Liver Fibrosis
Conditions
Keywords
Gilead, Gilead Sciences, GSI, Liver Fibrosis, Liver, Fibrosis
Brief summary
This study will evaluate the safety and tolerability of simtuzumab (GS-6624) in patients with fibrosis of the liver. Up to 20 participants will be enrolled into two sequential cohorts. Cohort 1 will consist of 10 participants who will receive simtuzumab every other week for a total of 3 infusions. Participants in Cohort 2 (10 subjects) will also receive simtuzumab every other week for a total of 3 infusions; the dose will depend on the safety and tolerability of simtuzumab seen in Cohort 1. Participants from both cohorts who have completed the main study will be allowed to continue on simtuzumab treatment for an additional extension period, and will receive up to 13 additional infusions of simtuzumab at a fixed dose of 700 mg for an additional 24 weeks.
Interventions
BIOLOGICALSimtuzumab
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Males and females 18 - 65 years of age * Chronic liver disease of any etiology * Stage 1-3 fibrosis by Metavir score on a liver biopsy. * Body mass index \<36 kg/m2
Exclusion criteria
* Any evidence of hepatic decompensation past or present * Subjects currently abusing amphetamines, cocaine, opiates, or alcohol * Clinically significant cardiac disease * History of cancer, other than non-melanomatous skin cancer, within 5 years prior to Screening * Systemic fungal, bacterial, viral, or other infection that is not controlled * Use of systemic immunosuppressants within 28 days of the Pre-treatment Phase * Use of approved therapy for hepatitis C or hepatitis B virus within 28 days of the Pre-treatment Phase * Pregnant or lactating * History of bleeding diathesis within the last 6 months of study Day 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events on multiple, escalating IV doses of simtuzumab | Through Week 14 | The endpoints to be evaluated will include graded Adverse Events, laboratory abnormalities, and vital sign measurements |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of serum concentration of simtuzumab | Through Week 14 | Trough concentrations will be summarized by day, treatment and dose. |
| Antibody formation to simtuzumab (anti-simtuzumab Abs) | Through Week 14 | Immunogenicity endpoints will be geometric mean titer (GMT) and geometric mean fold rate (GMFR) for a select set of antibodies. |
| Measurement of pharmacodynamic (PD) markers after administration of simtuzumab | Through Week 14 | Pharmacodynamic markers include: Tissue PD markers through mRNA expression, LOXL2, LOX, Other LOXL proteins, αSMA, Collagen 1A1, NFKB1, Caspase 1, SMAD, and NOD; Serum and plasma PD markers include: APRI, LOXL2, Osteopontin, Hyaluronic Acid, CXCL 9, 10 and 11, MMP1, MMP3, MMP9, TIMP1, CD40L, TGF-β1, ET-1, VEGF, GAL3, IL-6 / IL-8 / TNFα / IFNγ, α2-macroglobulin, Apolipoprotein A1. |
| Assessing the effects of chronic dosing of simtuzumab on liver structure and fibrotic markers | Up to 24 weeks | Measuring the effect of an additional 24 weeks of simtuzumab dosing on liver histology, LOXL2 and mRNA expression in the liver and serum markers of liver fibrosis |
Countries
United States
Outcome results
None listed