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

Hepatitis B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01590654
• Other study ID #: GS-US-283-0102
• Status: Completed
• Phase: Phase 1
• First received: April 30, 2012
• Last updated: December 18, 2013
• Start date: April 2012
• Est. completion date: December 2013

Study information

• Verified date: December 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 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: December 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic
• Virus Diseases

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 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).

Locations

Country	Name	City	State
Australia	Monash University, Dept. of Medicine	Clayton	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Nepean Hospital, Department of ID	Kingswood	New South Wales
Australia	Alfred Hospital, Department of Gastroenterology	Melbourne	Victoria
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.	Laval	Quebec
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
New Zealand	Aukland Clinical Studies	Grafton	Aukland
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	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	Mayo Clinic Hospital	Phoenix	Arizona
United States	University of Utah	Salt Lake City	Utah

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	Assessments include adverse events, laboratory abnormalities, 12-lead ECG abnormalities and interval measurements, and vital signs measurements	Periodically Day 1 to 6 months	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No