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: 10019805 - Hepatobiliary disorders; Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

• Registration Number: EUCTR2021-003901-23-BG
• Lead Sponsor: Kowa Research Institute, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-02-22
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

Criteria for Inclusion:
Subjects 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 =18 years
3.NAS =4 with a score of at least 1 in each component of the NAS (steatosis, lobular inflammation, and ballooning) at the baseline 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 the baseline biopsy, or a historical liver biopsy performed within 12 weeks of randomization
5.Subject can be with or without T2DM, but T2DM subjects must be well controlled on a stable dose of antidiabetic medication for at least 3 months prior to randomization. Subjects without T2DM must have fasting plasma glucose = 100 mg/dL at Visit 1
6.Female Subjects must not be breastfeeding and must have a negative serum pregnancy test at Visit 1 if they are women of childbearing potential. Female subjects 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 subjects 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 without an alternative medical cause or have a follicle-stimulating hormone (FSH) level in menopausal range (defined as >20 miU/mL and <122 miU/mL) in women who are not using hormonal contraception or hormonal replacement therapy and are =50 years of age.
- For women =50 years old, =2 years since her last menstrual period without an alternative medical cause, and documented FSH level in the postmenopausal range
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 300
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, or Alcohol Use Disorders Identification Test - Concise (AUDIT-C) score =3 in females or =4 in males during the Screening Period. 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 -Subjects 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 (PPARa) agonist activity, or sodium glucose co transporter 2 (SGLT2) inhibitors within 6 months of randomization -Subjects with type 1 diabetes mellitus -Subjects with poorly controlled T2DM as defined by HbA1c >10% at Visit 1 -Subjects with a prior history of venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), or a confirmed diagnosis of a hypercoagulable state -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 -Subjects with severe infections, during a perioperative period, or with serious injuries -Subjects with urinary tract infection or genital infection -History of symptomatic gallstone disease -Subjects 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 -Subjects with weight change of 5% or more between Visit 2 and randomization -Subjects 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 an MRI (US sites) -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) Subjects with evidence of portal hypertension -Known infection with human immuno

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified