A Study Evaluating GS-9620 in Treatment Naive Subjects With Chronic Hepatitis C

A Double-Blind, Randomized, Placebo-Controlled, Single and Multiple-Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antiviral Activity of GS-9620 in Treatment Naive Subjects With Chronic Hepatitis C Virus Infection

Dose cohorts may be dosed with one of up to 4 possible total weekly doses (0.3 mg, 1 mg, 2 mg, 4 mg). Dose escalation or repetition will be governed by pre-specified safety and activity rules. Subjects will be confined on either days 1-3 and/or days 8-10. Follow-up visits are also required periodically through day 43. Study procedures involve taking blood samples for pharmacokinetic, pharmacodynamic, virologic, and safety assessments.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Single Ascending Dose Cohorts GS-9620; Drug: Multiple Ascending Dose Cohorts GS-9620

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • Santurce, Puerto Rico, 00909
    • Fundacion de Investigacion de Diego
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Gastroenterology and Hepatology
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Comprehensive Clinical Research
    • Willingboro, New Jersey, United States, 08046
      • CRI Worldwide, LLC
  • New York
    • New York, New York, United States, 10019
      • Clinilabs
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
      • CRI Worldwide, LLC
  • Texas
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Lifetree Clinical Research

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:

• Males and Females 18-65 years old
• Chronic HCV infection for at least 6 months, treatment naive
• HCV Viral load > 100,000 IU/mL at Screening
• Monoinfection with HCV 1 genotype
• Hepatitis B surface antigen negative
• Screening ECG without clinically significant abnormalities
• BMI 18-33 kg/m^2
• Creatinine clearing > 70 mL/min
• Negative pregnancy test at screening

Exclusion Criteria:

• Pregnant or lactating subjects
• Co-infection with hepatitis B virus (HBV) or HIV
• History of Gilberts disease
• Particular abnormal laboratory parameters
• Diagnosis of autoimmune disease, poorly controlled diabetes, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), malignancy, hemoglobinopathy, retinal disease, and those who are immunosuppressed
• Evidence of hepatocellular carcinoma
• On-going alcohol abuse
• Positive uring drug screen

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.3mg GS-9620	Drug: Single Ascending Dose Cohorts GS-9620; This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Dose cohorts may be dosed with one of up to 4 possible total weekly doses (0.3 mg, 1 mg, 2 mg, 4 mg). Subjects in Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.
Experimental: 1mg GS-9620	Drug: Single Ascending Dose Cohorts GS-9620; This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Dose cohorts may be dosed with one of up to 4 possible total weekly doses (0.3 mg, 1 mg, 2 mg, 4 mg). Subjects in Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.
Experimental: 2mg GS-9620	Drug: Single Ascending Dose Cohorts GS-9620; This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Dose cohorts may be dosed with one of up to 4 possible total weekly doses (0.3 mg, 1 mg, 2 mg, 4 mg). Subjects in Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.
Experimental: 4mg GS-9620	Drug: Single Ascending Dose Cohorts GS-9620; This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Dose cohorts may be dosed with one of up to 4 possible total weekly doses (0.3 mg, 1 mg, 2 mg, 4 mg). Subjects in Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.
Experimental: 0.3mg GS-9620 QW x 2 doses	Drug: Multiple Ascending Dose Cohorts GS-9620; This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Subjects in Multiple Ascending Dose (MAD) Cohorts will receive GS-9620 once weekly for two weeks (QW x 2 doses).
Experimental: 1mg GS-9620 QW x 2 doses	Drug: Multiple Ascending Dose Cohorts GS-9620; This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Subjects in Multiple Ascending Dose (MAD) Cohorts will receive GS-9620 once weekly for two weeks (QW x 2 doses).
Experimental: 2mg GS-9620 QW x 2 doses	Drug: Multiple Ascending Dose Cohorts GS-9620; This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Subjects in Multiple Ascending Dose (MAD) Cohorts will receive GS-9620 once weekly for two weeks (QW x 2 doses).
Experimental: 4mg GS-9620 QW x 2 doses	Drug: Multiple Ascending Dose Cohorts GS-9620; This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Subjects in Multiple Ascending Dose (MAD) Cohorts will receive GS-9620 once weekly for two weeks (QW x 2 doses).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events in single and multiple doses of GS-9620	Assessments include adverse events, laboratory abnormalities, 12-lead ECG abnormalities and interval measurements, and vital sign measurements	Periodically Day 1 to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of plasma drug concentrations of GS-9620 using non-compartmental methods	Single ascending dose (SAD) cohorts: serial blood samples will be collected on Day 1 at 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 48, and 96 hours post-dose. Multiple ascending dose (MAD) cohorts: serial blood samples will be collected on Day 8 at 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hours post-dose.	Day 1 and Day 8
Measurement of pharmacodynamic markers (cytokines and interferon-stimulated genes [ISGs])	SAD cohorts: Whole blood and serum for pharmacodynamic (PD) assessments (RNA and cytokine analysis) will be drawn on Day 1: Pre-dose and 8-hour Post-dose, Day 2, Day 3, Day 5, Day 8 MAD cohorts: Whole blood and serum for PD assessments (RNA and cytokine analysis) will be drawn on Day 1: Pre-dose and 8-hours Post-dose, Day 2, Day 3, Day 5, Day 8: Pre-dose and 8 hours Post-dose, Day 9, Day 10, Day 12, and Day 15	Days 1, 2, 3, 5, 8
Reduction of hepatitis C (HCV) RNA viral load from baseline	SAD cohorts: HCV viral load will be drawn at Day 1: Pre-dose, Day 2, 3, 5, 8 and both Follow-up Visits. MAD cohorts: HCV viral load will be drawn at Day 1: Pre-dose, Day 2, 3, 5, Day 8: Pre-dose, 9, 10, 15, and both Follow-Up Visits.	Screening, Baseline, Day 8 or 15

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Lawitz E, Gruener D, Marbury T, Hill J, Webster L, Hassman D, Nguyen AH, Pflanz S, Mogalian E, Gaggar A, Massetto B, Subramanian GM, McHutchison JG, Jacobson IM, Freilich B, Rodriguez-Torres M. Safety, pharmacokinetics and pharmacodynamics of the oral toll-like receptor 7 agonist GS-9620 in treatment-naive patients with chronic hepatitis C. Antivir Ther. 2015;20(7):699-708. doi: 10.3851/IMP2845. Epub 2014 Aug 8.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: March 23, 2012
• First Submitted That Met QC Criteria: May 2, 2012
• First Posted (Estimate): May 4, 2012

Study Record Updates

• Last Update Posted (Estimate): August 13, 2013
• Last Update Submitted That Met QC Criteria: August 12, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: HCV; Hepatitis C; Hepatitis; Treatment Naive; Gilead; Chronic HCV; GS-9620
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Anti-Infective Agents; Antiviral Agents; Vesatolimod
• Other Study ID Numbers: GS-US-243-0102