Randomized, Controlled Phase 2a/b Study of the Efficacy and Safety of PEG-rIL-29 Administered in Combination with Ribavirin to Treatment-Naive Subjects with Chronic Hepatitis C Virus Infection

INTERVENTION: Product Name: PEG‐rIL‐29 Pharmaceutical Form: Solution for injection CAS Number: 914617‐98‐4 Current Sponsor code: PEG‐rIL‐29 Other descriptive name: PEGylated recombinant IL‐29 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 500‐ Product Name: PEG‐rIL‐29 Pharmaceutical Form: Solution for injection CAS Number: 914617‐98‐4 Current Sponsor code: PEG‐rIL‐29 Other descriptive name: PEGylated recombinant IL‐29 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 200‐ Trade Name: PEGASYS® Product Name: peginterferon alfa‐2a Pharmaceutical Form: Solution for injection INN or Proposed INN: PEGINTERFERON ALFA 2A CAS Number: 198153‐51‐4 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 180‐ Trade Name: RIBASPHERE® 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‐ CONDITION: Chronic Hepatitis C Virus Infection ; MedDRA version: 12.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C INCLUSION CRITERIA: 1. Males or females between the ages of 18 and 70 years, inclusive, at the time of signing informed consent 2. No prior therapy for chronic HCV, other than up to 2 weeks of single‐agent therapy with a direct‐acting antiviral agent, including but not limited to, a protease or polymerase inhibitor 3. Genotype 1, 2, 3, or 4 HCV RNA. Mixed genotype HCV infection is not allowed 4. HCV RNA =100,000 IU/mL 5. ALT and AST =5.0 × ULN 6. Documented absence of cirrhosis, with the exception of approximately 10 subjects per treatment group in Phase 2b. For subjects without cirrhosis, absence of cirrhosis must be documented as follows: genotype 1 and 4 subjects must have a documented liver biopsy performed =2 years before study randomization. Genotype 2 and 3 subjects must have either a documented liver biopsy performed =2 years before study randomization or a FibroTest performed during the screening period. Subjects without cirrhosis must have a documented PRIMARY OUTCOME: Main Objective: Phase 2a ; Part 1 ; The primary objective of Part 1 is to characterize the pharmacokinetics of a single fixed dose of PEG‐rIL‐29 administered subcutaneously (SC) as a single agent at 4 different dose levels in treatment‐naive subjects with chronic hepatitis C virus (HCV) infection. ; ; Part 2; The primary objective in Part 2 is to evaluate the safety and tolerability of repeat dosing for up to 48 weeks with 4 dose levels of PEG‐rIL‐29 administered SC as a fixed dose in combination with ribavirin. ; ; Phase 2b ; The primary objective of Phase 2b is to evaluate the efficacy and safety through Week 12 of up to 4 dose levels, selected from Phase 2a, of PEG‐rIL‐29 administered SC as a fixed dose in combination with ribavirin, compared to peginterferon alfa‐2a administered SC in combination with ribavirin, in treatment‐naive subjects with chronic HCV infection Primary end point(s): Phase 2a: Part 1 Primary endpoint: ; • Serum levels of PEG‐rIL‐29 ; ; Phase 2a: Part 2 Primary endpoint: ; • Overall incidence of dose reductions of PEG‐rIL‐29 and DLTs ; ; Phase 2b Primary endpoints: ; • Efficacy ‐ Proportion of subjects with undetectable HCV RNA at Week 12 (i.e., complete early virologic response [cEVR]) ; ? Safety ‐ Incidence and severity of adverse events through Week 12 Secondary Objective: Phase 2a Part 1: 1. Evaluate the safety and tolerability of a single dose of PEG‐rIL‐29 compared to a single fixed dose of peginterferon alfa‐2a. 2. Evaluate the changes in serum HCV RNA levels over time following a single fixed dose of PEGrIL‐ 29 compared to a single fixed dose of peginterferon alfa‐2a. Part 2: 1. Characterize the pharmacokinetics of repeat doses of PEG‐rIL‐29 administered as a fixed dose in combination with ribavirin. 2. Evaluate the efficacy of repeat dosing with PEG‐rIL‐29 administered as a fixed dose in combination with ribavirin compared to peginterferon alfa‐2a in combination with ribavirin. Phase 2b: 1. Compare the safety and tolerability of PEG‐rIL‐29, (up to 48 weeks) in combination with ribavirin, to peginterferon alfa‐2a in combination with ribavirin. 2. Compare the efficacy of PEG‐rIL‐29, (up to 48 weeks) as a fixed dose over a range of dose levels in combination with ribavirin, to peginterferon alfa‐2a administered with ribavirin.