A Study Evaluating GS-9620 in Treatment Naive Subjects With Chronic Hepatitis B
- Conditions
- Hepatitis BHBV
- Interventions
- Drug: Single Ascending Dose (SAD) Cohorts GS-9620Drug: Multiple Ascending Dose (MAD) Cohorts
- Registration Number
- NCT01590641
- 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 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
- 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
- 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 - 1mg GS-9620 QW x 2 doses Multiple Ascending Dose (MAD) Cohorts - 2mg GS-9620 QW x 2 doses Multiple Ascending Dose (MAD) Cohorts - 4mg GS-9620 QW x 2 doses Multiple Ascending Dose (MAD) Cohorts -
- Primary Outcome Measures
Name Time Method Assessment of adverse events in single and multiple oral doses of GS-9620 Periodically Through Week 25 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.
- Secondary Outcome Measures
Name Time Method Reduction of hepatitis B (HBV) viral load from baseline Up to Day 15 and Follow-Up Antiviral activity will be evaluated by determination of HBV HBsAg and HBV viral load kinetics
Assessment of plasma drug concentrations of GS-9620 using non-compartmental methods Day 1 and Day 8 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.Measurement of pharmacodynamic markers (cytokines and interferon-stimulated genes [ISGs]) Up to Day 15 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
Trial Locations
- Locations (23)
Royal Perth Hospital
🇦🇺Nedlands, Western Australia, Australia
Algorithme Pharma, Inc.
🇨🇦Montreal, Quebec, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
West Coast Clinical Trials, LLC
🇺🇸Costa Mesa, California, United States
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
University of California Antiviral Research Center (AVRC)
🇺🇸San Diego, California, United States
Indiana University Medical Center
🇺🇸Indianapolis, Indiana, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Kansas City Gastroenterology and Hepatology
🇺🇸Kansas City, Missouri, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
Nepean Hospital
🇦🇺Kingswood, New South Wales, Australia
University of Utah
🇺🇸Salt Lake City, Utah, United States
Monash University, Department of Medicine
🇦🇺Clayton, Victoria, Australia
CRI Worldwide, LLC
🇺🇸Philadelphia, Pennsylvania, United States
University of Calgary, Heritage Medical Research Center
🇨🇦Calgary, Alberta, Canada
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Auckland Clinical Studies
🇳🇿Grafton, Auckland, New Zealand
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia