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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)

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ClinicalTrials.gov Identifier: NCT01852604
Recruitment Status : Completed
First Posted : May 14, 2013
Last Update Posted : April 23, 2015
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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 Type : Interventional  (Clinical Trial)
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 : March 2013
Actual Primary Completion Date : April 2015
Actual Study Completion Date : April 2015

Resource links provided by the National Library of Medicine


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.




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

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


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01852604


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Janssen Research & Development, LLC
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01852604     History of Changes
Other Study ID Numbers: 1894-005
IDX-06A-005 ( Other Identifier: Idenix Protocol Number )
First Posted: May 14, 2013    Key Record Dates
Last Update Posted: April 23, 2015
Last Verified: April 2015

Keywords provided by Merck Sharp & Dohme Corp.:
HCV
Hepatitis C
chronic hepatitis C
antiviral

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferons
Ribavirin
Ritonavir
Simeprevir
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors