Nonalcoholic Steatohepatitis (NASH)
Conditions
Brief summary
A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of CS0159 in subjects with Non-Alcoholic Steatohepatitis (NASH)
Detailed description
This will be a multicenter, double-blind, randomized, placebo-controlled, dose-ranging study to evaluate the safety, tolerability, PKs, and efficacy of CS0159 in the treatment of patients with NASH over 12 weeks.
Interventions
DRUGCS0159 (Linafexor)
Oral QD
Sponsors
Laboratory Corporation of America
Cascade Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients who meet the diagnosis of NASH. 2. Evidence of metabolic syndrome, except for those patients with biopsy-proven NASH. 3. Body mass index (BMI) \>25 kg/m2, NOTE: for Asian-Americans BMI \>23 kg/m2. 4. Stable use of other antidiabetic, weight loss, or lipid-modifying medications for at least 12 weeks prior to randomization.
Exclusion criteria
1. Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days, whichever is longer. 2. Previous exposure to farnesoid X receptor (FXR) agonists 3 months prior to the first dosing. 3. Current or within 6 months of screening use of drugs associated with steatosis, including but not limited to eg, methotrexate, amiodarone, high-dose estrogen, tamoxifen, long term systemic steroids, anabolic steroids, valproic acid. 4. Prothrombin time international normalized ratio \>1.3, unless due to therapeutic anticoagulation. 5. Total bilirubin \>upper limit of normal (ULN; except for patients with Gilbert's syndrome with a normal direct bilirubin value and normal reticulocyte count). Platelet count \<140 000/mm³, absolute neutrophil count \<1500 cells/mm3, or total 6. white blood cells \<3000 cells/mm3. 7. Alanine aminotransferase and aspartate aminotransferase (AST) \>5 × ULN, or alkaline phosphatase (ALP) \>1.5 × ULN. 8. Weight changes \>10% in 6 months prior to screening, or weight changes \>5% from the screening MRI-PDFF to randomization or from the time of the diagnostic liver biopsy to randomization, whichever is longer. 9. Poorly controlled hypertension (systolic \>160 mm Hg, or diastolic blood pressure \>100 mm Hg - mean of 3 measurements). 10. Uncontrolled diabetes mellitus (hemoglobin A1c \>10.0% during screening).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MRI-PDFF | Week 12 | To assess the changes in liver steatosis through magnetic resonance imaging (MRI) proton density fat fraction (PDFF) from baseline to Week 12 |
| Adverse events | Week 12 | To evaluate the safety and tolerability of CS0159 in patients with NASH treated over 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| t1/2 | week 6, week 12 | half-life (t1/2) from baseline to Week 12 |
| Cmax | week 6, week 12 | maximum concentration (Cmax) from baseline to Week 12 |
| Pharmacodynamics (PD) | week 6, week 12 | Plasma concentrations and PD parameters of the biomarkers of FXR target engagement fibroblast growth factor 19 and 7α-hydroxy-4-cholesten-3-one (C4) from baseline to Week 12 |
| AUC | week 6, week 12 | accumulation ratio of area under the concentration-time curve (AUC) in plasma from baseline to Week 12 |
| tmax | week 6, week 12 | time to maximum plasma concentration (tmax) from baseline to Week 12 |
Countries
United States
Outcome results
None listed