A Study Evaluating GS-9620 in Treatment Naive Subjects With Chronic Hepatitis B - 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 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	Intervention	Phase
Hepatitis B HBV	Drug: Single Ascending Dose (SAD) Cohorts GS-9620 Drug: Multiple Ascending Dose (MAD) Cohorts	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B

Drug Information available for: Recombinant Hepatitis B vaccine Hepatitis A Vaccines

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 Through Week 25 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Day 1 and Day 8 ] [ Designated as safety issue: No ]
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 ISGs) [ Time Frame: Up to Day 15 ] [ Designated as safety issue: No ]
SAD Cohorts: whole blood and serum for 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 HBV viral load from baseline [ Time Frame: Up to Day 15 and Follow-Up ] [ Designated as safety issue: No ]
Antiviral activity will be evaluated by determination of HBV HBsAg and HBV viral load kinetics

Estimated Enrollment:	60
Study Start Date:	April 2012
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	July 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 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)

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Chronic HBV infection ≥ 6 months
HBsAg ≥ 250 IU/mL
HBV DNA ≥ 2000 IU/mL at Screening
HBV treatment naïve
Absence of extensive bridging fibrosis (Metavir 3 or greater) or cirrhosis
BMI 18-33 kg/m^2, inclusive
Creatinine clearance ≥ 70 mL/min

Exclusion Criteria:

Co-infection with HCV, HDV, or HIV
History of Gilberts disease
Laboratory parameters not within defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, TSH, or other evidence of hepatic decompensation
Diagnosis of autoimmune disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe COPD, malignancy, hemoglobinopathy, retinal disease, or patients who are immunosuppressed
Evidence of hepatocellular carcinoma

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01590641

Contacts

Contact: Uri Lopatin, MD	650-522-5120	Uri.Lopatin@gilead.com
Contact: Benedetta Massetto, MD	650-522-5075	Benedetta.Massetto@gilead.com

Show 23 Study Locations

Sponsors and Collaborators

Gilead Sciences

More Information

No publications provided

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01590641 History of Changes
Other Study ID Numbers:	GS-US-283-0106
Study First Received:	April 30, 2012
Last Updated:	November 26, 2012
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Australia: Department of Health and Ageing Therapeutic Goods Administration New Zealand: Medsafe

Keywords provided by Gilead Sciences:

Hepatitis
Hepatitis B
Hepatitis B Virus

HBV
GS-9620
TLR-7 Agonist

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Hepatitis, Viral, Human
Liver Diseases

Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections

ClinicalTrials.gov processed this record on May 16, 2013