Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of GS-5816 in Subjects With Chronic HCV Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01740791
First received: November 26, 2012
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

The goal of this study is to assess the safety, tolerability, antiviral activity and pharmacokinetics of GS-5816 in HCV treatment naïve subjects with genotypes 1-6.


Condition Intervention Phase
Chronic Hepatitis C Virus
Drug: GS-5816
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 1b, Randomized, Double-Blind, Multiple-Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of GS-5816 in Subjects With Chronic Hepatitis C Virus Infection

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Safety [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Number of participants with Adverse Events, laboratory abnormalities and ECG abnormalities.

  • Antiviral Activity [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Change from baseline in HCV RNA


Secondary Outcome Measures:
  • Viral Dynamics [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Maximal reduction over time in HCV RNA and proportion of subject with HCV RNA < LLOQ.

  • Characterization of NSA5a coding region in HCV following dose administration of GS-5816 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Sequence changes in the NS5A coding region of HCV following multiple dose administration of GS-5816 and for up to 48 weeks thereafter

  • Pharmacokinetics [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Pharmacokinetics parameters will include Cmax, Tmax, AUC, T1/2

  • Pharmacodynamics [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Changes in HCV NS5A sequence following administration of GS-5816


Enrollment: 94
Study Start Date: November 2012
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
(N = 10, genotype 1a): up to 150 mg GS-5816 or placebo QD fasted for 3 days
Drug: GS-5816
3 days of monotherapy of GS-5816
Experimental: Cohort 2
(N = 10, genotype 1a): up to 150 mg GS-5816 or placebo QD fasted for 3 days
Drug: GS-5816
3 days of monotherapy of GS-5816
Experimental: Cohort 3
(N = 10, genotype 1a): up to 150 mg GS-5816 or placebo QD fasted for 3 days
Drug: GS-5816
3 days of monotherapy of GS-5816
Experimental: Cohort 4
(N = 10, genotype 1a): up to 150 mg GS-5816 or placebo QD fasted for 3 days
Drug: GS-5816
3 days of monotherapy of GS-5816
Experimental: Cohort 5
(N = 10, genotype 2): up to 400 mg GS-5816 or placebo QD fasted for 3 days
Drug: GS-5816
3 days of monotherapy of GS-5816
Experimental: Cohort 6
(N = 10, genotype 2): up to 400 mg GS-5816 or placebo QD fasted for 3 days
Drug: GS-5816
3 days of monotherapy of GS-5816
Experimental: Cohort 7
(N = 10, genotype 3): up to 400 mg GS-5816 or placebo QD fasted for 3 days
Drug: GS-5816
3 days of monotherapy of GS-5816
Experimental: Cohort 8
(N = 10, genotype 4/5/6): up to 400 mg GS-5816 QD fasted for 3 days
Drug: GS-5816
3 days of monotherapy of GS-5816
Experimental: Cohort 9
(N = 10, genotype 1a, 1b, 2, 3 or 4/5/6): up to 400 mg GS-5816 or placebo QD fasted for 3 days
Drug: GS-5816
3 days of monotherapy of GS-5816
Experimental: Cohort 10
(N = 10, genotype 1a, 1b, 2, 3 or 4/5/6): up to 400 mg GS-5816 or placebo QD fasted for 3 days
Drug: GS-5816
3 days of monotherapy of GS-5816
Experimental: Cohort 11
(N = 10, genotype 1a, 1b, 2, 3 or 4/5/6): up to 400 mg GS-5816 or placebo QD fasted for 3 days
Drug: GS-5816
3 days of monotherapy of GS-5816
Experimental: Cohort 12
(N = 10, genotype 1a, 1b, 2, 3 or 4/5/6): up to 400 mg GS-5816 or placebo QD fasted for 3 days
Drug: GS-5816
3 days of monotherapy of GS-5816

Detailed Description:

Administration of GS-5816 will be limited to 3 consecutive days to minimize the potential development of resistance. All subjects will be monitored for up to 48 weeks post-dose to determine the persistence of viral mutations. Twelve cohorts are planned for the examination; within each cohort subjects will receive QD doses of GS-5816 with safety, antiviral activity and pharmacokinetic assessments evaluated at specified time-points during the study

  Eligibility

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

Inclusion Criteria:

  • HCV treatment-naïve adult subjects (18-65 years of age)with chronic HCV infection and plasma HCV RNA ≥ 5 log10 IU/mL at screening
  • Agree to use protocol defined precautions against pregnancy

Exclusion Criteria:

  • Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, α1 antitrypsin deficiency, cholangitis)
  • Evidence of cirrhosis
  • Evidence of current drug abuse
  • Screening laboratory results outside the protocol specified requirements
  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: NCT01740791

Locations
United States, California
West Coast Clinical Trials, LLC
Costa Mesa, California, United States, 92626
United States, Florida
Avail Clinical Research, LLC
Deland, Florida, United States, 32720
Orlando Clinical Research Center
Orlando, Florida, United States, 32809
United States, Missouri
Kansas City Gastroenterology and Hepatology
Kansas City, Missouri, United States, 64131
United States, New Jersey
CRI Worldwide, LLC
Marlton, New Jersey, United States, 08053
United States, Pennsylvania
CRI Worldwide, LLC
Philadelphia, Pennsylvania, United States, 19139
United States, Tennessee
New Orleans Center for Clinical Research-Knoxville
Knoxville, Tennessee, United States, 37920
United States, Texas
Alamo Medical Research
San Antonio, Texas, United States, 78215
United States, Washington
Charles River Clinical Services Northwest, Inc.
Tacoma, Washington, United States, 98418
Puerto Rico
Fundacion De Investigacion De Diego
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: John McNally, PhD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01740791     History of Changes
Other Study ID Numbers: GS-US-281-0102
Study First Received: November 26, 2012
Last Updated: March 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Hepatitis C
HCV
Genotype 1
Genotype 2
Genotype 3
Genotype 4
Genotype 5
Genotype 6
Liver Disease

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 23, 2014