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

Korábbi kezelés

• 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.

Más betegség

• 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.

Laborértékek

• 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.

• 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.