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 - Full Text View

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:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

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: Yes ]
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: Yes ]
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: 12 weeks ] [ 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:	517
Study Start Date:	May 2010
Estimated Study Completion Date:	October 2015
Estimated Primary Completion Date:	October 2015 (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: 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
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

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

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

Contacts

Contact: Boehringer Ingelheim Call Center

1-800-243-0127

clintriage.rdg@boehringer-ingelheim.com

Show 51 Study Locations

Sponsors and Collaborators

Boehringer Ingelheim Pharmaceuticals

Investigators

Study Chair:

Boehringer Ingelheim

Boehringer Ingelheim Pharmaceuticals

More Information

No publications provided

Responsible Party:	Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01132313 History of Changes
Other Study ID Numbers:	1241.21, 2009-018197-66
Study First Received:	May 3, 2010
Last Updated:	May 15, 2013
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 May 19, 2013