Efficacy and Safety Study of PEG-rIL-29 Plus Ribavirin to Treat Chronic Hepatitis C Virus Infection

Study Overview
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Brief Summary
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Interleukin 29 (IL-29) is a substance that is produced in the body to help fight viral infections. The purpose of this study is to evaluate the safety and antiviral effects of several different doses of PEG-rIL-29 (a man-made form of IL-29) when it is given in combination with daily oral doses of ribavirin (an antiviral drug) to subjects with hepatitis C infection who have received no prior treatment for this disease.

Detailed Description
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PEG-rIL-29 (also known as PEG-interferon lambda) is a unique Type III interferon molecule that has demonstrated antiviral activity when administered weekly for 4 weeks to treatment-relapsed and treatment-naive subjects with genotype 1 hepatitis C virus (HCV) infection. Because PEG-rIL-29 binds to a unique receptor with a more limited distribution than the receptor for interferon (IFN)-α, it may have the potential to treat HCV without some of the treatment-limiting side effects associated with IFN-α-based therapies. The purpose of this Phase 2a/b randomized, controlled, multicenter study is to compare the safety and efficacy of PEG-rIL-29 and peginterferon alfa-2a, both administered subcutaneously weekly for up to 48 weeks in combination with daily oral ribavirin, in treatment-naive subjects with chronic genotype 1, 2, 3, or 4 HCV infection. The initial part of the study (Phase 2a) will be conducted as an open-label study; the second part of the study (Phase 2b) will be conducted as a blinded study. The above information provided in this listing is specific to the Phase 2b portion of the study. In addition, two small open-label substudies will be conducted to evaluate the efficacy of 24-week treatment with PEG-rIL-29 and ribavirin in subjects with HCV genotype 1 who have a particular genetic polymorphism associated with favorable response (n=60) and to evaluate the efficacy of 16-week treatment with PEG-rIL-29 and ribavirin in subjects with HCV genotype 2 or 3 (n=30).

Official Title
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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

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: PEG-rIL-29
* Drug: Peginterferon alfa-2a
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 HCV genotype 1, 2, 3, or 4 HCV RNA ≥100,000 IU/mL ALT and AST ≤5.0 × ULN Documented absence of cirrhosis Able to comprehend the investigational nature of this study and sign an informed consent form Exclusion Criteria: Mixed genotype HCV infection Current or prior history of decompensated liver disease Received any investigational drug, including a direct-acting antiviral agent, within 60 days prior to receiving study drug Positive test for hepatitis B surface antigen, human immunodeficiency virus (HIV)-1, or HIV2 antibody at screening Active substance abuse, such as alcohol, or inhaled or injected drugs, within 6 months Additional inclusion and exclusion criteria are specified in the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-rIL-29 at 120 µg<br> | Drug: PEG-rIL-29<br>* Weekly SC injections in combination with ribavirin for up to 48 weeks<br>Drug: Ribavirin<br>* Daily oral administration (400-600 mg BID)<br>|
| Experimental: PEG-rIL-29 at 180 µg<br> | Drug: PEG-rIL-29<br>* Weekly SC injections in combination with ribavirin for up to 48 weeks<br>Drug: Ribavirin<br>* Daily oral administration (400-600 mg BID)<br>|
| Active Comparator: Peginterferon alfa-2a at 180 µg<br> | Drug: Peginterferon alfa-2a<br>* Weekly SC injections in combination with ribavirin for up to 48 weeks<br>* Other names: PEGASYS;Drug: Ribavirin<br>* Daily oral administration (400-600 mg BID)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HCV RNA |  | At week 12, week 24, or week 48 | 
| Incidence and severity of adverse events |  | Through week 12, week 40, or week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events and laboratory abnormalities |  | Up to week 72 | 
| HCV RNA |  | Up to week 72 | 
| PD biomarkers |  | Up to week 72 | 
| Quality of life assessments |  | Up to week 72 | 
| Serum drug concentration profile |  | Up to week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C, Hepatitis C, Chronic, PEGylated recombinant interleukin 29, PEG-interferon lambda, Interleukin 29, Virus, Infection, Liver Diseases