A Phase 2, Multicenter, Placebo-Controlled, Randomized, Double-Blind, 48-Week Study to Evaluate the Efficacy and Safety of Combination Therapy of K-877-ER and CSG452 in Patients with Noncirrhotic Nonalcoholic Steatohepatitis (NASH) with Liver Fibrosis

Phase 1

Conditions: oncirrhotic Nonalcoholic Steatohepatitis (NASH) with Liver Fibrosis
MedDRA version: 24.1Level: LLTClassification code 10086370Term: NASH with fibrosisSystem Organ Class: 100000004871
Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

Registration Number: EUCTR2021-003901-23-ES

Lead Sponsor: Kowa Research Institute, Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 400

Inclusion Criteria

Criteria for Inclusion:
Patients are eligible for the study if all of the following criteria are met:
1.Able to understand and comply with study procedures and give written informed consent
2.Age > or = 18 years
3.NAS > or = 4 with a score of at least 1 in each component of the NAS (steatosis, lobular inflammation, and ballooning) at Visit 2 liver biopsy, or a historical liver biopsy performed within 12 weeks of randomization
4.Fibrosis stage of 1 or greater and below 4 on NASH CRN fibrosis staging system at Visit 2 liver biopsy, or a historical liver biopsy performed within 12 weeks of randomization
5.Patient can be with or without T2DM, but T2DM patients must be well controlled on a stable dose of antidiabetic medication for at least 3 months prior to randomization. Patients without T2DM must have fasting plasma glucose > or = 100 mg/dL at Visit 1
6.Patients must not be breastfeeding and must have a negative serum pregnancy test at Visit 1. Female patients of childbearing potential must use one of the following acceptable birth control methods as specified before enrollment and throughout the study:
a.Surgical sterilization (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) at least 6 months before the first dose of study drug
b.Intrauterine device in place for at least 3 months before the first dose of study drug and throughout the study
c.Barrier method (condom or diaphragm) with spermicide for at least 30 days before the first dose of study drug and throughout the study
d.Surgical sterilization of the male partner (vasectomy at least 6 months before the first dose of study drug)
e.Hormonal contraceptives with a barrier method for at least 3 months before the first dose of study drug and throughout the study
Female patients are not considered to be of childbearing potential if they meet at least one of the following two criteria as documented by the Investigator:
-They have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at minimum 1 menstrual cycle prior to signing the Informed Consent Form
-They are postmenopausal, defined as 1 year since the last menstrual period for women > or = 55 years of age and have a follicle-stimulating hormone (FSH) level in menopausal range (defined as > or =20 miU/mL and <122 miU/mL) for women <55 years of age
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 400
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-Participation in another clinical trial involving an investigational agent within 30 days prior to signing the Informed Consent Form for this study.
-Ongoing or recent consumption of significant amounts of alcohol. Significant alcohol consumption is defined as >21 standard drinks per week in men and >14 standard drinks per week in women over a 2-year period prior to randomization. A standard alcoholic drink is any drink that contains about 14 g of pure alcohol.-Evidence of other forms of chronic liver disease -Patients listed for liver transplantation, or a history of liver transplantation -Initiation of, or change in, current doses of thiazolidinediones, agents with GLP-1 receptor agonist activity, or vitamin E within 6 months of randomization -Current or planned use of fibrates, agents with potent selective peroxisome proliferator-activated receptor alpha (PPARalpha) agonist activity, or sodium glucose co transporter 2 (SGLT2) inhibitors within 6 months of randomization -Patients with type 1 diabetes mellitus -Patients with poorly controlled T2DM as defined by HbA1c >10% at Visit 1 -Patients with severe ketosis, diabetic coma, or pre-coma -Initiation of, or change in, current TG-lowering therapy within 3 months of randomization -TG-lowering therapy is defined as niacin >100 mg/day or dietary supplements or prescription of omega-3 fatty acids 1000 mg/day. -Initiation of, or change in, current doses of orlistat, lorcaserin, phentermine, topiramate, naltrexone, or bupropion or any other medication that could promote weight loss in the opinion of the investigator within 3 months of randomization -Patients with severe infections, during a perioperative period, or with serious injuries -Patients with urinary tract infection or genital infection -History of symptomatic gallstone disease -Patients with severe renal impairment at Visit 1, who are receiving dialysis at Visit 1, or who have had a kidney transplant, regardless of level of renal function -Patients with weight change of 5% or more within 3 months of randomization -Patients who performed significant attempt to change diet and exercise, at the investigator’s opinion, within 6 months of screening -Model for End-stage Liver Disease (MELD) score >12 at Visit 1 -Presence of clinical or histological evidence of compensated cirrhosis, or biochemical evidence of compensated cirrhosis -Inability to safely obtain a liver biopsy -Inability to safely obtain a MRI -History or evidence of major and clinically significant, cardiovascular, pulmonary, renal, hematologic, gastrointestinal endocrine, immunologic, dermatologic, neurologic, psychiatric, oncologic, or allergic disease that would interfere with the conduct of the study or interpretation of the data
-History of malignancy within the past 5 years, except for basal or squamous cell skin carcinoma that has undergone curative therapy -Any past history of hepatocellular carcinoma (HCC) and/or HCC treatment -History of bariatric surgery within 5 years of Screening -Uncontrolled hypertension at Visit 1 (systolic blood pressure 160 mm Hg and/or diastolic blood pressure 100 mm Hg after 5 minutes of sitting) Patients with evidence of portal hypertension -Known infection with human immunodeficiency virus (HIV) 1 or HIV 2 -Known hypersensitivity or intolerance to fibrates, PPARalfa agonists or SGLT2 inhibitors -Anticipation of major surgery during the study -Current or anticipated chronic use of cyclosporine, rifampicin, or other inhibitors of OA

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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