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

Purpose

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

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


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

Assessment of adverse events in single and multiple oral doses of GS-9620 [ Time Frame: Periodically Day 1 to 6 months ]
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 [ Time Frame: Day 1 and Day 8 ]
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]) [ Time Frame: Days 1, 2, 3, 5, 8 ]
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 [ Time Frame: Screening, Baseline, Day 8 or 15 ]
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.


Enrollment:	51
Study Start Date:	April 2012
Study Completion Date:	December 2013
Primary Completion Date:	November 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 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).
Experimental: 1mg GS-9620 QW x 2 doses	Drug: 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).
Experimental: 2mg GS-9620 QW x 2 doses	Drug: 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).
Experimental: 4mg GS-9620 QW x 2 doses	Drug: 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).

Eligibility


Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01590654

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Sponsors and Collaborators

Gilead Sciences

Investigators


Study Director:	Benedetta Massetto, M.D.	Gilead Sciences

More Information


Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01590654 History of Changes
Other Study ID Numbers:	GS-US-283-0102
Study First Received:	April 30, 2012
Last Updated:	December 18, 2013

Keywords provided by Gilead Sciences:


Hepatitis Hepatitis B Hepatitis B Virus	HBV GS-9620 Toll-like receptor (TLR)-7 Agonist

Additional relevant MeSH terms:


Hepatitis Hepatitis A Hepatitis, Chronic Hepatitis B Hepatitis B, Chronic Virus Diseases Liver Diseases	Digestive System Diseases Hepatitis, Viral, Human Enterovirus Infections Picornaviridae Infections RNA Virus Infections Hepadnaviridae Infections DNA Virus Infections

ClinicalTrials.gov processed this record on July 21, 2017