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: July 23, 2014
Last verified: July 2014

May 3, 2010
July 23, 2014
May 2010
October 2014   (final data collection date for primary outcome 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 ] [ 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 ]
  • 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: Yes ]
  • Part 2 of the trial: Sustained virological response (SVR), defined as HCV RNA <25 IU/mL at 6 months after end of treatment [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01132313 on ClinicalTrials.gov Archive Site
  • 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 ]
Time to virological response, defined as the timepoint of the first measurement of plasma HCV RNA level <25 IU/mL [ Time Frame: up to 48 weeks ]
Not Provided
Not Provided
 
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
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)

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)

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Hepatitis C, Chronic
  • Drug: BI 207127
    28 weeks, high dose, TID
  • Drug: BI 201335
    40 weeks, QD
  • Drug: BI 207127
    4 weeks, low dose TID
  • Drug: BI 201335
    24 weeks, QD
  • Drug: Ribavirin
    16 weeks, according to label
  • Drug: Ribavirin
    28 weeks, according to label
  • Drug: BI 207127
    40 weeks, high dose, TID
  • Drug: BI 207127
    24 weeks, very high dose, BID
  • Drug: BI 207127
    16 weeks, standard dose, BID
  • Drug: Ribavirin
    48 weeks, according to label
  • Drug: Ribavirin
    40 weeks, according to label
  • Drug: BI 207127
    16 weeks, high dose, TID
  • Drug: BI 201335
    28 weeks, QD
  • Drug: BI 201335
    16 weeks, QD
  • Drug: Ribavirin
    24 weeks, according to label
  • Drug: BI 207127
    24 weeks, standard dose, BID
  • Drug: BI 207127
    16 weeks, high dose, BID
  • Drug: BI 207217
    28 weeks, high dose BID
  • Drug: BI 207127
    24 weeks, high dose, TID
  • Drug: BI 207127
    4 weeks, high dose, TID
  • Experimental: 2
    4 weeks of high dose TID BI 207127 and QD BI 201335 in combination with RBV, Part 1
    Interventions:
    • Drug: Ribavirin
    • Drug: BI 201335
    • Drug: BI 207127
  • 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
    Interventions:
    • Drug: BI 207127
    • Drug: BI 201335
    • Drug: Ribavirin
  • Experimental: 3
    16 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2
    Interventions:
    • Drug: BI 207127
    • Drug: BI 201335
    • Drug: Ribavirin
  • Experimental: 4
    28 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2
    Interventions:
    • Drug: BI 207127
    • Drug: Ribavirin
    • Drug: BI 201335
  • Experimental: 5
    40 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2
    Interventions:
    • Drug: BI 201335
    • Drug: BI 207127
    • Drug: Ribavirin
  • Experimental: 6
    28 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 2
    Interventions:
    • Drug: Ribavirin
    • Drug: BI 201335
    • Drug: BI 207217
  • Experimental: 7
    28 weeks of TID BI 207127 and QD BI 201335 without RBV, Part 2
    Interventions:
    • Drug: BI 207127
    • Drug: BI 201335
  • Experimental: 8
    16 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 3
    Interventions:
    • Drug: BI 207127
    • Drug: Ribavirin
    • Drug: BI 201335
  • Experimental: 9
    24 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 3
    Interventions:
    • Drug: BI 207127
    • Drug: BI 201335
    • Drug: Ribavirin
  • Experimental: 10
    24 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 3
    Interventions:
    • Drug: BI 201335
    • Drug: BI 207127
    • Drug: Ribavirin
  • Experimental: 11
    16 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 4
    Interventions:
    • Drug: Ribavirin
    • Drug: BI 207127
    • Drug: BI 201335
  • Experimental: 12
    24 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 4
    Interventions:
    • Drug: Ribavirin
    • Drug: BI 201335
    • Drug: BI 207127

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
490
October 2014
October 2014   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Austria,   France,   Germany,   New Zealand,   Portugal,   Romania,   Spain,   Switzerland
 
NCT01132313
1241.21, 2009-018197-66
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP