A Study Evaluating GS-9620 in Virologically Suppressed Subjects With Chronic Hepatitis B Virus Infection
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| ClinicalTrials.gov Identifier: NCT01590654 |
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Recruitment Status :
Completed
First Posted : May 3, 2012
Last Update Posted : December 20, 2013
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Sponsor:
Gilead Sciences
Information provided by (Responsible Party):
Gilead Sciences
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hepatitis B | Drug: Single Ascending Dose (SAD) Cohorts GS-9620 Drug: Multiple Ascending Dose (MAD) Cohorts GS-9620 | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 51 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (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 |
| Study Start Date : | April 2012 |
| Actual Primary Completion Date : | November 2013 |
| Actual Study Completion Date : | December 2013 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
| 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). |
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.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01590654
Locations
Show 20 study locations
Sponsors and Collaborators
Gilead Sciences
Investigators
| Study Director: | Benedetta Massetto, M.D. | Gilead Sciences |
| Responsible Party: | Gilead Sciences |
| ClinicalTrials.gov Identifier: | NCT01590654 |
| Other Study ID Numbers: |
GS-US-283-0102 |
| First Posted: | May 3, 2012 Key Record Dates |
| Last Update Posted: | December 20, 2013 |
| Last Verified: | December 2013 |
Keywords provided by Gilead Sciences:
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Hepatitis Hepatitis B Hepatitis B Virus |
HBV GS-9620 Toll-like receptor (TLR)-7 Agonist |
Additional relevant MeSH terms:
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Hepatitis A Hepatitis B Hepatitis B, Chronic Virus Diseases Herpesviridae Infections Hepatitis Liver Diseases Digestive System Diseases Hepatitis, Viral, Human |
Enterovirus Infections Picornaviridae Infections RNA Virus Infections Hepadnaviridae Infections DNA Virus Infections Hepatitis, Chronic Vesatolimod Antiviral Agents Anti-Infective Agents |