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

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)

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

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Drug: CS0159 (Linafexor)

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 Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Gardena, California, United States, 90247-3586
      • National Research Institute - Gardena
    • Huntington Park, California, United States, 90255-2959
      • Velocity Clinical Research, Huntington Park
    • Panorama City, California, United States, 91402-3022
      • Velocity Clinical Research - Panorama City
    • Santa Ana, California, United States, 92704
      • Velocity Clinical Research - Santa Ana
  • Florida
    • Lady Lake, Florida, United States, 32159
      • Ocala GI Research
    • Lakewood, Florida, United States, 34211-4930
      • Florida Research Institute
    • Miami, Florida, United States, 33014-5602
      • San Marcus Research Clinic, Inc - Miami
    • Miami Lakes, Florida, United States, 33016-1518
      • Floridian Clinical Research, LLC - Miami Lakes
    • Ocala, Florida, United States, 34471
      • Gastroenterology Associates of Ocala
  • Georgia
    • College Park, Georgia, United States, 30349
      • Oracle Clinical Research
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Metropolitan Gastroenterology Associates - Westbank Office and Endoscopy
  • Maryland
    • Greenbelt, Maryland, United States, 20770-6702
      • Raja M. Din MD, PLLC - Gastroenterology & Hepatology
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research
  • Texas
    • Austin, Texas, United States, 78757-7571
      • Texas Liver Institute (TLI) - Austin
    • Houston, Texas, United States, 77099-4307
      • Pioneer Research Solutions Inc - Houston - Stancliff Rd
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, LLC
    • San Antonio, Texas, United States, 78215
      • The Texas Liver Institute, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1.4mg CS0159; One tablet daily for 12 weeks	Drug: CS0159 (Linafexor); Oral QD; Other Names: placebo
Experimental: 2mg CS0159; One tablet daily for 12 weeks	Drug: CS0159 (Linafexor); Oral QD; Other Names: placebo
Placebo Comparator: PLACEBO; One tablet daily for 12 weeks	Drug: CS0159 (Linafexor); Oral QD; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Adverse events	To evaluate the safety and tolerability of CS0159 in patients with NASH treated over 12 weeks	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	maximum concentration (Cmax) from baseline to Week 12	week 6, week 12
tmax	time to maximum plasma concentration (tmax) from baseline to Week 12	week 6, week 12
t1/2	half-life (t1/2) from baseline to Week 12	week 6, week 12
AUC	accumulation ratio of area under the concentration-time curve (AUC) in plasma from baseline to Week 12	week 6, week 12
Pharmacodynamics (PD)	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	week 6, week 12

Collaborators and Investigators

• Sponsor: Cascade Pharmaceuticals, Inc
• Collaborators: Laboratory Corporation of America
• Investigators: Study Director: Rong Deng, Cascade Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2023
• Primary Completion (Actual): November 9, 2023
• Study Completion (Actual): November 9, 2023

Study Registration Dates

• First Submitted: October 9, 2022
• First Submitted That Met QC Criteria: October 20, 2022
• First Posted (Actual): October 24, 2022

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: NASH-CS0159-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No