Safety and Antiviral Activity of IDX184 in Combination With Pegylated Interferon and Ribavirin (MK-2355-004)

Study Overview
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Brief Summary
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This study will assess short term safety, antiviral activity and pharmacokinetics (PK) of IDX184 in combination with Peg-interferon (Peg-IFN)/Ribavirin (RBV) in participants with hepatitis C virus (HCV) genotype (GT) 1 infection. These data will guide dose selection for future, longer term studies.

Official Title
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A Phase II, Randomized, Double-Blind Study to Evaluate the Safety and Antiviral Activity of IDX184 in Combination With Pegylated Interferon and Ribavirin in Subjects With Genotype 1 Chronic Hepatitis C Infection

Conditions
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Chronic Hepatitis C Infection

Intervention / Treatment
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* Drug: IDX184
* Drug: Placebo
* Biological: Peginterferon alfa-2a (Peg-IFN)
* Drug: Ribavirin (RBV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has documented chronic HCV GT1 infection Agrees to use of double-barrier contraception and males agree not to donate sperm from the first dose of study therapy through at least 6 months after the final dose of study therapy Exclusion Criteria: Has received previous antiviral treatment for HCV infection Has cirrhosis or decompensated liver disease Is pregnant or breastfeeding Is co-infected with hepatitis B virus (e.g., hepatitis B surface antigen [HBsAg] positive) and/or human immunodeficiency virus (HIV) Has clinically significant concomitant disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IDX184 50 mg QD + Peg-IFN/RBV<br>Participants randomized 4:1 (active:placebo) to receive IDX184 50 mg or placebo once daily (QD) in combination with Peg-IFN/RBV on Days 14-28 and Peg-IFN/RBV on Days 14-28. | Drug: IDX184<br>* IDX184 50 mg white opaque capsules taken by mouth from Day 1 to Day 14.<br>Drug: Placebo<br>* Placebo white opaque capsules taken by mouth from Day 1 to Day 14.<br>Biological: Peginterferon alfa-2a (Peg-IFN)<br>* Peg-IFN was supplied as 180 ug single-use, pre-filled syringes administered once weekly from Day 1 to Day 28.<br>* Other names: Pegasys;Drug: Ribavirin (RBV)<br>* RBV 200 mg capsules at a total daily dose of 1000 mg to 1200 mg (based on participant body weight) from Day 1 to Day 28.<br>|
| Experimental: IDX184 100 mg QD + Peg-IFN/RBV<br>Participants randomized 4:1 (active:placebo) to receive IDX184 50 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV alone on Days 14-28. | Drug: IDX184<br>* IDX184 50 mg white opaque capsules taken by mouth from Day 1 to Day 14.<br>Drug: Placebo<br>* Placebo white opaque capsules taken by mouth from Day 1 to Day 14.<br>Biological: Peginterferon alfa-2a (Peg-IFN)<br>* Peg-IFN was supplied as 180 ug single-use, pre-filled syringes administered once weekly from Day 1 to Day 28.<br>* Other names: Pegasys;Drug: Ribavirin (RBV)<br>* RBV 200 mg capsules at a total daily dose of 1000 mg to 1200 mg (based on participant body weight) from Day 1 to Day 28.<br>|
| Experimental: IDX184 100 mg BID + Peg-IFN/RBV<br>Participants randomized 4:1 (active:placebo) to receive IDX184 100 mg or placebo twice daily (BID) in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV alone on Days 14-28. | Drug: IDX184<br>* IDX184 50 mg white opaque capsules taken by mouth from Day 1 to Day 14.<br>Drug: Placebo<br>* Placebo white opaque capsules taken by mouth from Day 1 to Day 14.<br>Biological: Peginterferon alfa-2a (Peg-IFN)<br>* Peg-IFN was supplied as 180 ug single-use, pre-filled syringes administered once weekly from Day 1 to Day 28.<br>* Other names: Pegasys;Drug: Ribavirin (RBV)<br>* RBV 200 mg capsules at a total daily dose of 1000 mg to 1200 mg (based on participant body weight) from Day 1 to Day 28.<br>|
| Experimental: IDX184 150 mg QD + Peg-IFN/RBV<br>Participants randomized 4:1 (active:placebo) to receive IDX184 150 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28. | Drug: IDX184<br>* IDX184 50 mg white opaque capsules taken by mouth from Day 1 to Day 14.<br>Drug: Placebo<br>* Placebo white opaque capsules taken by mouth from Day 1 to Day 14.<br>Biological: Peginterferon alfa-2a (Peg-IFN)<br>* Peg-IFN was supplied as 180 ug single-use, pre-filled syringes administered once weekly from Day 1 to Day 28.<br>* Other names: Pegasys;Drug: Ribavirin (RBV)<br>* RBV 200 mg capsules at a total daily dose of 1000 mg to 1200 mg (based on participant body weight) from Day 1 to Day 28.<br>|
| Experimental: IDX184 200 mg QD + Peg-IFN/RBV<br>Participants randomized 4:1 (active:placebo) to receive IDX184 100 mg or placebo QD in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28. | Drug: IDX184<br>* IDX184 50 mg white opaque capsules taken by mouth from Day 1 to Day 14.<br>Drug: Placebo<br>* Placebo white opaque capsules taken by mouth from Day 1 to Day 14.<br>Biological: Peginterferon alfa-2a (Peg-IFN)<br>* Peg-IFN was supplied as 180 ug single-use, pre-filled syringes administered once weekly from Day 1 to Day 28.<br>* Other names: Pegasys;Drug: Ribavirin (RBV)<br>* RBV 200 mg capsules at a total daily dose of 1000 mg to 1200 mg (based on participant body weight) from Day 1 to Day 28.<br>|
| Experimental: IDX184 200 mg BID + Peg-IFN/RBV<br>Participants randomized 4:1 (active:placebo) to receive IDX184 200 mg or placebo BID in combination with Peg-IFN/RBV on Days 1-14 and Peg-IFN/RBV on Days 14-28. | Drug: IDX184<br>* IDX184 50 mg white opaque capsules taken by mouth from Day 1 to Day 14.<br>Drug: Placebo<br>* Placebo white opaque capsules taken by mouth from Day 1 to Day 14.<br>Biological: Peginterferon alfa-2a (Peg-IFN)<br>* Peg-IFN was supplied as 180 ug single-use, pre-filled syringes administered once weekly from Day 1 to Day 28.<br>* Other names: Pegasys;Drug: Ribavirin (RBV)<br>* RBV 200 mg capsules at a total daily dose of 1000 mg to 1200 mg (based on participant body weight) from Day 1 to Day 28.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HCV ribonucleic acid (RNA) level from Baseline to Day 15 |  | Baseline and Day 15 | 
| Percentage of participants experiencing adverse events (AEs) |  | Up to 28 days | 
| Percentage of participants experiencing serious adverse events (SAEs) |  | Up to 28 days | 
| Percentage of participants experiencing dose-limiting toxicities (DLTs) |  | Up to 28 days | 
| Percentage of participants experiencing Grade 1-4 laboratory abnormalities |  | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HCV RNA level from Baseline to Day 28 |  | Baseline and Day 28 | 
| Percentage of participants with undetectable HCV RNA at Day 15 |  | Day 15 | 
| Percentage of participants with undetectable HCV RNA at Day 28 |  | Day 28 | 
| Percentage of participants experiencing virologic breakthrough while on study therapy |  | Up to 28 days | 
| Change in alanine aminotransferase (ALT) level from Baseline to Day 15 |  | Baseline and Day 15 | 
| Change in ALT level from Baseline to Day 28 |  | Baseline and Day 28 | 
| Maximum concentration (Cmax) |  | Up to 28 days | 
| Time to maximum concentration (Tmax) |  | Up to 28 days | 
| Area under the drug concentration-time curve (AUC) from time 0 to last measurable concentration (AUC0-t) |  | Up to 28 days | 
| AUC from time zero to infinity (AUC0- ) |  | Up to 28 days | 
| Trough concentration (Ctrough) |  | Up to 28 days | 
| Observed terminal half-life (Thalf) |  | Up to 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Hepatitis C, HepC, Hep C