis B or human immunodeficiency virus (HIV)

- History or evidence of chronic liver disease other than hepatitis C

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
- Darlinghurst
Recruitment hospital [2] 0 0
- Kingswood
Recruitment hospital [3] 0 0
- Westmead
Recruitment hospital [4] 0 0
- Adelaide
Recruitment hospital [5] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2747 - Kingswood
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
3186 - Melbourne
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
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Oregon
Country [11] 0 0
United States of America
State/province [11] 0 0
Rhode Island
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
Austria
State/province [14] 0 0
Wien
Country [15] 0 0
Brazil
State/province [15] 0 0
RS
Country [16] 0 0
Brazil
State/province [16] 0 0
SP
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
British Columbia
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
France
State/province [20] 0 0
La Tronche
Country [21] 0 0
France
State/province [21] 0 0
Paris
Country [22] 0 0
France
State/province [22] 0 0
Pessac
Country [23] 0 0
France
State/province [23] 0 0
Vandoeuvre-les-nancy
Country [24] 0 0
Germany
State/province [24] 0 0
Berlin
Country [25] 0 0
Germany
State/province [25] 0 0
Essen
Country [26] 0 0
Germany
State/province [26] 0 0
Kiel
Country [27] 0 0
Germany
State/province [27] 0 0
Tübingen
Country [28] 0 0
Italy
State/province [28] 0 0
Campania
Country [29] 0 0
Italy
State/province [29] 0 0
Lombardia
Country [30] 0 0
Italy
State/province [30] 0 0
Toscana
Country [31] 0 0
Mexico
State/province [31] 0 0
Guadalajara
Country [32] 0 0
Poland
State/province [32] 0 0
Bydgoszcz
Country [33] 0 0
Poland
State/province [33] 0 0
Czeladz
Country [34] 0 0
Poland
State/province [34] 0 0
Kielce
Country [35] 0 0
Poland
State/province [35] 0 0
Warszawa
Country [36] 0 0
Poland
State/province [36] 0 0
Lodz
Country [37] 0 0
Puerto Rico
State/province [37] 0 0
San Juan
Country [38] 0 0
Spain
State/province [38] 0 0
Barcelona
Country [39] 0 0
Spain
State/province [39] 0 0
Madrid
Country [40] 0 0
Spain
State/province [40] 0 0
Sevilla
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Birmingham
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Dundee
Country [43] 0 0
United Kingdom
State/province [43] 0 0
London
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Manchester

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, multi-center study will evaluate the sustained virological
response, pharmacokinetics and safety of various combinations of danoprevir/ritonavir with
Copegus plus RO5024048 and/or Pegasys in patients with chronic hepatitis C infection.
Patients will be divided into 2 separate cohorts. Cohort A, previous partial responders, will
be randomized to Groups 1-3 and cohort B, previous null responders, will be randomized to
Groups 4-6. Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir
100 mg twice a day for 24 weeks. In addition, Groups 1 and 4 will receive RO5024048 1000 mg
twice a day and Copegus 1000 mg or 1200 mg twice a day for 24 weeks; Group 2 will receive
Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day
for 24 weeks; Groups 3, 5 and 6 will receive RO5024048 1000 mg twice a day, Pegasys 180
microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks.
In addition, patients in Group 6 will receive another 24 weeks of Pegasys plus Copegus
treatment.
Trial website
https://clinicaltrials.gov/show/NCT01331850
Trial related presentations / publications
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
Other publications