Back to resultsA Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of CS0159 in Subjects With NASH
Primary Purpose
Nonalcoholic Steatohepatitis (NASH)
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CS0159 (Linafexor)
Sponsored by
About this trial
This is an interventional treatment trial for Nonalcoholic Steatohepatitis (NASH)
Eligibility Criteria
Inclusion Criteria:
- Patients who meet the diagnosis of NASH.
- Evidence of metabolic syndrome, except for those patients with biopsy-proven NASH.
- Body mass index (BMI) >25 kg/m2, NOTE: for Asian-Americans BMI >23 kg/m2.
- Stable use of other antidiabetic, weight loss, or lipid-modifying medications for at least 12 weeks prior to randomization.
Exclusion Criteria:
- Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days, whichever is longer.
- Previous exposure to farnesoid X receptor (FXR) agonists 3 months prior to the first dosing.
- 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.
- Prothrombin time international normalized ratio >1.3, unless due to therapeutic anticoagulation.
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
- white blood cells <3000 cells/mm3.
- Alanine aminotransferase and aspartate aminotransferase (AST) >5 × ULN, or alkaline phosphatase (ALP) >1.5 × ULN.
- 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.
- Poorly controlled hypertension (systolic >160 mm Hg, or diastolic blood pressure >100 mm Hg - mean of 3 measurements).
- Uncontrolled diabetes mellitus (hemoglobin A1c >10.0% during screening).
Sites / Locations
- National Research Institute - Gardena
- Velocity Clinical Research, Huntington Park
- Velocity Clinical Research - Panorama City
- Velocity Clinical Research - Santa Ana
- Ocala GI Research
- Florida Research Institute
- Floridian Clinical Research, LLC - Miami Lakes
- San Marcus Research Clinic, Inc - Miami
- Gastroenterology Associates of Ocala
- Oracle Clinical Research
- Metropolitan Gastroenterology Associates - Westbank Office and Endoscopy
- Raja M. Din MD, PLLC - Gastroenterology & Hepatology
- Lucas Research
- Texas Liver Institute (TLI) - Austin
- Pioneer Research Solutions Inc - Houston - Stancliff Rd
- The Texas Liver Institute, Inc.
- Clinical Trials of Texas, LLC
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
1.4mg CS0159
2mg CS0159
PLACEBO
Arm Description
One tablet daily for 12 weeks
One tablet daily for 12 weeks
One tablet daily for 12 weeks
Outcomes
Primary Outcome Measures
MRI-PDFF
To assess the changes in liver steatosis through magnetic resonance imaging (MRI) proton density fat fraction (PDFF) from baseline to Week 12
Adverse events
To evaluate the safety and tolerability of CS0159 in patients with NASH treated over 12 weeks
Secondary Outcome Measures
Cmax
maximum concentration (Cmax) from baseline to Week 12
tmax
time to maximum plasma concentration (tmax) from baseline to Week 12
t1/2
half-life (t1/2) from baseline to Week 12
AUC
accumulation ratio of area under the concentration-time curve (AUC) in plasma from baseline to 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
Full Information
NCT ID
NCT05591079
First Posted
October 9, 2022
Last Updated
July 25, 2023
Sponsor
Cascade Pharmaceuticals, Inc
Collaborators
Laboratory Corporation of America
1. Study Identification
Unique Protocol Identification Number
NCT05591079
Brief Title
A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of CS0159 in Subjects With NASH
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)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 10, 2023 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
November 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cascade Pharmaceuticals, Inc
Collaborators
Laboratory Corporation of America
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonalcoholic Steatohepatitis (NASH)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
99 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1.4mg CS0159
Arm Type
Experimental
Arm Description
One tablet daily for 12 weeks
Arm Title
2mg CS0159
Arm Type
Experimental
Arm Description
One tablet daily for 12 weeks
Arm Title
PLACEBO
Arm Type
Placebo Comparator
Arm Description
One tablet daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
CS0159 (Linafexor)
Other Intervention Name(s)
placebo
Intervention Description
Oral QD
Primary Outcome Measure Information:
Title
MRI-PDFF
Description
To assess the changes in liver steatosis through magnetic resonance imaging (MRI) proton density fat fraction (PDFF) from baseline to Week 12
Time Frame
Week 12
Title
Adverse events
Description
To evaluate the safety and tolerability of CS0159 in patients with NASH treated over 12 weeks
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Cmax
Description
maximum concentration (Cmax) from baseline to Week 12
Time Frame
week 6, week 12
Title
tmax
Description
time to maximum plasma concentration (tmax) from baseline to Week 12
Time Frame
week 6, week 12
Title
t1/2
Description
half-life (t1/2) from baseline to Week 12
Time Frame
week 6, week 12
Title
AUC
Description
accumulation ratio of area under the concentration-time curve (AUC) in plasma from baseline to Week 12
Time Frame
week 6, week 12
Title
Pharmacodynamics (PD)
Description
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
Time Frame
week 6, week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients who meet the diagnosis of NASH.
Evidence of metabolic syndrome, except for those patients with biopsy-proven NASH.
Body mass index (BMI) >25 kg/m2, NOTE: for Asian-Americans BMI >23 kg/m2.
Stable use of other antidiabetic, weight loss, or lipid-modifying medications for at least 12 weeks prior to randomization.
Exclusion Criteria:
Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days, whichever is longer.
Previous exposure to farnesoid X receptor (FXR) agonists 3 months prior to the first dosing.
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.
Prothrombin time international normalized ratio >1.3, unless due to therapeutic anticoagulation.
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
white blood cells <3000 cells/mm3.
Alanine aminotransferase and aspartate aminotransferase (AST) >5 × ULN, or alkaline phosphatase (ALP) >1.5 × ULN.
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.
Poorly controlled hypertension (systolic >160 mm Hg, or diastolic blood pressure >100 mm Hg - mean of 3 measurements).
Uncontrolled diabetes mellitus (hemoglobin A1c >10.0% during screening).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rong Deng
Organizational Affiliation
Cascade Pharmaceuticals, Inc
Official's Role
Study Director
Facility Information:
Facility Name
National Research Institute - Gardena
City
Gardena
State/Province
California
ZIP/Postal Code
90247-3586
Country
United States
Facility Name
Velocity Clinical Research, Huntington Park
City
Huntington Park
State/Province
California
ZIP/Postal Code
90255-2959
Country
United States
Facility Name
Velocity Clinical Research - Panorama City
City
Panorama City
State/Province
California
ZIP/Postal Code
91402-3022
Country
United States
Facility Name
Velocity Clinical Research - Santa Ana
City
Santa Ana
State/Province
California
ZIP/Postal Code
92704
Country
United States
Facility Name
Ocala GI Research
City
Lady Lake
State/Province
Florida
ZIP/Postal Code
32159
Country
United States
Facility Name
Florida Research Institute
City
Lakewood
State/Province
Florida
ZIP/Postal Code
34211-4930
Country
United States
Facility Name
Floridian Clinical Research, LLC - Miami Lakes
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33016-1518
Country
United States
Facility Name
San Marcus Research Clinic, Inc - Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33014-5602
Country
United States
Facility Name
Gastroenterology Associates of Ocala
City
Ocala
State/Province
Florida
ZIP/Postal Code
34471
Country
United States
Facility Name
Oracle Clinical Research
City
College Park
State/Province
Georgia
ZIP/Postal Code
30349
Country
United States
Facility Name
Metropolitan Gastroenterology Associates - Westbank Office and Endoscopy
City
Marrero
State/Province
Louisiana
ZIP/Postal Code
70072
Country
United States
Facility Name
Raja M. Din MD, PLLC - Gastroenterology & Hepatology
City
Greenbelt
State/Province
Maryland
ZIP/Postal Code
20770-6702
Country
United States
Facility Name
Lucas Research
City
Morehead City
State/Province
North Carolina
ZIP/Postal Code
28557
Country
United States
Facility Name
Texas Liver Institute (TLI) - Austin
City
Austin
State/Province
Texas
ZIP/Postal Code
78757-7571
Country
United States
Facility Name
Pioneer Research Solutions Inc - Houston - Stancliff Rd
City
Houston
State/Province
Texas
ZIP/Postal Code
77099-4307
Country
United States
Facility Name
The Texas Liver Institute, Inc.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Clinical Trials of Texas, LLC
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of CS0159 in Subjects With NASH
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