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

Nonalcoholic Steatohepatitis (NASH) Clinical Trial

Official title:

A Phase II, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of CS0159 in the Treatment of Patients With Nonalcoholic Steatohepatitis (NASH)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05591079
• Other study ID #: NASH-CS0159-002
• Status: Completed
• Phase: Phase 2
• Start date: February 10, 2023
• Est. completion date: November 9, 2023

Study information

• Verified date: July 2023
• Source: Cascade Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of CS0159 in subjects with Non-Alcoholic Steatohepatitis (NASH)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: November 9, 2023
• Est. primary completion date: November 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis (NASH)

Intervention

Drug:
• CS0159 (Linafexor)
Oral QD

Locations

Country	Name	City	State
United States	Texas Liver Institute (TLI) - Austin	Austin	Texas
United States	Oracle Clinical Research	College Park	Georgia
United States	National Research Institute - Gardena	Gardena	California
United States	Raja M. Din MD, PLLC - Gastroenterology & Hepatology	Greenbelt	Maryland
United States	Pioneer Research Solutions Inc - Houston - Stancliff Rd	Houston	Texas
United States	Velocity Clinical Research, Huntington Park	Huntington Park	California
United States	Ocala GI Research	Lady Lake	Florida
United States	Florida Research Institute	Lakewood	Florida
United States	Metropolitan Gastroenterology Associates - Westbank Office and Endoscopy	Marrero	Louisiana
United States	San Marcus Research Clinic, Inc - Miami	Miami	Florida
United States	Floridian Clinical Research, LLC - Miami Lakes	Miami Lakes	Florida
United States	Lucas Research	Morehead City	North Carolina
United States	Gastroenterology Associates of Ocala	Ocala	Florida
United States	Velocity Clinical Research - Panorama City	Panorama City	California
United States	Clinical Trials of Texas, LLC	San Antonio	Texas
United States	The Texas Liver Institute, Inc.	San Antonio	Texas
United States	Velocity Clinical Research - Santa Ana	Santa Ana	California

Sponsors (2)

Lead Sponsor	Collaborator
Cascade Pharmaceuticals, Inc	Laboratory Corporation of America

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MRI-PDFF	To assess the changes in liver steatosis through magnetic resonance imaging (MRI) proton density fat fraction (PDFF) from baseline to Week 12	Week 12
Primary	Adverse events	To evaluate the safety and tolerability of CS0159 in patients with NASH treated over 12 weeks	Week 12
Secondary	Cmax	maximum concentration (Cmax) from baseline to Week 12	week 6, week 12
Secondary	tmax	time to maximum plasma concentration (tmax) from baseline to Week 12	week 6, week 12
Secondary	t1/2	half-life (t1/2) from baseline to Week 12	week 6, week 12
Secondary	AUC	accumulation ratio of area under the concentration-time curve (AUC) in plasma from baseline to Week 12	week 6, week 12
Secondary	Pharmacodynamics (PD)	Plasma concentrations and PD parameters of the biomarkers of FXR target engagement fibroblast growth factor 19 and 7a-hydroxy-4-cholesten-3-one (C4) from baseline to Week 12	week 6, week 12