A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of CS0159 in Subjects With NASH

Phase 2

Completed

• Conditions: Nonalcoholic Steatohepatitis (NASH)
• Interventions: Drug: CS0159 (Linafexor)

• Registration Number: NCT05591079
• Lead Sponsor: Cascade Pharmaceuticals, Inc

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.

Study Timeline

• Study First Submitted: 2022-10-09
• Study First Submitted QC: 2022-10-20
• Study First Posted: 2022-10-24
• Study Start: 2023-02-10
• Status Verified: 2023-07
• Primary Completion: 2023-11-09
• Study Completion: 2023-11-09
• Last Update Submitted: 2023-11-20
• Last Update Posted: 2023-11-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 99

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PLACEBO	CS0159 (Linafexor)	One tablet daily for 12 weeks
1.4mg CS0159	CS0159 (Linafexor)	One tablet daily for 12 weeks
2mg CS0159	CS0159 (Linafexor)	One tablet daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
tmax	week 6, week 12	time to maximum plasma concentration (tmax) 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
Cmax	week 6, week 12	maximum concentration (Cmax) from baseline to Week 12
t1/2	week 6, week 12	half-life (t1/2) from baseline to Week 12

Trial Locations

Locations (17)

Floridian Clinical Research, LLC - Miami Lakes; 🇺🇸 Miami Lakes, Florida, United States

Florida Research Institute; 🇺🇸 Lakewood, Florida, United States

San Marcus Research Clinic, Inc - Miami; 🇺🇸 Miami, Florida, United States

Gastroenterology Associates of Ocala; 🇺🇸 Ocala, Florida, United States

Metropolitan Gastroenterology Associates - Westbank Office and Endoscopy; 🇺🇸 Marrero, Louisiana, United States

Velocity Clinical Research - Santa Ana; 🇺🇸 Santa Ana, California, United States

National Research Institute - Gardena; 🇺🇸 Gardena, California, United States

Velocity Clinical Research - Panorama City; 🇺🇸 Panorama City, California, United States

Oracle Clinical Research; 🇺🇸 College Park, Georgia, United States

Lucas Research; 🇺🇸 Morehead City, North Carolina, United States

Texas Liver Institute (TLI) - Austin; 🇺🇸 Austin, Texas, United States

Pioneer Research Solutions Inc - Houston - Stancliff Rd; 🇺🇸 Houston, Texas, United States

The Texas Liver Institute, Inc.; 🇺🇸 San Antonio, Texas, United States

Clinical Trials of Texas, LLC; 🇺🇸 San Antonio, Texas, United States

Ocala GI Research; 🇺🇸 Lady Lake, Florida, United States

Velocity Clinical Research, Huntington Park; 🇺🇸 Huntington Park, California, United States

Raja M. Din MD, PLLC - Gastroenterology & Hepatology; 🇺🇸 Greenbelt, Maryland, United States