Back to resultsA Study Evaluating GS-9620 in Virologically Suppressed Subjects With Chronic Hepatitis B Virus Infection
Primary Purpose
Hepatitis B
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Single Ascending Dose (SAD) Cohorts GS-9620
Multiple Ascending Dose (MAD) Cohorts GS-9620
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis B focused on measuring Hepatitis, Hepatitis B, Hepatitis B Virus, HBV, GS-9620, Toll-like receptor (TLR)-7 Agonist
Eligibility Criteria
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
Sites / Locations
- Mayo Clinic Hospital
- Indiana University Medical Center
- Tulane University Health Sciences Center
- Beth Israel Deaconess Medical Center
- Henry Ford Health System
- Kansas City Gastroenterology and Hepatology
- Weill Cornell Medical College
- Baylor College of Medicine
- University of Utah
- Nepean Hospital, Department of ID
- Royal Brisbane and Women's Hospital
- Monash University, Dept. of Medicine
- Alfred Hospital, Department of Gastroenterology
- Royal Perth Hospital
- University of Calgary, Heritage Medical Research Center
- University of Alberta Hospital
- Algorithme Pharma, Inc.
- Asan Medical Center
- Seoul National University Hospital
- Aukland Clinical Studies
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
0.3mg GS-9620
1mg GS-9620
2mg GS-9620
4mg GS-9620
0.3mg GS-9620 QW x 2 doses
1mg GS-9620 QW x 2 doses
2mg GS-9620 QW x 2 doses
4mg GS-9620 QW x 2 doses
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01590654
Brief Title
A Study Evaluating GS-9620 in Virologically Suppressed Subjects With Chronic Hepatitis B Virus Infection
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Data Monitoring Committee
Yes
5. 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 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B
Keywords
Hepatitis, Hepatitis B, Hepatitis B Virus, HBV, GS-9620, Toll-like receptor (TLR)-7 Agonist
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
0.3mg GS-9620
Arm Type
Experimental
Arm Title
1mg GS-9620
Arm Type
Experimental
Arm Title
2mg GS-9620
Arm Type
Experimental
Arm Title
4mg GS-9620
Arm Type
Experimental
Arm Title
0.3mg GS-9620 QW x 2 doses
Arm Type
Experimental
Arm Title
1mg GS-9620 QW x 2 doses
Arm Type
Experimental
Arm Title
2mg GS-9620 QW x 2 doses
Arm Type
Experimental
Arm Title
4mg GS-9620 QW x 2 doses
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Single Ascending Dose (SAD) Cohorts GS-9620
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Multiple Ascending Dose (MAD) Cohorts GS-9620
Intervention Description
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).
Primary Outcome Measure Information:
Title
Assessment of adverse events in single and multiple oral doses of GS-9620
Description
Assessments include adverse events, laboratory abnormalities, 12-lead ECG abnormalities and interval measurements, and vital signs measurements
Time Frame
Periodically Day 1 to 6 months
Secondary Outcome Measure Information:
Title
Assessment of plasma drug concentrations of GS-9620 using non-compartmental methods
Description
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.
Time Frame
Day 1 and Day 8
Title
Measurement of pharmacodynamic markers (cytokines and interferon-stimulated genes [ISGs])
Description
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
Time Frame
Days 1, 2, 3, 5, 8
Title
Reduction of hepatitis B (HBV) viral load from baseline
Description
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.
Time Frame
Screening, Baseline, Day 8 or 15
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benedetta Massetto, M.D.
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Indiana University Medical Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5121
Country
United States
Facility Name
Tulane University Health Sciences Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
022154
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Kansas City Gastroenterology and Hepatology
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64131
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Nepean Hospital, Department of ID
City
Kingswood
State/Province
New South Wales
ZIP/Postal Code
2747
Country
Australia
Facility Name
Royal Brisbane and Women's Hospital
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Monash University, Dept. of Medicine
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Alfred Hospital, Department of Gastroenterology
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Royal Perth Hospital
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
University of Calgary, Heritage Medical Research Center
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
Facility Name
University of Alberta Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
Algorithme Pharma, Inc.
City
Laval
State/Province
Quebec
ZIP/Postal Code
H7V 4B3
Country
Canada
Facility Name
Asan Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Aukland Clinical Studies
City
Grafton
State/Province
Aukland
ZIP/Postal Code
1142
Country
New Zealand
12. IPD Sharing Statement
Learn more about this trial
A Study Evaluating GS-9620 in Virologically Suppressed Subjects With Chronic Hepatitis B Virus Infection
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