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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01132313
First received: May 3, 2010
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

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)


Condition Intervention Phase
Hepatitis C, Chronic
Drug: BI 207127
Drug: BI 201335
Drug: Ribavirin
Drug: BI 207217
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Part 1 of the trial: Rapid virological response (RVR), defined as HCV RNA <25IU/mL at Week 4 of treatment [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Part 1 and2: Plasma HCV RNA level not detectable at Week 4 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Part 2: Sustained virological response at 24 weeks after end of treatment [ Time Frame: up to 64 weeks ] [ Designated as safety issue: No ]
  • Part 3 and 4: Plasma HCV RNA level <25 IU/mL at week 4 and 12 of treatment [ Time Frame: week 4 and 12 ] [ Designated as safety issue: No ]
  • Part 3 and 4: Sustained virological response (SVR) at 4 weeks after end of treatment [ Time Frame: up to 28 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 490
Study Start Date: May 2010
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 2
4 weeks of high dose TID BI 207127 and QD BI 201335 in combination with RBV, Part 1
Drug: Ribavirin
48 weeks, according to label
Drug: BI 201335
24 weeks, QD
Drug: BI 207127
4 weeks, high dose, TID
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
Drug: BI 207127
4 weeks, low dose TID
Drug: BI 201335
24 weeks, QD
Drug: Ribavirin
48 weeks, according to label
Experimental: 3
16 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2
Drug: BI 207127
16 weeks, high dose, TID
Drug: BI 201335
16 weeks, QD
Drug: Ribavirin
16 weeks, according to label
Experimental: 4
28 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2
Drug: BI 207127
28 weeks, high dose, TID
Drug: Ribavirin
28 weeks, according to label
Drug: BI 201335
28 weeks, QD
Experimental: 5
40 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2
Drug: BI 201335
40 weeks, QD
Drug: BI 207127
40 weeks, high dose, TID
Drug: Ribavirin
40 weeks, according to label
Experimental: 6
28 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 2
Drug: Ribavirin
28 weeks, according to label
Drug: BI 201335
28 weeks, QD
Drug: BI 207217
28 weeks, high dose BID
Experimental: 7
28 weeks of TID BI 207127 and QD BI 201335 without RBV, Part 2
Drug: BI 207127
28 weeks, high dose, TID
Drug: BI 201335
28 weeks, QD
Experimental: 8
16 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 3
Drug: BI 207127
16 weeks, high dose, BID
Drug: Ribavirin
16 weeks, according to label
Drug: BI 201335
16 weeks, QD
Experimental: 9
24 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 3
Drug: BI 207127
24 weeks, very high dose, BID
Drug: BI 201335
24 weeks, QD
Drug: Ribavirin
24 weeks, according to label
Experimental: 10
24 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 3
Drug: BI 201335
24 weeks, QD
Drug: BI 207127
24 weeks, high dose, TID
Drug: Ribavirin
24 weeks, according to label
Experimental: 11
16 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 4
Drug: Ribavirin
16 weeks, according to label
Drug: BI 207127
16 weeks, standard dose, BID
Drug: BI 201335
16 weeks, QD
Experimental: 12
24 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 4
Drug: Ribavirin
24 weeks, according to label
Drug: BI 201335
24 weeks, QD
Drug: BI 207127
24 weeks, standard dose, BID

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01132313

  Show 53 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01132313     History of Changes
Other Study ID Numbers: 1241.21, 2009-018197-66
Study First Received: May 3, 2010
Last Updated: August 6, 2014
Health Authority: Australia: Dept of Health and Ageing Therapeutic Goods Admin
Austria: Medicines and Medical Devices Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
New Zealand: Medsafe
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Antiviral Agents
Ribavirin
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014