A Phase 2a Study of Kylo-0603 Capsule in Participants With Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD)

Ki vehet részt

• Participants must meet all of the following inclusion criteria to be eligible for this study:
• Age between 18 and 70 years, inclusive
• Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) ≥ 10% at screening
• Body weight stable within 6 weeks before screening (absolute change in body weight ≤ 5%)
• Liver stiffness measurement (LSM) by FibroScan at screening: 8 kPa ≤ LSM < 15 kPa
• Body mass index (BMI) between 25.0 and 40.0 kg/m², inclusive, at screening
• Participants must have no childbearing plans during the study and for 6 months after the last dose, and must voluntarily use effective contraceptive measures
• No alcohol consumption or no history of excessive alcohol consumption. A history of excessive alcohol consumption is defined as: in the past 12 months, weekly ethanol (alcohol) intake ≥ 210 g for men and ≥ 140 g for women. Ethanol intake (g) = alcohol consumption volume (mL) × alcohol by volume (%) × 0.8
• Participants must voluntarily participate in the clinical trial, be able to sign the informed consent form (ICF), and be able to understand and comply with the trial procedures

Ki nem vehet részt

• Confirmed or suspected cirrhosis, or current or previous hepatic decompensation, including portal hypertension (e.g., esophageal varices, ascites) or hepatic encephalopathy
• Use of medications that may cause hepatic steatosis, steatohepatitis, or hepatotoxicity within 12 months before screening, including but not limited to valproic acid, tamoxifen, methotrexate, amiodarone, oral glucocorticoids > 5 mg/day prednisone or equivalent, or estrogens at doses greater than those used for contraception or hormone replacement
• Use of weight-loss medications within 6 months before screening or planned use during the study
• Current or recent use of approved metabolic dysfunction-associated steatohepatitis (MASH) therapies, or participation in another MASH clinical trial within 6 months or 5 half-lives before screening, whichever is longer
• Use of hepatoprotective drugs within 4 weeks before screening or planned use during the study
• Major surgery within 3 months before signing the informed consent form (ICF), or planned major surgery during the study
• Participation in another clinical trial of an approved or unapproved investigational drug or device within 3 months or 5 half-lives before screening, whichever is longer
• Known or suspected intolerance or allergy to the investigational drug, its excipients, or drugs with the same target
• Blood transfusion within 2 months before screening, blood donation within 1 month before screening, breastfeeding, or positive pregnancy test in female participants
• Significant systemic or major diseases other than liver disease, including recent (within 6 months before screening) congestive heart failure (New York Heart Association [NYHA] functional class III-IV), unstable coronary artery disease, arterial revascularization, respiratory disease, renal failure, stroke, transient ischemic attack, organ transplantation, psychiatric disorders, or any clinically significant disease-related event requiring hospitalization
• Chronic liver disease of other etiologies, including viral hepatitis (hepatitis B virus [HBV], hepatitis C virus [HCV]), human immunodeficiency virus (HIV), syphilis, primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, drug-induced liver disease, alcoholic liver disease, Wilson disease, or other etiologies judged by the investigator
• History of liver transplantation or planned liver transplantation
• History of thyroid disease, current use of drugs affecting thyroid function, positive thyroid-related antibodies, or abnormal thyroid function tests at screening. Thyroid-related antibodies include anti-thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb), and anti-thyroglobulin antibody (TGAb). Thyroid function tests include thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), and total thyroxine (TT4)
• History of bariatric surgery within 5 years before screening
• Poorly controlled hypertension, defined as systolic blood pressure (SBP) >= 160 mmHg or diastolic blood pressure (DBP) >= 100 mmHg based on the mean of 3 measurements at screening
• History of malignancy within 5 years before screening, or active or suspected malignancy under evaluation at screening. Adequately treated basal cell carcinoma, squamous cell skin cancer, and carcinoma in situ of the cervix are excluded
• History of drug abuse within 1 year before screening
• Diabetes other than type 2 diabetes mellitus; poor glycemic control (hemoglobin A1c [HbA1c] >= 9% or fasting plasma glucose >= 13.9 mmol/L); need for additional glucose-lowering therapy during the study; or history of severe hypoglycemia
• Receipt of insulin, glucagon-like peptide-1 (GLP-1) receptor agonists, glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, or glucagon receptor (GCGR) agonists within 6 months before screening
• Unstable doses of vitamin E, osteoporosis therapies, sodium-glucose cotransporter-2 (SGLT2) inhibitors, thiazolidinediones, statins, fibrates, or other glucose-lowering, weight-affecting, or lipid-modifying drugs within the specified period before screening
• Abnormal laboratory values at screening: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 x upper limit of normal (ULN); alkaline phosphatase (ALP) >= 2 x ULN; estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2; international normalized ratio (INR) >= 1.3; total bilirubin > 1.5 x ULN; or platelet count < lower limit of normal (LLN)
• Contraindications to magnetic resonance imaging (MRI); clinically significant electrocardiogram (ECG) abnormalities, including Fridericia's formula-corrected QT interval (QTcF) >= 450 msec in men or >= 470 msec in women at screening; or any condition that, in the investigator's opinion, may increase safety risk or interfere with study participation or compliance