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Trial details imported from ClinicalTrials.gov

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

2009-018197-66

Secondary ID [2]

1241.21

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Hepatitis C, Chronic

Condition category

Condition code

Infection

Other infectious diseases

Oral and Gastrointestinal

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]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Part 1: Rapid Virological Response (RVR)

Timepoint [1]

4 weeks

Primary outcome [2]

Part 2: Sustained Virological Response (SVR)

Timepoint [2]

From drug administration until 12 weeks after end of treatment, up to 52 weeks

Primary outcome [3]

Part 3 and 4: Sustained Virological Response (SVR)

Timepoint [3]

From drug administration until 12 weeks after end of treatment, up to 36 weeks

Secondary outcome [1]

Part 1: Time to Virological Response

Timepoint [1]

From drug administration until end of drug administration, up to 4 weeks

Secondary outcome [2]

Part 2: Time to Virological Response

Timepoint [2]

From drug administration until end of drug administration, up to 40 weeks

Secondary outcome [3]

Part 1 and 2: Plasma HCV RNA Level Not Detectable at Week 4

Timepoint [3]

4 weeks

Secondary outcome [4]

Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment

Timepoint [4]

4 weeks and 24 weeks after the end of treatment, up to 64 weeks

Secondary outcome [5]

Part 3 and 4: Plasma HCV RNA Level <25 IU/mL at Week 4 and 12 of Treatment

Timepoint [5]

Week 4 and 12

Secondary outcome [6]

Part 3 and 4: Sustained Virological Response (SVR) at 4 Weeks After End of Treatment

Timepoint [6]

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?

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]

1241.21.61002 Boehringer Ingelheim Investigational Site - Heidelberg

Recruitment hospital [2]

1241.21.61001 Boehringer Ingelheim Investigational Site - Melbourne

Recruitment postcode(s) [1]

- Heidelberg

Recruitment postcode(s) [2]

- Melbourne

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

California

Country [2]

United States of America

State/province [2]

Florida

Country [3]

United States of America

State/province [3]

Indiana

Country [4]

United States of America

State/province [4]

Massachusetts

Country [5]

United States of America

State/province [5]

North Carolina

Country [6]

United States of America

State/province [6]

Texas

Country [7]

United States of America

State/province [7]

Washington

Country [8]

Austria

State/province [8]

Linz

Country [9]

Austria

State/province [9]

Wien

Country [10]

France

State/province [10]

Clichy

Country [11]

France

State/province [11]

Grenoble cédex 9

Country [12]

France

State/province [12]

Lyon

Country [13]

France

State/province [13]

Marseille

Country [14]

France

State/province [14]

Montpellier

Country [15]

France

State/province [15]

Paris

Country [16]

France

State/province [16]

Vandoeuvre Cedex

Country [17]

Germany

State/province [17]

Berlin

Country [18]

Germany

State/province [18]

Düsseldorf

Country [19]

Germany

State/province [19]

Esslingen

Country [20]

Germany

State/province [20]

Frankfurt am Main

Country [21]

Germany

State/province [21]

Hamburg

Country [22]

Germany

State/province [22]

Hannover

Country [23]

Germany

State/province [23]

Leipzig

Country [24]

Germany

State/province [24]

Mainz

Country [25]

New Zealand

State/province [25]

Auckland NZ

Country [26]

Portugal

State/province [26]

Aveiro

Country [27]

Portugal

State/province [27]

Coimbra

Country [28]

Portugal

State/province [28]

Lisboa

Country [29]

Portugal

State/province [29]

Porto

Country [30]

Romania

State/province [30]

Bucharest

Country [31]

Spain

State/province [31]

Barcelona

Country [32]

Spain

State/province [32]

Madrid

Country [33]

Spain

State/province [33]

Majadahonda-Madrid

Country [34]

Spain

State/province [34]

Valencia

Country [35]

Switzerland

State/province [35]

Basel

Country [36]

Switzerland

State/province [36]

Bern

Country [37]

Switzerland

State/province [37]

St. Gallen

Country [38]

Switzerland

State/province [38]

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/study/NCT01132313

Trial related presentations / publications

Zeuzem S, Mantry P, Soriano V, Buynak RJ, Dufour JF, Pockros PJ, Wright D, Angus P, Buti M, Stern JO, Kadus W, Vinisko R, Bocher W, Mensa FJ. Short article: Faldaprevir, deleobuvir and ribavirin in IL28B non-CC patients with HCV genotype-1a infection included in the SOUND-C3 phase 2b study. Eur J Gastroenterol Hepatol. 2016 Aug;28(8):923-6. doi: 10.1097/MEG.0000000000000649.
Asselah T, Zeuzem S, Soriano V, Bronowicki JP, Lohse AW, Mullhaupt B, Schuchmann M, Bourliere M, Buti M, Roberts SK, Gane EJ, Stern JO, Voss F, Baum P, Gallivan JP, Bocher WO, Mensa FJ. ITPA Genotypes Predict Anemia but Do Not Affect Virological Response with Interferon-Free Faldaprevir, Deleobuvir, and Ribavirin for HCV Infection. PLoS One. 2015 Dec 9;10(12):e0144004. doi: 10.1371/journal.pone.0144004. eCollection 2015.
Zeuzem S, Soriano V, Asselah T, Gane EJ, Bronowicki JP, Angus P, Lohse AW, Stickel F, Mullhaupt B, Roberts S, Schuchmann M, Manns M, Bourliere M, Buti M, Stern JO, Gallivan JP, Voss F, Sabo JP, Bocher W, Mensa FJ; SOUND-C2 Study Group. Efficacy and safety of faldaprevir, deleobuvir, and ribavirin in treatment-naive patients with chronic hepatitis C virus infection and advanced liver fibrosis or cirrhosis. Antimicrob Agents Chemother. 2015 Feb;59(2):1282-91. doi: 10.1128/AAC.04383-14. Epub 2014 Dec 15.
Zeuzem S, Soriano V, Asselah T, Bronowicki JP, Lohse AW, Mullhaupt B, Schuchmann M, Bourliere M, Buti M, Roberts SK, Gane EJ, Stern JO, Vinisko R, Kukolj G, Gallivan JP, Bocher WO, Mensa FJ. Faldaprevir and deleobuvir for HCV genotype 1 infection. N Engl J Med. 2013 Aug 15;369(7):630-9. doi: 10.1056/NEJMoa1213557.
Zeuzem S, Asselah T, Angus P, Zarski JP, Larrey D, Mullhaupt B, Gane E, Schuchmann M, Lohse AW, Pol S, Bronowicki JP, Roberts S, Arasteh K, Zoulim F, Heim M, Stern JO, Nehmiz G, Kukolj G, Bocher WO, Mensa FJ. Faldaprevir (BI 201335), deleobuvir (BI 207127) and ribavirin oral therapy for treatment-naive HCV genotype 1: SOUND-C1 final results. Antivir Ther. 2013;18(8):1015-9. doi: 10.3851/IMP2567. Epub 2013 Apr 4.

Public notes

Contacts

Principal investigator

Name

Boehringer Ingelheim

Address

Boehringer Ingelheim

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01132313

Trial Review

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