Samatasvir (IDX719) in Combinations With Simeprevir and/or TMC647055/Ritonavir With or Without Ribavirin for 12 Weeks in Participants With Chronic Hepatitis C Infection (MK-1894-005)

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT01852604

Collaborator

Janssen Research & Development, LLC (Industry)

143

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

Parts A and B of this study are designed to evaluate the safety, tolerability, efficacy and pharmacokinetic profiles of samatasvir and simeprevir when administered in combination with ribavirin (RBV) for 12 weeks in treatment-naïve, Genotype (GT) 1b, 4 and 6 hepatitic C virus (HCV)-infected participants.

Part C of this study is designed to evaluate the safety, tolerability, efficacy and pharmacokinetic profiles of samatasvir, simeprevir, TMC647055 and ritonavir (RTV) when administered in combination with or without RBV for 12 weeks in treatment-naïve or interferon/RBV-treatment relapsed, GT 1a and 1b HCV-infected participants.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Virus	Drug: Samatasvir Drug: Simeprevir Drug: Ribavirin (RBV) Drug: TMC647055 Drug: Ritonavir (RTV) Biological: Pegylated interferon (Peg-IFN) Other: Samatasvir matching placebo	Phase 2

Detailed Description

Part A of this study is randomized and double-blind. Parts B and C are randomized and open-label.

Study Design

Study Type:

Interventional

Actual Enrollment :

143 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized Study to Evaluate the Safety and Efficacy of IDX719 in Combinations With Simeprevir and/or TMC647055/Ritonavir With or Without Ribavirin for 12 Weeks in Subjects With Chronic Hepatitis C Infection

Study Start Date :

Mar 1, 2013

Actual Primary Completion Date :

Apr 1, 2015

Actual Study Completion Date :

Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: GT 1b, 4 - samatasvir 50/simeprevir/RBV Part A: Participants with genotype 1b or 4 received samatasvir 50 mg and samatasvir matching placebo once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks	Drug: Samatasvir Samatasvir (IDX719) will be supplied as 25 mg and 50 mg oral tablets. Drug: Simeprevir Simeprevir will be supplied as 75 and 150 mg oral capsules. Drug: Ribavirin (RBV) Ribavirin will be supplied as 200 mg oral tablets. Participants in the RBV-free arms experiencing non-response or virologic breakthrough during the treatment period will be offered RBV dosed according to the product label as an add-on to the participant's randomized treatment assignment. Biological: Pegylated interferon (Peg-IFN) Participants experiencing non-response or virologic breakthrough during the treatment period will be offered Peg-IFN (subcutaneous injection) dosed according to the product label as an add-on to the participant's randomized treatment assignment. Other: Samatasvir matching placebo Samatasvir matching placebo will be supplied for the 50 mg tablets used in Part A.
Experimental: Part A: GT 1b, 4 - samatasvir 100/simeprevir/RBV Part A: Participants with genotype 1b or 4 received samatasvir 100 mg and samatasvir matching placebo once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks	Drug: Samatasvir Samatasvir (IDX719) will be supplied as 25 mg and 50 mg oral tablets. Drug: Simeprevir Simeprevir will be supplied as 75 and 150 mg oral capsules. Drug: Ribavirin (RBV) Ribavirin will be supplied as 200 mg oral tablets. Participants in the RBV-free arms experiencing non-response or virologic breakthrough during the treatment period will be offered RBV dosed according to the product label as an add-on to the participant's randomized treatment assignment. Biological: Pegylated interferon (Peg-IFN) Participants experiencing non-response or virologic breakthrough during the treatment period will be offered Peg-IFN (subcutaneous injection) dosed according to the product label as an add-on to the participant's randomized treatment assignment. Other: Samatasvir matching placebo Samatasvir matching placebo will be supplied for the 50 mg tablets used in Part A.
Experimental: Part A: GT 1b, 4 - samatasvir 150/simeprevir/RBV Part A: Participants with genotype 1b or 4 received samatasvir 150 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks	Drug: Samatasvir Samatasvir (IDX719) will be supplied as 25 mg and 50 mg oral tablets. Drug: Simeprevir Simeprevir will be supplied as 75 and 150 mg oral capsules. Drug: Ribavirin (RBV) Ribavirin will be supplied as 200 mg oral tablets. Participants in the RBV-free arms experiencing non-response or virologic breakthrough during the treatment period will be offered RBV dosed according to the product label as an add-on to the participant's randomized treatment assignment. Biological: Pegylated interferon (Peg-IFN) Participants experiencing non-response or virologic breakthrough during the treatment period will be offered Peg-IFN (subcutaneous injection) dosed according to the product label as an add-on to the participant's randomized treatment assignment.
Experimental: Part B: GT 1b, 4 - samatasvir 25/simeprevir/RBV Part B: Participants with genotype 1b or 4 received samatasvir 25 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks	Drug: Samatasvir Samatasvir (IDX719) will be supplied as 25 mg and 50 mg oral tablets. Drug: Simeprevir Simeprevir will be supplied as 75 and 150 mg oral capsules. Drug: Ribavirin (RBV) Ribavirin will be supplied as 200 mg oral tablets. Participants in the RBV-free arms experiencing non-response or virologic breakthrough during the treatment period will be offered RBV dosed according to the product label as an add-on to the participant's randomized treatment assignment. Biological: Pegylated interferon (Peg-IFN) Participants experiencing non-response or virologic breakthrough during the treatment period will be offered Peg-IFN (subcutaneous injection) dosed according to the product label as an add-on to the participant's randomized treatment assignment.
Experimental: Part B: GT 1b, 4 - samatasvir 100/simeprevir/RBV Part B: Participants with genotype 1b or 4 received samatasvir 100 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks	Drug: Samatasvir Samatasvir (IDX719) will be supplied as 25 mg and 50 mg oral tablets. Drug: Simeprevir Simeprevir will be supplied as 75 and 150 mg oral capsules. Drug: Ribavirin (RBV) Ribavirin will be supplied as 200 mg oral tablets. Participants in the RBV-free arms experiencing non-response or virologic breakthrough during the treatment period will be offered RBV dosed according to the product label as an add-on to the participant's randomized treatment assignment. Biological: Pegylated interferon (Peg-IFN) Participants experiencing non-response or virologic breakthrough during the treatment period will be offered Peg-IFN (subcutaneous injection) dosed according to the product label as an add-on to the participant's randomized treatment assignment.
Experimental: Part B: GT 6 - samatasvir 100/simeprevir/RBV Part B: Participants with Genotype 6 received samatasvir 100 mg once daily, plus simeprevir 150 mg capsule once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks	Drug: Samatasvir Samatasvir (IDX719) will be supplied as 25 mg and 50 mg oral tablets. Drug: Simeprevir Simeprevir will be supplied as 75 and 150 mg oral capsules. Drug: Ribavirin (RBV) Ribavirin will be supplied as 200 mg oral tablets. Participants in the RBV-free arms experiencing non-response or virologic breakthrough during the treatment period will be offered RBV dosed according to the product label as an add-on to the participant's randomized treatment assignment. Biological: Pegylated interferon (Peg-IFN) Participants experiencing non-response or virologic breakthrough during the treatment period will be offered Peg-IFN (subcutaneous injection) dosed according to the product label as an add-on to the participant's randomized treatment assignment.
Experimental: Part C: GT 1a, 1b - samatasvir 50/simeprevir/TCM647055/RTV Part C: Participants with Genotype 1a or 1b received samatasvir 50 mg once daily, plus simeprevir 75 mg capsule once daily, plus TMC647055 450 mg once daily plus RTV 30 mg once daily for 12 weeks	Drug: Samatasvir Samatasvir (IDX719) will be supplied as 25 mg and 50 mg oral tablets. Drug: Simeprevir Simeprevir will be supplied as 75 and 150 mg oral capsules. Drug: Ribavirin (RBV) Ribavirin will be supplied as 200 mg oral tablets. Participants in the RBV-free arms experiencing non-response or virologic breakthrough during the treatment period will be offered RBV dosed according to the product label as an add-on to the participant's randomized treatment assignment. Drug: TMC647055 TMC647055 will be supplied as 150 mg oral capsules. Drug: Ritonavir (RTV) Ritonavir will be supplied as 80 mg/mL oral solution. Biological: Pegylated interferon (Peg-IFN) Participants experiencing non-response or virologic breakthrough during the treatment period will be offered Peg-IFN (subcutaneous injection) dosed according to the product label as an add-on to the participant's randomized treatment assignment.
Experimental: Part C: GT 1a, 1b - samatasvir 50/simeprivir/TCM647055/RTV/RBV Part C: Participants with Genotype 1a or 1b received samatasvir 50 mg once daily, plus simeprevir 75 mg capsule once daily, plus TMC647055 450 mg once daily, plus RTV 30 mg once daily, plus RBV (dosing weight-based, according to product label) twice daily for 12 weeks	Drug: Samatasvir Samatasvir (IDX719) will be supplied as 25 mg and 50 mg oral tablets. Drug: Simeprevir Simeprevir will be supplied as 75 and 150 mg oral capsules. Drug: Ribavirin (RBV) Ribavirin will be supplied as 200 mg oral tablets. Participants in the RBV-free arms experiencing non-response or virologic breakthrough during the treatment period will be offered RBV dosed according to the product label as an add-on to the participant's randomized treatment assignment. Drug: TMC647055 TMC647055 will be supplied as 150 mg oral capsules. Drug: Ritonavir (RTV) Ritonavir will be supplied as 80 mg/mL oral solution. Biological: Pegylated interferon (Peg-IFN) Participants experiencing non-response or virologic breakthrough during the treatment period will be offered Peg-IFN (subcutaneous injection) dosed according to the product label as an add-on to the participant's randomized treatment assignment.

Outcome Measures

Primary Outcome Measures

Percentage of participants who experienced an adverse event (AE) [Up to approximately 95 weeks]
Percentage of participants who experienced a serious adverse event (SAE) [Up to approximately 95 weeks]
Percentage of participants who experienced a Grade 1-4 laboratory abnormality [Up to 66 weeks]
Percentage of participants who experienced sustained virologic response 4 weeks after the end of treatment (SVR4) [Up to 16 weeks]

Secondary Outcome Measures

Percentage of participants who experienced rapid virologic response (RVR) [Week 4]
Percentage of participants who experienced early virologic response (EVR) [Week 12]
Percentage of participants who experienced sustained virologic response 8 weeks after the end of treatment (SVR8) [Up to 20 weeks]
Percentage of participants who experienced sustained virologic response 12 weeks after the end of treatment (SVR12) [Up to 24 weeks]
Percentage of participants who experienced sustained virologic response 24 weeks after the end of treatment (SVR24) [Up to 36 weeks]
Pharmacokinetic Parameter:Area under the concentration-time curve from time zero to t [Days 1, 4, 7, 10, 14, 21, 28, 42, 56 and 84]
Pharmacokinetic Parameter: Maximum observed drug concentration (Cmax) [Days 1, 4, 7, 10, 14, 21, 28, 42, 56 and 84]
Pharmacokinetic Parameter: Trough drug concentration (Ctrough) [Days 1, 4, 7, 10, 14, 21, 28, 42, 56 and 84]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must have Genotype 1a, 1b, 4 or 6 HCV infection.
Documented clinical history compatible with chronic hepatitis C
HCV treatment-naïve or interferon/RBV-treatment relapsed (Part C)
Must agree to use an acceptable double method of birth control (one of which must be a barrier method) for at least 6 months after the last dose of study drugs.

Exclusion Criteria:

Female participants who are pregnant or breastfeeding.
Body Mass Index (BMI) > 36 kg/m2.
Co-infected with hepatitis B virus or human immunodeficiency virus (HIV).
History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC.
History or signs of decompensated liver disease: ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or other clinical signs of portal hypertension or hepatic insufficiency.
Has one or more known primary or secondary causes of liver disease, other than hepatitis C
History of, or active, acute or chronic, liver or biliary injury due to drugs, toxins, non-HCV viral hepatitis, gallstones or other etiologies
Donated blood or had significant blood loss 30 days prior to dosing