Hepatitis C
Conditions
Keywords
Hepatitis, Hepatitis C, Chronic HCV, HCV, Treatment Naive, Gilead, GS-9620
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 either days 1-3 and/or days 8-10. Follow-up visits are also required periodically through day 43. Study procedures involve taking blood samples for pharmacokinetic, pharmacodynamic, virologic, and safety assessments.
Interventions
DRUGSingle Ascending Dose 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. Dose cohorts may be dosed with one of up to 4 possible total weekly doses (0.3 mg, 1 mg, 2 mg, 4 mg). Subjects in Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.
DRUGMultiple Ascending Dose 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).
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Males and Females 18-65 years old * Chronic HCV infection for at least 6 months, treatment naive * HCV Viral load \> 100,000 IU/mL at Screening * Monoinfection with HCV 1 genotype * Hepatitis B surface antigen negative * Screening ECG without clinically significant abnormalities * BMI 18-33 kg/m\^2 * Creatinine clearing \> 70 mL/min * Negative pregnancy test at screening
Exclusion criteria
* Pregnant or lactating subjects * Co-infection with hepatitis B virus (HBV) or HIV * History of Gilberts disease * Particular abnormal laboratory parameters * Diagnosis of autoimmune disease, poorly controlled diabetes, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), malignancy, hemoglobinopathy, retinal disease, and those who are immunosuppressed * Evidence of hepatocellular carcinoma * On-going alcohol abuse * Positive uring drug screen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events in single and multiple doses of GS-9620 | Periodically Day 1 to 6 months | Assessments include adverse events, laboratory abnormalities, 12-lead ECG abnormalities and interval measurements, and vital sign measurements |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of plasma drug concentrations of GS-9620 using non-compartmental methods | Day 1 and Day 8 | Single ascending dose (SAD) 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. Multiple ascending dose (MAD) cohorts: serial blood samples will 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]) | Days 1, 2, 3, 5, 8 | SAD cohorts: Whole blood and serum for pharmacodynamic (PD) assessments (RNA and cytokine analysis) will be drawn on Day 1: Pre-dose and 8-hour Post-dose, Day 2, Day 3, Day 5, 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 Post-dose, Day 2, Day 3, Day 5, Day 8: Pre-dose and 8 hours Post-dose, Day 9, Day 10, Day 12, and Day 15 |
| Reduction of hepatitis C (HCV) RNA viral load from baseline | Screening, Baseline, Day 8 or 15 | SAD cohorts: HCV viral load will be drawn at Day 1: Pre-dose, Day 2, 3, 5, 8 and both Follow-up Visits. MAD cohorts: HCV viral load will be drawn at Day 1: Pre-dose, Day 2, 3, 5, Day 8: Pre-dose, 9, 10, 15, and both Follow-Up Visits. |
Countries
Puerto Rico, United States
Outcome results
None listed