chronic hepatitis C infection of genotype 1 MedDRA version: 17.1 Level: LLT Classification code 10019751 Term: Hepatitis C virus System Organ Class: 100000004848
Conditions
Interventions
Product Name: BI 201335 NA / 120mg
Pharmaceutical Form: Capsule, soft
Current Sponsor code: BI 201335 NA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-
Produ
Sponsors
Unilfarma, Lda.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Chronic hepatitis C infection, diagnosed by positive HCV serology test (HCV Ab positive) or detectable HCV RNA at least 6 months prior to screening, or by a liver biopsy typical of chronic hepatitis C in combination with positive HCV serology 2)HCV infection of genotype 1 (1a or 1b) confirmed by genotypic testing at screening. Note: if central lab is unable to differentiate the subtype, a recent subtyping from local lab within 6 months prior to screening will be accepted for stratification. 3)Treatment naive, defined as no prior treatment with any interferon, pegylated interferon, and /or ribavirin and no prior treatment with at least one dose of any direct antiviral agent for acute or chronic hepatitis C infection 4)Plasma HCV RNA = 100,000 IU/mL at screening 5)Liver biopsy within two years or fibroscan within six months prior to screening. Note: In Part 1, cirrhosis has to be excluded, whereas in Part 2, Part 3 patients with Child-Pugh A cirrhosis are eligible. Fibrosis stage (according to biopsy or fibroscan) has to be documented. 6)Age 18 – 75 years 7)Female patients who are infertile or who are of childbearing potential with a negative pregnancy test at screening and on Day 1 (Visit 2), that either agree to abstain from intercourse, or agree to use two non-hormonal methods of birth control from the date of screening until 7 months after the last dose of ribavirin. Accepted methods of contraception in the study include diaphragm with a spermicidal substance, cervical caps, intrauterine devices and condoms. Note: Systemic hormonal contraceptives may not be as effective in women taking BI 207127/BI 201335 combination therapy and are not accepted methods of contraception in this study. Patients must not breast-feed at any time from the date of screening until 7 months after the last dose of ribavirin, OR Male patients who are sterile, or who agree to abstain from intercourse or who use a condom while their female partners use one medically accepted method of birth control 8)Signed informed consent form prior to trial participation Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 350 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 51
Exclusion criteria
Exclusion criteria: 1) Hepatitis C infection of mixed genotype (1/2, 1/3, and 1/4) or mixed subgenotype 1a/b diagnosed by genotypic testing at screeningdiagnosed by genotypic testing at screening 2) Evidence of liver disease due to causes other than chronic HCV infection 3) Positive ELISA for HIV-1 or HIV-2 4) Hepatitis B virus (HBV) infection based on presence of HBs-Ag 5) Decompensated liver disease, or history of decompensated liver disease 6) Active or suspected malignancy or history of malignancy within the last 5 years (with the exception of appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix) 7) Patients with ongoing or historical photosensitivity or recurrent rash 8) History of alcohol or drug abuse (except cannabis) within the past 12 months 9) Body mass index 35 kg/m2 10) Usage of any investigational drugs within 30 days prior to randomisation, or 5 half-lives, whichever is longer; or the planned usage of an investigational drug during the course of the current study 11) Known hypersensitivity to any ingredient of the study drugs 12) A condition that is defined as one which in the opinion of the investigator may either interfere with the patient’s capability for participation in the trial or may influence the results of the trial or the patient’s ability to participate in the trial. 13) Alpha fetoprotein value >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 14) Total bilirubin > 1.5 x ULN with ratio of direct/indirect > 1 15) AST or ALT > 5 x ULN 16) Prothrombin time INR (International Normalised Ratio) prolonged to >1.5 x ULN 17) Requirement for chronic systemic corticosteroids (nasal or pulmonary steroids will be allowed) 18) Received concomitant systemic antiviral, hematopoietic growth factor, or immunomodulatory treatment with 30 days prior to randomisation or 5 half-lives, whichever is longer; patients being treated with oral antivirals such as acyclovir, famcyclovir, valcyclovir for mild, localised recurrent herpes simplex infection, or with oseltamivir and zanamivir for Influenza A may be enrolled. 19) Received silymarin (milk thistle) or glycyrrhizin or Sho-saiko-to (SST) within 30 days prior to randomisation 20) Use of any of the medications listed in Appendix 10.2 within 30 days prior to randomisation 21) Hemoglobin 1xULN or creatinine clearance =50 ml/min 27) HbA1c > 7.5% 28) TSH and T4 outside normal limits (accepted if thyroid function adequately controlled) 29) Chronic obstructive pulmonary disease 30) Screening ECG with any abnormalities suggestive of prior or active cardiovascular disease 31) Chronic cardiac disease (e.g., coronary artery disease, congestive heart failure, uncontrolled hypertension, significant arrhythmia) 32) Autoimmune disease, including autoimmune hepatitis 33) Hemoglobinopathy (e.g., thalassemia major or sickle cell anemia) 34) Glucose-6-phosphate dehydrogenase deficiency 35) History of moderate, severe or uncontrolled psychiatric disease, especially depression, including a history of hospitalization or prior suicidal attempt 36) Abnormal find
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: Safety, antiviral effect and evaluation of any pharmacokinetic (PK) interactions of BI 207127 in combination with BI 201335 and ribavirin for 4 weeks in treatment-naïve patients with chronic HCV genotype 1 infection. Part 2: Safety and antiviral effect of BI 207127 in combination with BI 201335, with or without ribavirin for 16, 28 or 40 weeks in patients with chronic HCV genotype 1 infection. Part 3: Safety, antiviral effect and pharmacokinetics of additional dosing regimens of BI 201335 and BI 207127 combination therapy with ribavirin; and without BI 207127 induction dose (1200mg of BI 207127 as first intake at Day 1) in treatment-naïve GT1 chronic HCV patients. ;Secondary Objective: N.a.;Primary end point(s): Part 1: Plasma HCV RNA level <25 IU/mL (detectable or undetectable)* at Week 4 Part 2: Sustained Virological Response Week 12 (SVR12): Plasma HCV RNA not detectable * at 12 weeks after completion of all therapy. Part 3: Sustained Virological Response at 4 Weeks after completion of all therapy (SVR-4): Plasma HCV RNA level undetectable 12 weeks after completion of all therapy *Plasma HCV RNA level will be measured using the quantitative Roche COBAS® Taqman HCV/HPS assay. HCV RNA levels <25 IU/mL will be analysed and reported as being undetectable or detectable.;Timepoint(s) of evaluation of this end point: Part 1: Week 4 Part 2: Week 40, 52, or 64 (depending on treatment group assignment) Part 3: Week 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 and 2: •Time to virological response: Timepoint of the first measurement of undetectable plasma HCV RNA level •Plasma HCV RNA level not detectable at Week 4 •Sustained Virological Response at 12 Weeks after completion of all therapy (SVR-12): Plasma HCV RNA level not detectable at 12 weeks after completion of all therapy Part 3: • Plasma HCV RNA level <25 IU/mL at Week 4 and 12 • Sustained Virological Response at 12 Weeks after completion of all therapy (SVR-12): Plasma HCV RNA level undetectable 12 weeks after completion of all therapy;Timepoint(s) of evaluation of this end point: Part 1 and 2: -For time to virological response: any timepoint -Plasma HCV RNA level not detectable at Week 4: Week 4 -SVR-12: Week 28, 40, 52 (depending on treatment group assignment) Part 3: - Plasma HCV RNA level <25 IU/mL at Week 4 and 12: Week 4 and week 12 - SVR-12: Week 28 and Week 36. | — |
Countries
Australia, Austria, France, Germany, New Zealand, Portugal, Romania, Spain, Switzerland
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim International GmbH
Outcome results
None listed