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

Hepatitis B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01590641
• Other study ID #: GS-US-283-0106
• Status: Completed
• Phase: Phase 1
• First received: April 30, 2012
• Last updated: November 13, 2013
• Start date: April 2012
• Est. completion date: October 2013

Study information

• Verified date: November 2013
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaAustralia: Department of Health and Ageing Therapeutic Goods AdministrationNew Zealand: Medsafe
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: October 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• HBV
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

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.
• 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)

Locations

Country	Name	City	State
Australia	Monash University, Department of Medicine	Clayton	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	Royal Perth Hospital	Nedlands	Western Australia
Canada	University of Calgary, Heritage Medical Research Center	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Algorithme Pharma, Inc.	Montreal	Quebec
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
New Zealand	Auckland Clinical Studies	Grafton	Auckland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	West Coast Clinical Trials, LLC	Costa Mesa	California
United States	Henry Ford Health System	Detroit	Michigan
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	Kansas City Gastroenterology and Hepatology	Kansas City	Missouri
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Weill Cornell Medical College	New York	New York
United States	CRI Worldwide, LLC	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	University of Utah	Salt Lake City	Utah
United States	University of California Antiviral Research Center (AVRC)	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Korea, Republic of,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No