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

Sponsor

Gilead Sciences (Industry)

Overall Status

Completed

CT.gov ID

NCT01590641

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

2.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B HBV	Drug: Single Ascending Dose (SAD) Cohorts GS-9620 Drug: Multiple Ascending Dose (MAD) Cohorts	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

49 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Study Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Sep 1, 2013

Actual Study Completion Date :

Oct 1, 2013

Arms and Interventions

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 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 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 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 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)

Outcome Measures

Primary Outcome Measures

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

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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
2	West Coast Clinical Trials, LLC	Costa Mesa	California	United States	92626
3	University of California Antiviral Research Center (AVRC)	San Diego	California	United States	92103
4	Indiana University Medical Center	Indianapolis	Indiana	United States	46202-5121
5	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70122
6	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
7	Henry Ford Health System	Detroit	Michigan	United States	48202
8	Kansas City Gastroenterology and Hepatology	Kansas City	Missouri	United States	64131
9	Weill Cornell Medical College	New York	New York	United States	10021
10	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
11	CRI Worldwide, LLC	Philadelphia	Pennsylvania	United States	19139
12	Baylor College of Medicine	Houston	Texas	United States	77030
13	University of Utah	Salt Lake City	Utah	United States	84123
14	Nepean Hospital	Kingswood	New South Wales	Australia	2747
15	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
16	Monash University, Department of Medicine	Clayton	Victoria	Australia	3168
17	Royal Perth Hospital	Nedlands	Western Australia	Australia	6009
18	University of Calgary, Heritage Medical Research Center	Calgary	Alberta	Canada	T2N 4Z6
19	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
20	Algorithme Pharma, Inc.	Montreal	Quebec	Canada	H3P 3P1
21	Asan Medical Center	Seoul		Korea, Republic of
22	Seoul National University Hospital	Seoul		Korea, Republic of
23	Auckland Clinical Studies	Grafton	Auckland	New Zealand	1142