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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01590654
First received: April 30, 2012
Last updated: December 18, 2013
Last verified: December 2013
History of Changes
  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 (Subject, Caregiver, 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:

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 ] [ Designated as safety issue: Yes ]
    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 ] [ 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 interferon-stimulated genes [ISGs]) [ Time Frame: Days 1, 2, 3, 5, 8 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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)
Genders Eligible for Study:   Both
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

  Show 20 Study Locations
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
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
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 September 29, 2016