Chronic Hepatitis b, Metabolic Dysfunction-associated Steatotic Liver Disease
Conditions
Keywords
Metabolic Dysfunction-associated Steatotic Liver Disease, Chronic Hepatitis b, ACT500, NM6606
Brief summary
This study is a Phase Ib, multicenter randomized, double-blind, dose-escalation, placebo-controlled trial designed to evaluate the safety, tolerability, PK, and PD profiles of multiple-dose ACT500 in participants with metabolic dysfunction-associated steatotic liver disease (MASLD) complicated with chronic hepatitis B (CHB). The trial plans to enroll 24 participants with MASLD complicated with CHB across three dose cohorts initially, each consisting of 8 participants who will receive oral ACT500 tablets once daily.
Interventions
DRUGACT500 Tablets
Once daily, orally
DRUGACT500 Placebo Tablets
Once daily, orally
Sponsors
Xiamen Amoytop Biotech Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* The participant fully understands the purpose, nature, methods of the trial, and the potential adverse reactions, voluntarily agrees to participate in this study, and signs the informed consent form. * Male or female participants aged between 18 and 60 years (inclusive) at the time of signing the informed consent form. * Liver fat content ≥10% as assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) during the screening period. * Liver stiffness measurement (LSM) by FibroScan during the screening period meets 8 kPa ≤ LSM \< 12 kPa, or liver biopsy results within 6 months prior to screening show stage F2/F3 liver fibrosis. * Hepatitis B surface antigen (HBsAg) positive for \>6 months at screening, or other evidence of chronic hepatitis B (CHB), with HBV DNA \< 20 IU/mL. * Serum alanine aminotransferase (ALT) \< 5×ULN at screening. * Received nucleos(t)ide analog (NAs) therapy for at least 1 year prior to screening and are currently on stable NA therapy (including entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, and tenofovir amibufenamide). Stable NAs therapy is defined as receiving the same treatment regimen within 3 months prior to screening. * Have at least one of the following metabolic disease risk factors: BMI ≥24.0 kg/m\^2, or waist circumference ≥90 cm (male) and ≥85 cm (female); Prediabetes: fasting blood glucose ≥6.1 mmol/L, or glycated hemoglobin (HbA1c) ≥5.7%; History of type 2 diabetes mellitus; 1.70 mmol/L ≤ fasting serum triglycerides \< 5.6 mmol/L; Fasting serum high-density lipoprotein cholesterol ≤1.0 mmol/L (male) and ≤1.3 mmol/L (female), or receiving stable-dose lipid-lowering therapy(excluding statins); Systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg, with systolic blood pressure ≤160 mmHg and diastolic blood pressure ≤100 mmHg; or receiving stable-dose antihypertensive therapy with systolic blood pressure ≤160 mmHg and diastolic blood pressure ≤100 mmHg. * Both male and female participants must agree to use adequate contraceptive methods, where: Male participants: agree to use reliable contraceptive measures from the time of signing the informed consent form until 1 months after the last dose, and have no sperm donation plans; Female participants: women of non-childbearing potential; or women of childbearing potential who are not pregnant or breastfeeding, must have a negative serum pregnancy test result at screening and within 1 day prior to the first dose, agree to use reliable contraceptive measures from the time of signing the informed consent form until 1 months after the last dose, and have no oocyte donation plans.
Exclusion criteria
* Concurrent other liver diseases, including but not limited to hepatitis C, hepatitis D, drug-induced liver disease, alcoholic liver disease, autoimmune liver disease, suspected or confirmed liver cancer, etc. * Participants with a previous or current history of other malignant tumors, liver cirrhosis (including imaging-confirmed or suspected cirrhosis, and liver biopsy-confirmed cirrhosis), or evidence of decompensated liver disease (such as ascites, esophagogastric variceal bleeding, hepatic encephalopathy), or with a history of liver transplantation. * Participants with a history or current symptoms of severe cardiovascular and cerebrovascular diseases, including but not limited to uncontrolled or severe arrhythmia (ventricular fibrillation, atrial fibrillation, etc.), myocardial infarction, coronary heart disease, uncontrolled hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg). * Participants with persistent and clinically significant medical history of respiratory, nervous, gastrointestinal, immune, hematological or psychiatric diseases, which, in the opinion of the investigator, may impose additional risks on the participant. * Participants with type 1 diabetes or poorly controlled type 2 diabetes (fasting blood glucose \>9 mmol/L within 3 months prior to screening or glycated hemoglobin \>9.5% at screening), or diabetic patients using hypoglycemic drugs other than metformin and insulin. * Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m² (calculated by the CKD-EPI formula) at screening, or with a history of severe renal impairment. * Known hemoglobinopathy, hemolytic anemia, sickle cell anemia; or hemoglobin \<115 g/L in female participants and \<130 g/L in male participants at screening; or any other conditions judged by the investigator to interfere with hemoglobin detection. * Any of the following laboratory abnormalities at screening: alkaline phosphatase (ALP) \>2 times the upper limit of normal (ULN), total bilirubin (TBIL) \>1.5 times the ULN(excluding participants with benign unconjugated hyperbilirubinemia who are deemed eligible for enrollment by the Investigator, with total bilirubin \<2×ULN and direct bilirubin \<ULN);, international normalized ratio (INR) \>1.3, albumin \<35 g/L, platelet count \<125×10⁹/L, and serum triglycerides \>5.6 mmol/L. * Participants with body weight gain or loss \>5% within 3 months prior to screening, or those receiving diet control, bariatric surgery, or using approved anti-obesity medications for weight loss indications. * Participants with a history of major trauma or surgery within 3 months prior to screening, or those scheduled to undergo surgery during the study period. * Excessive alcohol consumption for 3 consecutive months or more within 1 year prior to screening. Excessive drinking is defined as weekly ethanol intake ≥210 g for males and ≥140 g for females; or with a history of drug abuse/dependence or drug inhalation/injection within 1 year prior to screening. * Use of drugs with potential therapeutic effects on MASLD/MASH within 3 months prior to screening (e.g., GLP-1 receptor agonists, DPP4 inhibitors, SGLT2 inhibitors, FGF21 analogues, resmetirom, etc.), or drugs that may induce MASLD/MASH (e.g., amiodarone, methotrexate, tetracyclines, tamoxifen, estrogen at doses exceeding hormone replacement therapy, anabolic steroids, valproic acid, and other known hepatotoxic drugs); use of drugs that may affect the efficacy of hepatitis B treatment within 6 months prior to screening (e.g., anti-HBV drugs other than NAs, interferons, systemic immunomodulators, hepatitis B vaccines, etc.), or any other medications deemed by the investigator to interfere with the study. * Participation in other clinical drug trials within 6 months prior to screening. * Positive human immunodeficiency virus antibody (HIV-Ab) at screening; positive hepatitis C virus antibody (if positive, HCV-RNA must be below the lower limit of quantitation of the study site assay); positive hepatitis D virus antibody; or positive treponema pallidum antibody together with positive rapid plasma reagin (RPR) test (RPR shall only be performed when treponema pallidum antibody is positive). * Participants with allergic reactions to excipients of ACT500 or drugs with similar chemical structures to ACT500, or other drug allergies deemed ineligible for study participation by the investigator. * Any other conditions that render the participant unsuitable for this study as determined by the investigator, or participants who are unable to complete the trial due to personal reasons after signing the informed consent form (ICF).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse Event | Day1-112 |
| Serious Adverse Event | Day1-112 |
| body temperature | Day1,14,29,56,84,112 |
| breathe | Day1,14,29,56,84,112 |
| pulse | Day1,14,29,56,84,112 |
| blood pressure | Day1,14,29,56,84,112 |
| Number of Participants with Abnormal Laboratory Parameters Findings | Day1,14,29,56,84,112 |
| Number of participants with clinically significant change from baseline in physical examination | Day1,14,29,56,84,112 |
| PR Interval | Day14,29,56,84,112 |
| QRS Interval | Day14,29,56,84,112 |
| QT Interval | Day14,29,56,84,112 |
| QTc Interval | Day14,29,56,84,112 |
Secondary
| Measure | Time frame |
|---|---|
| Area Under Curve#0-t# | Day1,2,14,28,29 |
| Area Under the Concentration-time curve from time zero to τ at steady state | Day1,2,14,28,29 |
| Area Under Curve#0-∞# | Day1,2,14,28,29 |
| Maximum Plasma Concentration | Day1,2,14,28,29 |
| Time to Maximum (plasma) Concentration | Day1,2,14,28,29 |
| Elimination Half-Life | Day1,2,14,28,29 |
| CL/F | Day1,2,14,28,29 |
| Apparent Volume of Distribution | Day1,2,14,28,29 |
| Cmin,ss | Day1,2,14,28,29 |
| Cav,ss | Day1,2,14,28,29 |
| Rac_Cmax | Day1,2,14,28,29 |
| Rac_AUC0-tau | Day1,2,14,28,29 |
| DF | Day1,2,14,28,29 |
| MRI-PDFF-determined liver fat content (LFC) | Day29,112 |
| Fibroscan-measured liver stiffness measurement (LSM) | Day29,112 |
| AST/PLT Ratio Index | Day1,14,29,56,112 |
| Triglyceride | Day1,14,29,56,84,112 |
| Total Cholesterol | Day1,14,29,56,84,112 |
| Low-Density Lipoprotein Cholesterol | Day1,14,29,56,84,112 |
| High-Density Lipoprotein Cholesterol | Day1,14,29,56,84,112 |
| Apolipoprotein A1 | Day1,14,29,56,84,112 |
| Apolipoprotein B | Day1,14,29,56,84,112 |
| Lipoprotein(a) | Day1,14,29,56,84,112 |
| Alanine Aminotransferase | Day1,14,29,56,84,112 |
| Aspartate Aminotransferase | Day1,14,29,56,84,112 |
| Gamma-Glutamyl Transferase | Day1,14,29,56,84,112 |
| body weight | Day1,14,29,56,84,112 |
| body Mass Index | Day1,14,29,56,84,112 |
| waist circumference | Day1,14,29,56,84,112 |
| hip circumference | Day1,14,29,56,84,112 |
| Hepatitis B surface antigen | Day1,14,29,56,84,112 |
| high-sensitivity C-reactive protein | Day1,2,14,28,29 |
| Tumor necrosis factor-α | Day1,2,14,28,29 |
| Cytokeratin-18 fragment M30 | Day1,2,14,28,29 |
| Procollagen type III N-terminal peptide(Pro-C3) | Day1,2,14,28,29 |
| percent change from baseline in Pro-C3 | Day1,2,14,28,29 |
| Insulin-like Growth Factors-1 | Day1,29 |
| Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) | Day1,29 |
| percent change from baseline in IGFBP-3 | Day1,29 |
| FIB-4 | Day1,14,29,56,112 |
| Enhanced Liver Fibrosis | Day1,14,29 |
Countries
China
Contacts
CONTACTJidong Jia, Ph.D
PRINCIPAL_INVESTIGATORJidong Jia, Ph.D
Beijing Friendship Hospital
Outcome results
None listed