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)

NCT01852604 | Completed Phase 2 DMC

• 2 other identifiers: 1894-005IDX-06A-005
• Study Type: interventional
• Target: 143
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chronic Hepatitis C Virus

Keywords

HCV; Hepatitis C; chronic hepatitis C; antiviral

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• 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

Study Arms (8)

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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; Drug: Simeprevir; Drug: Ribavirin (RBV); Biological: Pegylated interferon (Peg-IFN)

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

EXPERIMENTAL

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; Drug: Simeprevir; Drug: Ribavirin (RBV); Biological: Pegylated interferon (Peg-IFN)

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

EXPERIMENTAL

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; Drug: Simeprevir; Drug: Ribavirin (RBV); Biological: Pegylated interferon (Peg-IFN)

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

EXPERIMENTAL

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; Drug: Simeprevir; Drug: Ribavirin (RBV); Biological: Pegylated interferon (Peg-IFN)

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

EXPERIMENTAL

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; Drug: Simeprevir; Drug: Ribavirin (RBV); Drug: TMC647055; Drug: Ritonavir (RTV); Biological: Pegylated interferon (Peg-IFN)

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

EXPERIMENTAL

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; Drug: Simeprevir; Drug: Ribavirin (RBV); Drug: TMC647055; Drug: Ritonavir (RTV); Biological: Pegylated interferon (Peg-IFN)

Interventions

Samatasvir DRUG

Samatasvir (IDX719) will be supplied as 25 mg and 50 mg oral tablets.

Part A: GT 1b, 4 - samatasvir 100/simeprevir/RBV; Part A: GT 1b, 4 - samatasvir 150/simeprevir/RBV; Part A: GT 1b, 4 - samatasvir 50/simeprevir/RBV; Part B: GT 1b, 4 - samatasvir 100/simeprevir/RBV; Part B: GT 1b, 4 - samatasvir 25/simeprevir/RBV; Part B: GT 6 - samatasvir 100/simeprevir/RBV; Part C: GT 1a, 1b - samatasvir 50/simeprevir/TCM647055/RTV; Part C: GT 1a, 1b - samatasvir 50/simeprivir/TCM647055/RTV/RBV

Simeprevir DRUG

Simeprevir will be supplied as 75 and 150 mg oral capsules.

Part A: GT 1b, 4 - samatasvir 100/simeprevir/RBV; Part A: GT 1b, 4 - samatasvir 150/simeprevir/RBV; Part A: GT 1b, 4 - samatasvir 50/simeprevir/RBV; Part B: GT 1b, 4 - samatasvir 100/simeprevir/RBV; Part B: GT 1b, 4 - samatasvir 25/simeprevir/RBV; Part B: GT 6 - samatasvir 100/simeprevir/RBV; Part C: GT 1a, 1b - samatasvir 50/simeprevir/TCM647055/RTV; Part C: GT 1a, 1b - samatasvir 50/simeprivir/TCM647055/RTV/RBV

Ribavirin (RBV) DRUG

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.

Part A: GT 1b, 4 - samatasvir 100/simeprevir/RBV; Part A: GT 1b, 4 - samatasvir 150/simeprevir/RBV; Part A: GT 1b, 4 - samatasvir 50/simeprevir/RBV; Part B: GT 1b, 4 - samatasvir 100/simeprevir/RBV; Part B: GT 1b, 4 - samatasvir 25/simeprevir/RBV; Part B: GT 6 - samatasvir 100/simeprevir/RBV; Part C: GT 1a, 1b - samatasvir 50/simeprevir/TCM647055/RTV; Part C: GT 1a, 1b - samatasvir 50/simeprivir/TCM647055/RTV/RBV

TMC647055 DRUG

TMC647055 will be supplied as 150 mg oral capsules.

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

Ritonavir (RTV) DRUG

Ritonavir will be supplied as 80 mg/mL oral solution.

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

Pegylated interferon (Peg-IFN) BIOLOGICAL

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.

Part A: GT 1b, 4 - samatasvir 100/simeprevir/RBV; Part A: GT 1b, 4 - samatasvir 150/simeprevir/RBV; Part A: GT 1b, 4 - samatasvir 50/simeprevir/RBV; Part B: GT 1b, 4 - samatasvir 100/simeprevir/RBV; Part B: GT 1b, 4 - samatasvir 25/simeprevir/RBV; Part B: GT 6 - samatasvir 100/simeprevir/RBV; Part C: GT 1a, 1b - samatasvir 50/simeprevir/TCM647055/RTV; Part C: GT 1a, 1b - samatasvir 50/simeprivir/TCM647055/RTV/RBV

Samatasvir matching placebo OTHER

Samatasvir matching placebo will be supplied for the 50 mg tablets used in Part A.

Part A: GT 1b, 4 - samatasvir 100/simeprevir/RBV; Part A: GT 1b, 4 - samatasvir 50/simeprevir/RBV

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Janssen Research & Development, LLC: collaborator

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

samatasvir; Simeprevir; Ribavirin; 27-cyclohexyl-12,13,16,17-tetrahydro-22-methoxy-11,17-dimethyl-10,10-dioxide-2,19-methano-3,7:4,1-dimetheno-1H,11H-14,10,2,9,11,17-benzoxathiatetraazacyclo docosine-8,18(9H,15H)-dione; Ritonavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2013
• First Posted: May 14, 2013
• Study Start: March 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: April 23, 2015

Record last verified: 2015-04