Safety, antiviral effect and pharmacokinetics of BI 207127 in combination with BI 201335 and with or without ribavirin for 4, 16, 28 or 40 weeks in patients with chronic HCV genotype 1 infection (randomized, Phase Ib/II)

INTERVENTION: 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‐ Product Name: BI 207127 NA / 200mg Pharmaceutical Form: Tablet Current Sponsor code: BI 207127 NA Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Trade Name: Copegus 200mg (Ribavirin) Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: RIBAVIRIN CAS Number: 36791‐04‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Trade Name: Pegasys (pegylated interferon‐a 2a) Pharmaceutical Form: Solution for injection INN or Proposed INN: PEGINTERFERON ALFA 2A CAS Number: 198153‐51‐4 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 180‐ 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‐ CONDITION: chronic hepatitis C infection of genotype 1 ; MedDRA version: 15.0 Level: LLT Classification code 10019751 Term: Hepatitis C virus System Organ Class: 10022891 ‐ Investigations Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: 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; ; Primary end point(s): Part 1: Plasma HCV RNA level <25 IU/mL (detectable or undetectable)* at Week 4; Part 2: Sustained Virological Response (SVR): Plasma HCV RNA not detectable* at 24 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 4 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. Secondary Objective: N.a. 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 20 or week 28 (depending on treatment group) SECONDARY OUTCOME: Secondary end point(s): •Time to virological response: Timepoint of the first measurement of undetectable plasma HCV RNA level ; •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 not detectable at 12 weeks after completion of all therapy ; ; Timepoint(s) of evaluation of this end point: ‐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) 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 and part 3, patients with Child‐Pugh 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