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)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis C Virus

Treatments: Drug: Simeprevir; Drug: TMC647055; Drug: Ritonavir (RTV); Biological: Pegylated interferon (Peg-IFN); Other: Samatasvir matching placebo; Drug: Ribavirin (RBV); Drug: Samatasvir

Study type: Interventional

Funder types: Industry

Identifiers

NCT01852604

IDX-06A-005 (Other Identifier)

1894-005

Details and patient eligibility

About

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.

Full description

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

Enrollment: 143 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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143 participants in 8 patient groups

Part A: GT 1b, 4 - samatasvir 50/simeprevir/RBV

Experimental group

Description:

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

Treatment:

Drug: Simeprevir

Other: Samatasvir matching placebo

Drug: Ribavirin (RBV)

Drug: Samatasvir

Biological: Pegylated interferon (Peg-IFN)

Part A: GT 1b, 4 - samatasvir 100/simeprevir/RBV

Experimental group

Description:

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

Treatment:

Drug: Simeprevir

Other: Samatasvir matching placebo

Drug: Ribavirin (RBV)

Drug: Samatasvir

Biological: Pegylated interferon (Peg-IFN)

Part A: GT 1b, 4 - samatasvir 150/simeprevir/RBV

Experimental group

Description:

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

Treatment:

Drug: Simeprevir

Drug: Ribavirin (RBV)

Drug: Samatasvir

Biological: Pegylated interferon (Peg-IFN)

Part B: GT 1b, 4 - samatasvir 25/simeprevir/RBV

Experimental group

Description:

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

Treatment:

Drug: Simeprevir

Drug: Ribavirin (RBV)

Drug: Samatasvir

Biological: Pegylated interferon (Peg-IFN)

Part B: GT 1b, 4 - samatasvir 100/simeprevir/RBV

Experimental group

Description:

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

Treatment:

Drug: Simeprevir

Drug: Ribavirin (RBV)

Drug: Samatasvir

Biological: Pegylated interferon (Peg-IFN)

Part B: GT 6 - samatasvir 100/simeprevir/RBV

Experimental group

Description:

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

Treatment:

Drug: Simeprevir

Drug: Ribavirin (RBV)

Drug: Samatasvir

Biological: Pegylated interferon (Peg-IFN)

Part C: GT 1a, 1b - samatasvir 50/simeprevir/TCM647055/RTV

Experimental group

Description:

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

Treatment:

Drug: Simeprevir

Drug: Ribavirin (RBV)

Drug: TMC647055

Drug: Ritonavir (RTV)

Drug: Samatasvir

Biological: Pegylated interferon (Peg-IFN)

Part C: GT 1a, 1b - samatasvir 50/simeprivir/TCM647055/RTV/RBV

Experimental group

Description:

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

Treatment:

Drug: Simeprevir

Drug: Ribavirin (RBV)

Drug: TMC647055

Drug: Ritonavir (RTV)

Drug: Samatasvir

Biological: Pegylated interferon (Peg-IFN)