Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01132313




Registration number
NCT01132313
Ethics application status
Date submitted
3/05/2010
Date registered
28/05/2010
Date last updated
1/02/2016

Titles & IDs
Public title
Safety, Antiviral Effect and PK of BI 207127 + BI 201335 +/- RBV for 4 up to 40 Weeks in Patients With Chronic HCV Genotype 1 Infection
Scientific title
Safety, Antiviral Effect and Pharmacokinetics of BI 207127 in Combination With BI 201335 and With or Without Ribavirin for 4, 16, 24, 28 or 40 Weeks in Patients With Chronic HCV Genotype 1 Infection (Randomized Phase Ib/II)
Secondary ID [1] 0 0
2009-018197-66
Secondary ID [2] 0 0
1241.21
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 - BI 207127
Treatment: Drugs - BI 201335
Treatment: Drugs - BI 207127
Treatment: Drugs - BI 201335
Treatment: Drugs - Ribavirin
Treatment: Drugs - Ribavirin
Treatment: Drugs - Ribavirin
Treatment: Drugs - BI 207127
Treatment: Drugs - BI 207127
Treatment: Drugs - BI 207127
Treatment: Drugs - BI 201335
Treatment: Drugs - Ribavirin
Treatment: Drugs - Ribavirin
Treatment: Drugs - BI 207127
Treatment: Drugs - BI 207127
Treatment: Drugs - BI 201335
Treatment: Drugs - BI 201335
Treatment: Drugs - Ribavirin
Treatment: Drugs - BI 201335
Treatment: Drugs - BI 201335
Treatment: Drugs - BI 207127
Treatment: Drugs - BI 201335
Treatment: Drugs - BI 201335
Treatment: Drugs - BI 207127
Treatment: Drugs - BI 201335
Treatment: Drugs - Ribavirin
Treatment: Drugs - Ribavirin
Treatment: Drugs - BI 207217
Treatment: Drugs - BI 201335
Treatment: Drugs - BI 207127
Treatment: Drugs - Ribavirin
Treatment: Drugs - BI 207127
Treatment: Drugs - BI 201335
Treatment: Drugs - Ribavirin
Treatment: Drugs - Ribavirin

Experimental: 2 - 4 weeks of high dose TID BI 207127 and QD BI 201335 in combination with RBV, Part 1

Experimental: 1 - 4 weeks of low dose three times per day (TID) BI 207127 and once daily (QD) BI 201335 in combination with RBV, Part 1

Experimental: 3 - 16 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2

Experimental: 4 - 28 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2

Experimental: 5 - 40 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2

Experimental: 6 - 28 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 2

Experimental: 7 - 28 weeks of TID BI 207127 and QD BI 201335 without RBV, Part 2

Experimental: 8 - 16 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 3

Experimental: 9 - 24 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 3

Experimental: 10 - 24 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 3

Experimental: 11 - 16 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 4

Experimental: 12 - 24 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 4


Treatment: Drugs: BI 207127
28 weeks, high dose, TID

Treatment: Drugs: BI 201335
40 weeks, QD

Treatment: Drugs: BI 207127
4 weeks, low dose TID

Treatment: Drugs: BI 201335
24 weeks, QD

Treatment: Drugs: Ribavirin
16 weeks, according to label

Treatment: Drugs: Ribavirin
28 weeks, according to label

Treatment: Drugs: Ribavirin
28 weeks, according to label

Treatment: Drugs: BI 207127
40 weeks, high dose, TID

Treatment: Drugs: BI 207127
24 weeks, very high dose, BID

Treatment: Drugs: BI 207127
16 weeks, standard dose, BID

Treatment: Drugs: BI 201335
24 weeks, QD

Treatment: Drugs: Ribavirin
48 weeks, according to label

Treatment: Drugs: Ribavirin
40 weeks, according to label

Treatment: Drugs: BI 207127
16 weeks, high dose, TID

Treatment: Drugs: BI 207127
28 weeks, high dose, TID

Treatment: Drugs: BI 201335
28 weeks, QD

Treatment: Drugs: BI 201335
16 weeks, QD

Treatment: Drugs: Ribavirin
24 weeks, according to label

Treatment: Drugs: BI 201335
24 weeks, QD

Treatment: Drugs: BI 201335
28 weeks, QD

Treatment: Drugs: BI 207127
24 weeks, standard dose, BID

Treatment: Drugs: BI 201335
24 weeks, QD

Treatment: Drugs: BI 201335
16 weeks, QD

Treatment: Drugs: BI 207127
16 weeks, high dose, BID

Treatment: Drugs: BI 201335
24 weeks, QD

Treatment: Drugs: Ribavirin
16 weeks, according to label

Treatment: Drugs: Ribavirin
16 weeks, according to label

Treatment: Drugs: BI 207217
28 weeks, high dose BID

Treatment: Drugs: BI 201335
16 weeks, QD

Treatment: Drugs: BI 207127
24 weeks, high dose, TID

Treatment: Drugs: Ribavirin
48 weeks, according to label

Treatment: Drugs: BI 207127
4 weeks, high dose, TID

Treatment: Drugs: BI 201335
28 weeks, QD

Treatment: Drugs: Ribavirin
24 weeks, according to label

Treatment: Drugs: Ribavirin
24 weeks, according to label
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Rapid Virological Response (RVR)
Timepoint [1] 0 0
4 weeks
Primary outcome [2] 0 0
Part 2: Sustained Virological Response (SVR)
Timepoint [2] 0 0
From drug administration until 12 weeks after end of treatment, up to 52 weeks
Primary outcome [3] 0 0
Part 3 and 4: Sustained Virological Response (SVR)
Timepoint [3] 0 0
From drug administration until 12 weeks after end of treatment, up to 36 weeks
Secondary outcome [1] 0 0
Part 1: Time to Virological Response
Timepoint [1] 0 0
From drug administration until end of drug administration, up to 4 weeks
Secondary outcome [2] 0 0
Part 2: Time to Virological Response
Timepoint [2] 0 0
From drug administration until end of drug administration, up to 40 weeks
Secondary outcome [3] 0 0
Part 1 and 2: Plasma HCV RNA Level Not Detectable at Week 4
Timepoint [3] 0 0
4 weeks
Secondary outcome [4] 0 0
Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment
Timepoint [4] 0 0
4 weeks and 24 weeks after the end of treatment, up to 64 weeks
Secondary outcome [5] 0 0
Part 3 and 4: Plasma HCV RNA Level <25 IU/mL at Week 4 and 12 of Treatment
Timepoint [5] 0 0
Week 4 and 12
Secondary outcome [6] 0 0
Part 3 and 4: Sustained Virological Response (SVR) at 4 Weeks After End of Treatment
Timepoint [6] 0 0
up to 28 weeks

Eligibility
Key inclusion criteria
Inclusion criteria:

- Chronic hepatitis C virus (HCV) infection of genotype (GT) 1

- Parts 1-3:Treatment naive to Interferon -alfa (IFN), Pegylated interferon -alfa
(PegIFN), ribavirin (RBV), and any direct acting antiviral agent for chronic hepatitis
C

- Part 4: Treatment experienced with confirmed prior virological failure to an approved
dose of PegIFN/RBV (null-response)

- HCV RNA >=10,000 IU/mL at screening

- Liver biopsy within two years or fibroscan within six months prior to baseline

- Liver biopsy within two years or fibroscan within 6 months prior to screening

- Age 18-75 years
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Hepatitis C virus (HCV) infection of mixed genotype

- Evidence of liver disease due to causes other than chronic HCV infection

- Positive ELISA for human immunodeficiency virus (HIV)

- Hepatitis B virus (HBV) infection

- Decompensated liver disease or history of decompensated liver disease

- Active or suspected malignancy within the last 5 years

- Ongoing or historical photosensitivity or recurrent rash

- History of alcohol or drug abuse (except cannabis) within the past 12 months

- Body mass index (BMI)I <18 or > 35 kg/m2

- Usage of any investigational drugs within 30 days prior to enrolment, or 5 half-lives,
whichever is longer; o the planned usage of an investigational drug during the course
of the current study

- Known hypersensitivity to any ingredient of the study drugs

- A condition that is defined as one which in the opinion of the investigator may
interfere with the patient's capability for participation in the trial or may
influence the results of the trial

- Alpha fetoprotein >100ng/mL at screening; if >20ng/mL and <=100ng/mL, patients can be
included if there is no evidence of liver cancer in an appropriate imaging study
within 6 months prior to randomisation

- Total bilirubin > 2 mg/dL with ratio of direct/indirect > 1

- AST or ALT >5xULN

- INR prolonged to >1.7xULN

- Requirement for chronic systemic corticosteroids

- Received concomitant systemic antiviral, hematopoietic growth factor, or
immunomodulatory treatment within 30 days prior to enrolment or 5 half-lives,
whichever is longer

- Received silymarin or glycyrrhizin or Sho-saiko-to within 30 days prior to enrolment

- Contraindications pertaining to PegIFN or RBV

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
1/05/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2014
Sample size
Target
Accrual to date
Final
488
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
1241.21.61002 Boehringer Ingelheim Investigational Site - Heidelberg
Recruitment hospital [2] 0 0
1241.21.61001 Boehringer Ingelheim Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
- Heidelberg
Recruitment postcode(s) [2] 0 0
- 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
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Washington
Country [8] 0 0
Austria
State/province [8] 0 0
Linz
Country [9] 0 0
Austria
State/province [9] 0 0
Wien
Country [10] 0 0
France
State/province [10] 0 0
Clichy
Country [11] 0 0
France
State/province [11] 0 0
Grenoble cédex 9
Country [12] 0 0
France
State/province [12] 0 0
Lyon
Country [13] 0 0
France
State/province [13] 0 0
Marseille
Country [14] 0 0
France
State/province [14] 0 0
Montpellier
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
France
State/province [16] 0 0
Vandoeuvre Cedex
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Germany
State/province [18] 0 0
Düsseldorf
Country [19] 0 0
Germany
State/province [19] 0 0
Esslingen
Country [20] 0 0
Germany
State/province [20] 0 0
Frankfurt am Main
Country [21] 0 0
Germany
State/province [21] 0 0
Hamburg
Country [22] 0 0
Germany
State/province [22] 0 0
Hannover
Country [23] 0 0
Germany
State/province [23] 0 0
Leipzig
Country [24] 0 0
Germany
State/province [24] 0 0
Mainz
Country [25] 0 0
New Zealand
State/province [25] 0 0
Auckland NZ
Country [26] 0 0
Portugal
State/province [26] 0 0
Aveiro
Country [27] 0 0
Portugal
State/province [27] 0 0
Coimbra
Country [28] 0 0
Portugal
State/province [28] 0 0
Lisboa
Country [29] 0 0
Portugal
State/province [29] 0 0
Porto
Country [30] 0 0
Romania
State/province [30] 0 0
Bucharest
Country [31] 0 0
Spain
State/province [31] 0 0
Barcelona
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid
Country [33] 0 0
Spain
State/province [33] 0 0
Majadahonda-Madrid
Country [34] 0 0
Spain
State/province [34] 0 0
Valencia
Country [35] 0 0
Switzerland
State/province [35] 0 0
Basel
Country [36] 0 0
Switzerland
State/province [36] 0 0
Bern
Country [37] 0 0
Switzerland
State/province [37] 0 0
St. Gallen
Country [38] 0 0
Switzerland
State/province [38] 0 0
Zürich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The substances BI 201335 and BI 207127 are being developed for the treatment of chronic
hepatitis C virus infection. BI 201335 and BI 207127 work by preventing the virus from
replicating.

The currently available medications pegylated interferon alfa and ribavirin for hepatitis C
ca have considerable adverse events in patients and in many cases are not sufficiently
effective. This is particularly the case in treatment of patients infected with genotype 1 of
HCV.

A combination therapy of these new substances without pegylated interferon alfa may be
associated with fewer adverse events that currently available (pegylated
interferon-alfa-based) medication and may also provide a treatment option to the large number
of patients with contraindications or intolerance to pegylated interferon alfa.

This clinical trial (1241.21) currently consists of 3 distinct studies: Part 1, Part 2 and
Part 3.

Part 1 (SOUND-C1) is a 2 armed study as described in experimental arms 1 and 2 below (actual
enrollment: 56 patients; randomized and treated: 32) Part 2 (SOUND-C2) is a 5 armed study as
described in experimental arms 3 to 7 below (actual enrollment: 465; randomized and treated:
362) Part 3 (SOUND-C3) includes 3 arms as described in experimental arms 8 to 10 below (83
patients randomized and treated)
Trial website
https://clinicaltrials.gov/ct2/show/NCT01132313
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
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