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

A Double-Blind, Randomized, Placebo-Controlled, Single and Multiple- Dose Ranging, Adaptive Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antiviral Activity of GS-9620 in Treatment Naive Subjects With Chronic Hepatitis B 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 or days 1-3 and 8-10. Follow-up visits are also required periodically through day 43, and potential viral load follow-up visits at weeks 3 and 6 months post last dose. Study procedures involve blood draws for pharmacokinetic, pharmacodynamic, virologic, and safety assessments

Study Overview

• Status: Completed
• Conditions: Hepatitis B; HBV
• Intervention / Treatment: Drug: Single Ascending Dose (SAD) Cohorts GS-9620; Drug: Multiple Ascending Dose (MAD) Cohorts

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash University, Department of Medicine
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Royal Perth Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary, Heritage Medical Research Center
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3P 3P1
      • Algorithme Pharma, Inc.
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1142
      • Auckland Clinical Studies
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
  • California
    • Costa Mesa, California, United States, 92626
      • West Coast Clinical Trials, Llc
    • San Diego, California, United States, 92103
      • University of California Antiviral Research Center (AVRC)
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5121
      • Indiana University Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70122
      • Tulane University Health Sciences Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Gastroenterology and Hepatology
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
      • CRI Worldwide, LLC
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84123
      • University of Utah

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:

• Chronic HBV infection ≥ 6 months
• HBsAg ≥ 250 IU/mL
• HBV treatment naïve
• Absence of extensive bridging fibrosis (Metavir 3 or greater) or cirrhosis
• Creatinine clearance ≥ 70 mL/min

Exclusion Criteria:

• Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), or HIV
• History of Gilberts disease
• Laboratory parameters not within defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, thyroid-stimulating hormone (TSH), or other evidence of hepatic decompensation
• Diagnosis of autoimmune disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease(COPD), malignancy, hemoglobinopathy, retinal disease, or patients who are immunosuppressed
• Evidence of hepatocellular carcinoma

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 (SAD) 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 Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.
Experimental: 1mg GS-9620	Drug: Single Ascending Dose (SAD) 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 Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.
Experimental: 2mg GS-9620	Drug: Single Ascending Dose (SAD) 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 Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.
Experimental: 4mg GS-9620	Drug: Single Ascending Dose (SAD) 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 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 (MAD) Cohorts; 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 (MAD) Cohorts; 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 (MAD) Cohorts; 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 (MAD) Cohorts; 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
Assessment of adverse events in single and multiple oral doses of GS-9620	Safety will be assessed during the study through the reporting of adverse events, by clinical laboratory tests, physical examinations including vital signs and ECGs at various time points during the study, and by documentation of concomitant medications throughout the study.	Periodically Through Week 25

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) and multiple ascending dose (MAD) 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. MAD Cohorts: serial blood samples will also 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-hr post dose, Day 2, Day 3, Days 5 and 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 postdose, Day 2, Day 3, Day 5, and Day 8: pre-dose and 8 hours post-dose, Day 9, Day 10, Day 12, and Day 15	Up to Day 15
Reduction of hepatitis B (HBV) viral load from baseline	Antiviral activity will be evaluated by determination of HBV HBsAg and HBV viral load kinetics	Up to Day 15 and Follow-Up

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: April 30, 2012
• First Submitted That Met QC Criteria: May 2, 2012
• First Posted (Estimate): May 3, 2012

Study Record Updates

• Last Update Posted (Estimate): November 14, 2013
• Last Update Submitted That Met QC Criteria: November 13, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Hepatitis; Hepatitis B; HBV; Hepatitis B Virus; GS-9620; Toll-like receptor (TLR)-7 Agonist
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Anti-Infective Agents; Antiviral Agents; Vesatolimod
• Other Study ID Numbers: GS-US-283-0106