Overview

This trial is active, not recruiting.

Condition hepatitis c, chronic
Treatments bi 207127, bi 201335, ribavirin, bi 207217
Phase phase 2
Sponsor Boehringer Ingelheim
Start date May 2010
End date October 2014
Trial size 490 participants
Trial identifier NCT01132313, 1241.21, 2009-018197-66

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)

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
4 weeks of high dose TID BI 207127 and QD BI 201335 in combination with RBV, Part 1
ribavirin
48 weeks, according to label
bi 201335
24 weeks, QD
bi 207127
4 weeks, high dose, TID
(Experimental)
4 weeks of low dose three times per day (TID) BI 207127 and once daily (QD) BI 201335 in combination with RBV, Part 1
bi 207127
4 weeks, low dose TID
bi 201335
24 weeks, QD
ribavirin
48 weeks, according to label
(Experimental)
16 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2
bi 207127
16 weeks, high dose, TID
bi 201335
16 weeks, QD
ribavirin
16 weeks, according to label
(Experimental)
28 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2
bi 207127
28 weeks, high dose, TID
ribavirin
28 weeks, according to label
bi 201335
28 weeks, QD
(Experimental)
40 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2
bi 201335
40 weeks, QD
bi 207127
40 weeks, high dose, TID
ribavirin
40 weeks, according to label
(Experimental)
28 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 2
ribavirin
28 weeks, according to label
bi 201335
28 weeks, QD
bi 207217
28 weeks, high dose BID
(Experimental)
28 weeks of TID BI 207127 and QD BI 201335 without RBV, Part 2
bi 207127
28 weeks, high dose, TID
bi 201335
28 weeks, QD
(Experimental)
16 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 3
bi 207127
16 weeks, high dose, BID
ribavirin
16 weeks, according to label
bi 201335
16 weeks, QD
(Experimental)
24 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 3
bi 207127
24 weeks, very high dose, BID
bi 201335
24 weeks, QD
ribavirin
24 weeks, according to label
(Experimental)
24 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 3
bi 201335
24 weeks, QD
bi 207127
24 weeks, high dose, TID
ribavirin
24 weeks, according to label
(Experimental)
16 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 4
ribavirin
16 weeks, according to label
bi 207127
16 weeks, standard dose, BID
bi 201335
16 weeks, QD
(Experimental)
24 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 4
ribavirin
24 weeks, according to label
bi 201335
24 weeks, QD
bi 207127
24 weeks, standard dose, BID

Primary Outcomes

Measure
Part 1 of the trial: Rapid virological response (RVR), defined as HCV RNA <25IU/mL at Week 4 of treatment
time frame: 4 weeks
Part 2 of the trial: Sustained virological response (SVR), defined as HCV RNA <25 IU/mL and undetectable at 12 weeks after end of treatment
time frame: up to 52 weeks
Part 3 and 4: Sustained virological response (SVR) defined as HCV RNA <25IU/mL and undetectable at 12 weeks after end of treatment
time frame: up to 36 weeks

Secondary Outcomes

Measure
Part 1 and 2: Time to virological response, defined as the timepoint of the first measurement of plasma HCV RNA level <25 IU/mL
time frame: up to 40 weeks
Part 1 and2: Plasma HCV RNA level not detectable at Week 4
time frame: 4 weeks
Part 2: Sustained virological response at 24 weeks after end of treatment
time frame: up to 64 weeks
Part 3 and 4: Plasma HCV RNA level <25 IU/mL at week 4 and 12 of treatment
time frame: week 4 and 12
Part 3 and 4: Sustained virological response (SVR) at 4 weeks after end of treatment
time frame: up to 28 weeks

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

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

Additional Information

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)
Trial information was received from ClinicalTrials.gov and was last updated in October 2014.
Information provided to ClinicalTrials.gov by Boehringer Ingelheim.