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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/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
Sex
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
1/05/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2013
Sample size
Target
Accrual to date
Final
381
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/ct2/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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01331850