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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01590641
First received: April 30, 2012
Last updated: November 13, 2013
Last verified: November 2013
  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:


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 ]

    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]) [ Time Frame: Up to Day 15 ] [ Designated as safety issue: No ]

    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 [ 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


Enrollment: 49
Study Start Date: April 2012
Study Completion Date: October 2013
Primary Completion Date: September 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 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
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: NCT01590641

  Show 23 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Benedetta Massetto, M.D. 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 13, 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 B
Hepatitis B, Chronic
Hepatitis, Chronic
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 21, 2014