Chronic infection with HCV - genotype 1 MedDRA version: 17.0 Level: PT Classification code 10008912 Term: Chronic hepatitis C System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: BI 207127 NA / 200mg
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: BI 207127 NA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
P
Sponsors
Boehringer Ingelheim Pharma GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Chronic hepatitis C infection diagnosed by by positive anti-HCV antibodies and detected HCV RNA at screening in addition to at least one of the following: a. positive anti-HCV antibodies or detected HCV RNA at least 6 months prior to screening, OR b. liver biopsy indicating chronic HCV infection, OR c. history of elevated alanine aminotransferase (ALT) levels at least 6 months prior to screening. 2. HCV infection of sub-GT1b confirmed by genotypic testing at screening 3. Treatment naïve defined as: a. no prior treatment with any interferon, pegylated interferon, and /or ribavirin AND b. no prior treatment with at least one dose of any other licensed or investigational antiviral agent of for acute or chronic hepatitis C infection 4. Plasma HCV RNA = 1,000 IU/mL at screening 5. Liver biopsy within three years or fibroscan within 6 months prior to randomisation. Note: patients with a liver biopsy performed 3 or more years or fibroscan performed 6 months or more prior to randomisation demonstrating cirrhosis do not need to repeat a liver biopsy or fibroscan. Patients with a liver biopsy performed 3 or more years (or fibroscan performed 6 months or more) prior to randomisation, negative for the presence of cirrhosis need to repeat the liver biopsy or fibroscan, with the result available before randomisation visit. 6. Age 18 – 75 years (inclusive) 7. Female patients with a negative urine pregnancy test (dipstick) on Day 1 (Visit 2) prior to randomization a. with documented hysterectomy, OR b. who have had both ovaries removed, OR c. with documented tubal ligation, OR d. who are post-menopausal with last menstrual period at least 12 months prior to screening, OR e. of childbearing potential with a negative pregnancy test at screening, that agree to use two non-hormonal methods of birth control from the date of screening until 7 months after the last dose of ribavirin. They must not breast-feed at any time from the date of screening until 7 months after the last dose of ribavirin. Accepted methods of contraception for females in this trial are diaphragm with spermicide substances, intrauterine devices, cervical caps and condoms. Note: Systemic hormonal contraceptives may not be as effective in women taking BI 207127/FDV combination therapy and are not accepted methods of contraception in the study. OR Male patients a.who are documented to be sterile, OR b. who consistently and correctly use a condom while their female partners (if of child-bearing potential) agree to use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of ribavirin, AND c. without pregnant female partners. It is in the responsibility of the male patient to ensure that his partner (or partners) is not pregnant prior to enrolment into the study or becomes pregnant during the treatment and follow-up phase. Female partners of childbearing potential must perform monthly pregnancy tests from the date of screening until 7 months after the last dose of ribavirin (tests will be provided by the sponsor). 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 415 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: 1. HCV infection of mixed genotype (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening 2. HCV subtype 1a, mixed 1a/1b and GT1 undefined 3. Evidence of liver disease mainly due to causes other than chronic HCV infection such as autoimmune hepatitis, primary biliary cirrhosis, hemochromatosis or Wilson’s disease. Note: patients with steatosis as part of the histologic findings on liver biopsy are not excluded. 4. HIV-1 or HIV-2 infection 5. Hepatitis B virus (HBV) infection based on presence of HBs-Ag 6. Evidence of decompensated liver disease, or history of decompensated liver disease, defined as history of ascites, hepatic encephalopathy, bleeding esophageal varices or any other evidence of previous decompensation 7. International Normalized Ratio (INR) of =1.7 8. Serum albumin 2.0 times the upper limit of normal (ULN), unless history of Gilbert’s disease 10. 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) 11. Patients with ongoing or historical photosensitivity or recurrent rash 12. History of alcohol or drug abuse (except cannabis) within the past 12 months 13. Body mass index 35 kg/m2 14. Usage of any investigational drugs within 28 days prior to randomisation, or the planned usage of an investigational drug during the course of the current study 15. Known hypersensitivity to any ingredient of the study drugs 16. A condition that is insufficiently diagnosed, treated or clinically unstable which in the opinion of investigator may put the patient at risk because of participation in this study, influence the results of this study, or limit the patient’s ability to participate in this study 17. 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 18. A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease (e.g. congestive heart failure, myocardial infarction, unstable angina and arrhythmic disorders) current or within the previous 12 months before randomisation 19. Received concomitant hematopoietic growth factor, or immunomodulatory treatment within 28 days prior to randomisation 20. Received silymarin (milk thistle), glycyrrhizin, Sho-saiko-to (SST) or any medication listed in a restricted medication list provided in ISF within 28 days prior to randomisation, with the exception of parenteral analgesics used during liver biopsy procedure. The following exclusion criteria are potential contraindications for the use of PegIFN +/- RBV (for rationale please cf. Section 3.2) 21. Pre-existing psychiatric conditions including but not limited to severe depression or hospitalization for depression, suicidal ideation and attempted suicide, schizophrenia, bipolar illness, severe anxiety or personality disorder, a period of disability or impairment due to a psychiatric disease current or within the previous 3 years before randomisation 22. Abnormal thyroid function that cannot be controlled effectively by medication 23. Active autoimmune-mediated disease known to be exacerbated by peginterferon therapy (e.g., Crohn’s disease, ulcerative colitis, idiopathic thrombocytopenic purpura, syst
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Aim of the trial is to confirm efficacy and safety of treatment with 600 mg of BID BI 207127 in combination with 120 mg QD Faldaprevir (previously called BI 201335) and RBV for 16 and 24 weeks in target chronically infected HCV GT1b treatment naïve patients, including patients with compensated cirrhosis. The primary objective is to determine if a minimum historical target SVR12 rate of 71% can be achieved by the combination treatments of BI 207127, Faldaprevir and RBV, including adjustment for patients with compensated cirrhosis.;Secondary Objective: The secondary objective is to determine if there is a clinically meaningful difference between 16- and 24-week treatment durations. ;Primary end point(s): Sustained Virologic Response at Week 12 after end of active* treatment (SVR12): Plasma HCV RNA level <25 IU/mL at 12 weeks after end of active* treatment. *As patients included in Group 1 and respectively Groups 2 and 3 have different durations of active treatment, SVR 4, 12 and 24 will be assessed at different timepoints, taken into consideration the time after end of active treatment;Timepoint(s) of evaluation of this end point: 12 weeks after end of active treatment, meaning Week 28 for Group 1 (16 weeks of active therapy), and Week 36 for Groups 2 and 3 (24 weeks of active therapy), respectively | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - SVR4: Plasma HCV RNA level <25 IU/mL at 4 weeks after end of active* treatment. - SVR24: Plasma HCV RNA level <25 IU/mL at 24 weeks after end of active* treatment. *As patients included in Group 1 and respectively Groups 2 and 3 have different durations of active treatment, SVR 4, 12 and 24 will be assessed at different timepoints, taken into consideration the time after end of active treatment;Timepoint(s) of evaluation of this end point: SVR 4: 4 weeks after end of active treatment, meaning Week 20 for Group 1 (16 weeks of active therapy), and Week 28 for Groups 2 and 3 (24 weeks of active therapy),respectively. SVR 24: 24 weeks after end of active treatment, meaning Week 40 for Group 1 (16 weeks of active therapy), and Week 48 for Groups 2 and 3 (24 weeks of active therapy), respectively | — |
Countries
Austria, Canada, France, Germany, Hungary, Ireland, Italy, Netherlands, Portugal, Romania, Spain, United Kingdom, United States
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed