A Study Evaluating GS-9620 in Virologically Suppressed Subjects With Chronic Hepatitis B Virus Infection

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 Virologically Suppressed 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 days 1-3 and/or days 8-10. Follow-up visits are required periodically through day 43. Subjects with sustained reductions in HbsAg will be requested to return for additional follow-up follow-up visits at 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
• Intervention / Treatment: Drug: Single Ascending Dose (SAD) Cohorts GS-9620; Drug: Multiple Ascending Dose (MAD) Cohorts GS-9620

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

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Hospital, Department of ID
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash University, Dept. of Medicine
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital, Department of Gastroenterology
  • 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
    • Laval, Quebec, Canada, H7V 4B3
      • Algorithme Pharma, Inc.
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
• New Zealand
  • Aukland
    • Grafton, Aukland, New Zealand, 1142
      • Aukland Clinical Studies
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5121
      • Indiana University Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
  • Massachusetts
    • Boston, Massachusetts, United States, 022154
      • 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
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • 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 for ≥ 6 months
• Currently on treatment with at least 1 HBV approved oral drug (i.e. lamivudine, telbivudine, entecavir, adefovir, tenofovir) ≥ 3 months prior to screening
• HBsAg ≥ 250 IU/mL
• HBV DNA at below the level of quantitation (BLQ; to be confirmed at screening)
• 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
• 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 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 (MAD) 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 (MAD) 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 (MAD) 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
Assessment of adverse events in single and multiple oral doses of GS-9620	Assessments include adverse events, laboratory abnormalities, 12-lead ECG abnormalities and interval measurements, and vital signs 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	SAD and 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])	Single ascending dose (SAD) Cohorts: Whole blood and serum for pharmacodynamic (PD) assessments (RNA and cytokine analysis) will be drawn on Day 1 at pre-dose, 8, 24 and 48 hours post-dose, and on Days 5 and Day 8 Multiple ascending dose (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, and Day 5 Day 8: Pre-dose and 8 hours Post-dose, Day 9, 10, 12, and Day 15	Days 1, 2, 3, 5, 8
Reduction of hepatitis B (HBV) viral load from baseline	SAD cohort: HBsAg+ levels will be drawn at Day 1: Pre-dose, Day 2, 3, 5, 8 and both Follow-up Visits. MAD cohorts: HBsAg+ levels 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

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): December 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): December 20, 2013
• Last Update Submitted That Met QC Criteria: December 18, 2013
• Last Verified: December 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; 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; Virus Diseases; Hepatitis B, Chronic; Herpesviridae Infections; Anti-Infective Agents; Antiviral Agents; Vesatolimod
• Other Study ID Numbers: GS-US-283-0102