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

Cascade Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Nonalcoholic Steatohepatitis (NASH)

Treatments: Drug: CS0159 (Linafexor)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05591079

NASH-CS0159-002

Details and patient eligibility

About

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

Full 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.

Enrollment: 99 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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99 participants in 3 patient groups, including a placebo group

1.4mg CS0159

Experimental group

Description:

One tablet daily for 12 weeks

Treatment:

Drug: CS0159 (Linafexor)

2mg CS0159

Experimental group

Description:

One tablet daily for 12 weeks

Treatment:

Drug: CS0159 (Linafexor)

PLACEBO

Placebo Comparator group

Description:

One tablet daily for 12 weeks

Treatment:

Drug: CS0159 (Linafexor)