A Multiple Ascending Dose Study of GS 5885 in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Escalating, Multiple, Oral Doses of GS 5885 in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection

The primary purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and activity of escalating, multiple, oral doses of GS-5885 in subjects with chronic genotype 1 Hepatitis C Virus (HCV) infection. Each participant in the study will be sequestered in the clinic for the initial 5 days of the study.

Study Overview

• Status: Completed
• Conditions: HCV Infection
• Intervention / Treatment: Drug: GS-5885; Drug: Placebo; Drug: GS-5885; Drug: GS-5885; Drug: GS-5885

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
    • Cypress, California, United States, 90630
    • National City, California, United States, 91950
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
  • Florida
    • Deland, Florida, United States, 32720
    • Miami, Florida, United States, 33169
    • Orlando, Florida, United States, 32809
  • Missouri
    • St. Louis, Missouri, United States, 63104
  • Oregon
    • Portland, Oregon, United States, 97239
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
  • Texas
    • Houston, Texas, United States, 77030
    • San Antonio, Texas, United States, 78215
  • Washington
    • Tacoma, Washington, United States, 98418

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronically infected with HCV genotype 1
• HCV treatment-naïve
• Not co-infected with HIV or HBV
• HCV RNA viral load of at least 100,000 IU/mL
• BMI 19 to 35 kg/m2
• Subject agrees to use highly effective contraception methods if female of childbearing potential or sexually active male.

Exclusion Criteria:

• History of clinically-significant illness or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
• Decompensated liver disease or cirrhosis or evidence of hepatocellular carcinoma
• Serological evidence of co-infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or another HCV genotype
• Subjects with known, current use of amphetamines and/or cocaine; subjects taking methadone or buprenorphine (opioid replacement therapy) or ongoing alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cohort 1; GS-5885 (3 mg), once daily or matching placebo, once daily	Drug: GS-5885; tablet, oral, 3 mg once daily for 3 days; Drug: Placebo; tablet, oral, once daily for 3 days; Drug: GS-5885; tablet, oral, 10 mg once daily for 3 days; Drug: GS-5885; tablet, oral, 30 mg once daily for 3 days; Drug: GS-5885; tablet, oral, up to 90 mg once daily for 3 days
Active Comparator: Cohort 2; GS-5885 (10 mg), once daily or matching placebo, once daily	Drug: GS-5885; tablet, oral, 3 mg once daily for 3 days; Drug: Placebo; tablet, oral, once daily for 3 days; Drug: GS-5885; tablet, oral, 10 mg once daily for 3 days; Drug: GS-5885; tablet, oral, 30 mg once daily for 3 days; Drug: GS-5885; tablet, oral, up to 90 mg once daily for 3 days
Active Comparator: Cohort 3; GS-5885 (30 mg), once daily or matching placebo, once daily	Drug: GS-5885; tablet, oral, 3 mg once daily for 3 days; Drug: Placebo; tablet, oral, once daily for 3 days; Drug: GS-5885; tablet, oral, 10 mg once daily for 3 days; Drug: GS-5885; tablet, oral, 30 mg once daily for 3 days; Drug: GS-5885; tablet, oral, up to 90 mg once daily for 3 days
Active Comparator: Cohort 4; GS-5885 ( up to 90 mg), once daily or matching placebo, once daily	Drug: GS-5885; tablet, oral, 3 mg once daily for 3 days; Drug: Placebo; tablet, oral, once daily for 3 days; Drug: GS-5885; tablet, oral, 10 mg once daily for 3 days; Drug: GS-5885; tablet, oral, 30 mg once daily for 3 days; Drug: GS-5885; tablet, oral, up to 90 mg once daily for 3 days
Active Comparator: Cohort 5; GS-5885 (up to 90 mg), once daily or matching placebo, once daily	Drug: GS-5885; tablet, oral, 3 mg once daily for 3 days; Drug: Placebo; tablet, oral, once daily for 3 days; Drug: GS-5885; tablet, oral, 10 mg once daily for 3 days; Drug: GS-5885; tablet, oral, 30 mg once daily for 3 days; Drug: GS-5885; tablet, oral, up to 90 mg once daily for 3 days
Active Comparator: Cohort 6 (optional); GS-5885 (up to 90 mg), once daily or matching placebo, once daily	Drug: GS-5885; tablet, oral, 3 mg once daily for 3 days; Drug: Placebo; tablet, oral, once daily for 3 days; Drug: GS-5885; tablet, oral, 10 mg once daily for 3 days; Drug: GS-5885; tablet, oral, 30 mg once daily for 3 days; Drug: GS-5885; tablet, oral, up to 90 mg once daily for 3 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects reporting an adverse event or experiencing a laboratory abnormality	Safety and tolerability assessments will be performed up to Study Day 14 following administration of multiple doses of GS-5885 or placebo for 3 days
Antiviral activity measures: measured by change in plasma HCV RNA levels form baseline	Assessed up to Study Day 14 following administration of multiple doses of GS-5885 or placebo for 3 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Measure of GS-5885 plasma concentration over time	Assessed up to Study Day 14 following administration of multiple doses of GS-5885 or placebo for 3 days
Emergence of viral resistance	Up to 48 weeks following Study Day 14

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Diana Brainard, MD, Gilead Sciences

Publications and helpful links

General Publications

• Wong KA, Worth A, Martin R, Svarovskaia E, Brainard DM, Lawitz E, Miller MD, Mo H. Characterization of Hepatitis C virus resistance from a multiple-dose clinical trial of the novel NS5A inhibitor GS-5885. Antimicrob Agents Chemother. 2013 Dec;57(12):6333-40. doi: 10.1128/AAC.02193-12. Epub 2013 Jul 22.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: August 31, 2010
• First Submitted That Met QC Criteria: August 31, 2010
• First Posted (Estimate): September 2, 2010

Study Record Updates

• Last Update Posted (Estimate): January 21, 2013
• Last Update Submitted That Met QC Criteria: January 18, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Hepatitis C; multiple ascending dose; GS-5885; HCV RNA; NS5A; chronic genotype 1 HCV infection
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Infections; Hepatitis; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Ledipasvir
• Other Study ID Numbers: GS-US-256-0102