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

Hepatitis C, Chronic Clinical Trial

Official 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01132313
• Other study ID #: 1241.21
• Secondary ID: 2009-018197-66
• Status: Completed
• Phase: Phase 2
• First received: May 3, 2010
• Last updated: December 22, 2015
• Start date: May 2010
• Est. completion date: October 2014

Study information

• Verified date: December 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Dept of Health and Ageing Therapeutic Goods AdminAustria: Medicines and Medical Devices AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesNew Zealand: MedsafePortugal: National Pharmacy and Medicines InstituteRomania: National Medicines AgencySpain: Spanish Agency of MedicinesSwitzerland: SwissmedicUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 488
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis C, Chronic

Intervention

Drug:
• BI 207127
28 weeks, high dose, TID
• BI 201335
40 weeks, QD
• BI 207127
4 weeks, low dose TID
• BI 201335
24 weeks, QD
• Ribavirin
16 weeks, according to label
• Ribavirin
28 weeks, according to label
• Ribavirin
28 weeks, according to label
• BI 207127
40 weeks, high dose, TID
• BI 207127
24 weeks, very high dose, BID
• BI 207127
16 weeks, standard dose, BID
• BI 201335
24 weeks, QD
• Ribavirin
48 weeks, according to label
• Ribavirin
40 weeks, according to label
• BI 207127
16 weeks, high dose, TID
• BI 207127
28 weeks, high dose, TID
• BI 201335
28 weeks, QD
• BI 201335
16 weeks, QD
• Ribavirin
24 weeks, according to label
• BI 201335
24 weeks, QD
• BI 201335
28 weeks, QD
• BI 207127
24 weeks, standard dose, BID
• BI 201335
24 weeks, QD
• BI 201335
16 weeks, QD
• BI 207127
16 weeks, high dose, BID
• BI 201335
24 weeks, QD
• Ribavirin
16 weeks, according to label
• Ribavirin
16 weeks, according to label
• BI 207217
28 weeks, high dose BID
• BI 201335
16 weeks, QD
• BI 207127
24 weeks, high dose, TID
• Ribavirin
48 weeks, according to label
• BI 207127
4 weeks, high dose, TID
• BI 201335
28 weeks, QD
• Ribavirin
24 weeks, according to label
• Ribavirin
24 weeks, according to label

Locations

Country	Name	City	State
Australia	1241.21.61002 Boehringer Ingelheim Investigational Site	Heidelberg	Victoria
Australia	1241.21.61001 Boehringer Ingelheim Investigational Site	Melbourne	Victoria
Austria	1241.21.43003 Boehringer Ingelheim Investigational Site	Linz
Austria	1241.21.43001 Boehringer Ingelheim Investigational Site	Wien
Austria	1241.21.43002 Boehringer Ingelheim Investigational Site	Wien
France	1241.21.33005 Boehringer Ingelheim Investigational Site	Clichy
France	1241.21.33007 Boehringer Ingelheim Investigational Site	Grenoble cédex 9
France	1241.21.33003 Boehringer Ingelheim Investigational Site	Lyon
France	1241.21.33001 Boehringer Ingelheim Investigational Site	Marseille
France	1241.21.33002 Boehringer Ingelheim Investigational Site	Montpellier
France	1241.21.33004 Boehringer Ingelheim Investigational Site	Paris
France	1241.21.33008 Boehringer Ingelheim Investigational Site	Paris
France	1241.21.33006 Boehringer Ingelheim Investigational Site	Vandoeuvre Cedex
Germany	1241.21.49002 Boehringer Ingelheim Investigational Site	Berlin
Germany	1241.21.49003 Boehringer Ingelheim Investigational Site	Berlin
Germany	1241.21.49007 Boehringer Ingelheim Investigational Site	Düsseldorf
Germany	1241.21.49005 Boehringer Ingelheim Investigational Site	Esslingen
Germany	1241.21.49001 Boehringer Ingelheim Investigational Site	Frankfurt am Main
Germany	1241.21.49006 Boehringer Ingelheim Investigational Site	Hamburg
Germany	1241.21.49009 Boehringer Ingelheim Investigational Site	Hannover
Germany	1241.21.49004 Boehringer Ingelheim Investigational Site	Leipzig
Germany	1241.21.49008 Boehringer Ingelheim Investigational Site	Mainz
New Zealand	1241.21.64001 Boehringer Ingelheim Investigational Site	Auckland NZ
Portugal	1241.21.35103 Boehringer Ingelheim Investigational Site	Aveiro
Portugal	1241.21.35104 Boehringer Ingelheim Investigational Site	Coimbra
Portugal	1241.21.35101 Boehringer Ingelheim Investigational Site	Lisboa
Portugal	1241.21.35105 Boehringer Ingelheim Investigational Site	Lisboa
Portugal	1241.21.35102 Boehringer Ingelheim Investigational Site	Porto
Romania	1241.21.40001 Boehringer Ingelheim Investigational Site	Bucharest
Romania	1241.21.40002 Boehringer Ingelheim Investigational Site	Bucharest
Romania	1241.21.40003 Boehringer Ingelheim Investigational Site	Bucharest
Spain	1241.21.34002 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1241.21.34005 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1241.21.34003 Boehringer Ingelheim Investigational Site	Madrid
Spain	1241.21.34004 Boehringer Ingelheim Investigational Site	Madrid
Spain	1241.21.34001 Boehringer Ingelheim Investigational Site	Majadahonda-Madrid
Spain	1241.21.34006 Boehringer Ingelheim Investigational Site	Valencia
Switzerland	1241.21.41003 Boehringer Ingelheim Investigational Site	Basel
Switzerland	1241.21.41006 Boehringer Ingelheim Investigational Site	Bern
Switzerland	1241.21.41001 Boehringer Ingelheim Investigational Site	St. Gallen
Switzerland	1241.21.41002 Boehringer Ingelheim Investigational Site	Zürich
United States	1241.21.0012 Boehringer Ingelheim Investigational Site	Arlington	Texas
United States	1241.21.0005 Boehringer Ingelheim Investigational Site	Austin	Texas
United States	1241.21.0007 Boehringer Ingelheim Investigational Site	Dallas	Texas
United States	1241.21.0019 Boehringer Ingelheim Investigational Site	Fayetteville	North Carolina
United States	1241.21.0010 Boehringer Ingelheim Investigational Site	Houston	Texas
United States	1241.21.0003 Boehringer Ingelheim Investigational Site	La Jolla	California
United States	1241.21.0011 Boehringer Ingelheim Investigational Site	Palm Harbor	Florida
United States	1241.21.0006 Boehringer Ingelheim Investigational Site	San Diego	California
United States	1241.21.0004 Boehringer Ingelheim Investigational Site	San Francisco	California
United States	1241.21.0017 Boehringer Ingelheim Investigational Site	Seattle	Washington
United States	1241.21.0008 Boehringer Ingelheim Investigational Site	Springfield	Massachusetts
United States	1241.21.0013 Boehringer Ingelheim Investigational Site	Valparaiso	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Australia,  Austria,  France,  Germany,  New Zealand,  Portugal,  Romania,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Rapid Virological Response (RVR)	Part 1: Rapid virological response (RVR), defined as Hepatitis C Virus Ribonucleic acid (HCV RNA) <25IU/mL at Week 4 of treatment	4 weeks	No
Primary	Part 2: Sustained Virological Response (SVR)	Part 2: Sustained virological response (SVR), defined as HCV RNA <25 IU/mL and undetectable at 12 weeks after end of treatment	From drug administration until 12 weeks after end of treatment, up to 52 weeks	No
Primary	Part 3 and 4: Sustained Virological Response (SVR)	Part 3 and 4: Sustained virological response (SVR) defined as HCV RNA <25IU/mL and undetectable at 12 weeks after end of treatment	From drug administration until 12 weeks after end of treatment, up to 36 weeks	No
Secondary	Part 1: Time to Virological Response	Part 1: Time to virological response, defined as the timepoint of the first measurement of plasma HCV RNA level <25 IU/mL. The percentage of participants who achieved virological response within each time period are displayed for this outcome measure.	From drug administration until end of drug administration, up to 4 weeks	No
Secondary	Part 2: Time to Virological Response	Part 2: Time to virological response, defined as the timepoint of the first measurement of plasma HCV RNA level <25 IU/mL. The percentage of participants who achieved virological response within each time period are displayed for this outcome measure.	From drug administration until end of drug administration, up to 40 weeks	No
Secondary	Part 1 and 2: Plasma HCV RNA Level Not Detectable at Week 4	Part 1 and 2: Plasma Hepatitis C Virus Ribonucleic acid (HCV RNA) level not detectable at Week 4	4 weeks	No
Secondary	Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment	Part 2: Sustained virological response at 4 and 24 weeks after end of treatment	4 weeks and 24 weeks after the end of treatment, up to 64 weeks	No
Secondary	Part 3 and 4: Plasma HCV RNA Level <25 IU/mL at Week 4 and 12 of Treatment	Part 3 and 4: Plasma Hepatitis C Virus Ribonucleic acid (HCV RNA) level <25 IU/mL at week 4 and 12 of treatment	Week 4 and 12	No
Secondary	Part 3 and 4: Sustained Virological Response (SVR) at 4 Weeks After End of Treatment	Part 3 and 4: Sustained virological response (SVR) at 4 weeks after end of treatment	up to 28 weeks	No

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