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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01011166
First received: October 2, 2009
Last updated: April 22, 2015
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis C Infection
Drug: IDX184
Drug: Placebo
Biological: Peginterferon alfa-2a (Peg-IFN)
Drug: Ribavirin (RBV)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change in HCV ribonucleic acid (RNA) level from Baseline to Day 15 [ Time Frame: Baseline and Day 15 ] [ Designated as safety issue: No ]
  • Percentage of participants experiencing adverse events (AEs) [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
  • Percentage of participants experiencing serious adverse events (SAEs) [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
  • Percentage of participants experiencing dose-limiting toxicities (DLTs) [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
  • Percentage of participants experiencing Grade 1-4 laboratory abnormalities [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change in HCV RNA level from Baseline to Day 28 [ Time Frame: Baseline and Day 28 ] [ Designated as safety issue: No ]
  • Percentage of participants with undetectable HCV RNA at Day 15 [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • Percentage of participants with undetectable HCV RNA at Day 28 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Percentage of participants experiencing virologic breakthrough while on study therapy [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
  • Change in alanine aminotransferase (ALT) level from Baseline to Day 15 [ Time Frame: Baseline and Day 15 ] [ Designated as safety issue: No ]
  • Change in ALT level from Baseline to Day 28 [ Time Frame: Baseline and Day 28 ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
  • Time to maximum concentration (Tmax) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
  • Area under the drug concentration-time curve (AUC) from time 0 to last measurable concentration (AUC0-t) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
  • AUC from time zero to infinity (AUC0-~) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
  • Trough concentration (Ctrough) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
  • Observed terminal half-life (Thalf) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]

Enrollment: 81
Study Start Date: November 2009
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IDX184 50 mg QD + Peg-IFN/RBV
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
IDX184 50 mg white opaque capsules taken by mouth from Day 1 to Day 14.
Drug: Placebo
Placebo white opaque capsules taken by mouth from Day 1 to Day 14.
Biological: Peginterferon alfa-2a (Peg-IFN)
Peg-IFN was supplied as 180 ug single-use, pre-filled syringes administered once weekly from Day 1 to Day 28.
Other Name: Pegasys
Drug: Ribavirin (RBV)
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.
Experimental: IDX184 100 mg QD + Peg-IFN/RBV
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
IDX184 50 mg white opaque capsules taken by mouth from Day 1 to Day 14.
Drug: Placebo
Placebo white opaque capsules taken by mouth from Day 1 to Day 14.
Biological: Peginterferon alfa-2a (Peg-IFN)
Peg-IFN was supplied as 180 ug single-use, pre-filled syringes administered once weekly from Day 1 to Day 28.
Other Name: Pegasys
Drug: Ribavirin (RBV)
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.
Experimental: IDX184 100 mg BID + Peg-IFN/RBV
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
IDX184 50 mg white opaque capsules taken by mouth from Day 1 to Day 14.
Drug: Placebo
Placebo white opaque capsules taken by mouth from Day 1 to Day 14.
Biological: Peginterferon alfa-2a (Peg-IFN)
Peg-IFN was supplied as 180 ug single-use, pre-filled syringes administered once weekly from Day 1 to Day 28.
Other Name: Pegasys
Drug: Ribavirin (RBV)
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.
Experimental: IDX184 150 mg QD + Peg-IFN/RBV
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
IDX184 50 mg white opaque capsules taken by mouth from Day 1 to Day 14.
Drug: Placebo
Placebo white opaque capsules taken by mouth from Day 1 to Day 14.
Biological: Peginterferon alfa-2a (Peg-IFN)
Peg-IFN was supplied as 180 ug single-use, pre-filled syringes administered once weekly from Day 1 to Day 28.
Other Name: Pegasys
Drug: Ribavirin (RBV)
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.
Experimental: IDX184 200 mg QD + Peg-IFN/RBV
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
IDX184 50 mg white opaque capsules taken by mouth from Day 1 to Day 14.
Drug: Placebo
Placebo white opaque capsules taken by mouth from Day 1 to Day 14.
Biological: Peginterferon alfa-2a (Peg-IFN)
Peg-IFN was supplied as 180 ug single-use, pre-filled syringes administered once weekly from Day 1 to Day 28.
Other Name: Pegasys
Drug: Ribavirin (RBV)
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.
Experimental: IDX184 200 mg BID + Peg-IFN/RBV
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
IDX184 50 mg white opaque capsules taken by mouth from Day 1 to Day 14.
Drug: Placebo
Placebo white opaque capsules taken by mouth from Day 1 to Day 14.
Biological: Peginterferon alfa-2a (Peg-IFN)
Peg-IFN was supplied as 180 ug single-use, pre-filled syringes administered once weekly from Day 1 to Day 28.
Other Name: Pegasys
Drug: Ribavirin (RBV)
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01011166

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01011166     History of Changes
Other Study ID Numbers: 2355-004, IDX-08C-004
Study First Received: October 2, 2009
Last Updated: April 22, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Chronic Hepatitis C
HepC
Hep C

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
RNA Virus Infections
Virus Diseases
Peginterferon alfa-2a
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on July 27, 2015