A Study Evaluating GS-9620 in Virologically Suppressed Subjects With Chronic Hepatitis B Virus Infection
- Conditions
- Hepatitis B
- Interventions
- Drug: Single Ascending Dose (SAD) Cohorts GS-9620Drug: Multiple Ascending Dose (MAD) Cohorts GS-9620
- Registration Number
- NCT01590654
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 51
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 0.3mg GS-9620 Single Ascending Dose (SAD) Cohorts GS-9620 - 1mg GS-9620 Single Ascending Dose (SAD) Cohorts GS-9620 - 2mg GS-9620 Single Ascending Dose (SAD) Cohorts GS-9620 - 4mg GS-9620 Single Ascending Dose (SAD) Cohorts GS-9620 - 0.3mg GS-9620 QW x 2 doses Multiple Ascending Dose (MAD) Cohorts GS-9620 - 4mg GS-9620 QW x 2 doses Multiple Ascending Dose (MAD) Cohorts GS-9620 - 1mg GS-9620 QW x 2 doses Multiple Ascending Dose (MAD) Cohorts GS-9620 - 2mg GS-9620 QW x 2 doses Multiple Ascending Dose (MAD) Cohorts GS-9620 -
- Primary Outcome Measures
Name Time Method Assessment of adverse events in single and multiple oral doses of GS-9620 Periodically Day 1 to 6 months Assessments include adverse events, laboratory abnormalities, 12-lead ECG abnormalities and interval measurements, and vital signs measurements
- Secondary Outcome Measures
Name Time Method Assessment of plasma drug concentrations of GS-9620 using non-compartmental methods Day 1 and Day 8 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.Measurement of pharmacodynamic markers (cytokines and interferon-stimulated genes [ISGs]) Days 1, 2, 3, 5, 8 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 15Reduction of hepatitis B (HBV) viral load from baseline Screening, Baseline, Day 8 or 15 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.
Trial Locations
- Locations (20)
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Algorithme Pharma, Inc.
🇨🇦Laval, Quebec, Canada
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Indiana University Medical Center
🇺🇸Indianapolis, Indiana, United States
Kansas City Gastroenterology and Hepatology
🇺🇸Kansas City, Missouri, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Nepean Hospital, Department of ID
🇦🇺Kingswood, New South Wales, Australia
University of Calgary, Heritage Medical Research Center
🇨🇦Calgary, Alberta, Canada
Alfred Hospital, Department of Gastroenterology
🇦🇺Melbourne, Victoria, Australia
Monash University, Dept. of Medicine
🇦🇺Clayton, Victoria, Australia
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Royal Perth Hospital
🇦🇺Nedlands, Western Australia, Australia
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Aukland Clinical Studies
🇳🇿Grafton, Aukland, New Zealand