A Study of UBT251 in Participants With Metabolic Dysfunction-Associated Steatohepatitis (MASH)

NCT07145151 | Recruiting Phase 2

• 2 other identifiers: TUL-UBT251（Ⅱ-3）202501Approved No.:2023LP01795
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled Phase 2 clinical study evaluating the efficacy and safety of UBT251 in MASH subjects. Subjects will be randomly assigned to UBT251 2mg-dose, 4mg-dose，6mg-dose and placebo groups. The entire trial cycle includes a 6-week screening period, a 48-week double-blind treatment period, and a 4-week follow-up period.

Conditions

Metabolic Dysfunction-associated Steatohepatitis (MASH)

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With MASH resolution With no Worsening of Fibrosis on Liver Histology

  Baseline, Week 48

Secondary Outcomes (25)

• Proportion of Participants with MASH improvement with a ≥1-stage histological improvement in liver fibrosis.

  Baseline, Week 48

• Proportion of Participants with MASH resolution with a ≥1-stage histological improvement in liver fibrosis.

  Baseline, Week 48

• Percentage of Participants With ≥1 Point Decrease in Fibrosis Stage With No Worsening of MASH on Liver Histology

  Baseline, Week 48

• Mean Absolute Change and Percent Change from Baseline in Body Weight [kg]

  Baseline, Week 12, Week 24, Week 48

• Changes from baseline in waist circumference[cm]

  Baseline, Week 12, Week 24, Week 48

Study Arms (4)

UBT251 Low Dose

EXPERIMENTAL

Dose level 1,SC, once a week for 4 weeks; Dose level 2,SC, once a week for 4 weeks; Dose level 3,SC,once a week for 4 weeks; Dose level 3,SC, once a week for 36 weeks.

Drug: UBT251

Placebo

PLACEBO COMPARATOR

Placebo administered subcutaneously (SC) once a week for 48 weeks.

Drug: Placebo

UBT251 Middle Dose

EXPERIMENTAL

Dose level 2,SC, once a week for 4 weeks; Dose level 3,SC, once a week for 4 weeks; Dose level 4,SC,once a week for 4 weeks; Dose level 4,SC, once a week for 36 weeks.

Drug: UBT251

UBT251 High Dose

EXPERIMENTAL

Dose level 2,SC, once a week for 4 weeks; Dose level 3,SC, once a week for 4 weeks; Dose level 4,SC,once a week for 4 weeks; Dose level 5,SC, once a week for 36 weeks.

Drug: UBT251

Interventions

UBT251 DRUG

UBT251 administered subcutaneously (SC) once a week.

UBT251 High Dose; UBT251 Low Dose; UBT251 Middle Dose

Placebo DRUG

Placebo,SC,once a week for 48 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years (inclusive) at screening; sex unrestricted.
• Subjects with centrally confirmed MASH (metabolic dysfunction-associated steatohepatitis) based on liver histopathology must meet all the following criteria:
• NAS (Appendix 1) ≥ 4 （with at least 1 point each for lobular inflammation and ballooning degeneration）;
• CRN fibrosis stage (see Appendix 2) of F2 or F3 (a liver biopsy obtained ≤ 6 months before screening is acceptable if it meets the above criteria).
• Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) ≥ 8 % at screening (MRI-PDFF results obtained within 2 months prior to screening at the trial site are acceptable).
• Subjects must have \<5% body weight fluctuation during the 6 weeks prior to randomization (based on self-reported data), calculated as: \[(Highest weight - Lowest weight) / Highest weight\] × 100%. For subjects using historical liver biopsy, documented weight change from biopsy to randomization must also be \< 5 %.
• At least one cardiometabolic risk factor at screening:
• Body mass index (BMI) ≥ 24.0 kg/m², or waist circumference ≥90 cm for males or ≥85 cm for females;
• Blood pressure ≥ 130/85 mmHg, or on antihypertensive therapy;
• Fasting triglycerides ≥ 1.70 mmol/L and \< 5.6 mmol/L, or on lipid-lowering therapy;
• Fasting HDL-C ≤ 1.0 mmol/L for males or ≤ 1.3 mmol/L for females; or on lipid-lowering therapy;
• Fasting glucose ≥ 6.1 mmol/L or glycated hemoglobin (HbA1c) ≥ 5.7 %, or documented history of type 2 diabetes mellitus (T2DM), or Homeostatic Model Assessment of Insulin Resistance index ≥ 2.5.
• Subjects with type 2 diabetes mellitus (T2DM) must meet glycated hemoglobin (HbA1c) ≤ 9.0 % at screening (local result obtained ≤ 2 weeks before randomization accepted), and stable glycemic control regimen for at least 3 months prior to screening: subjects must be on diet and exercise control alone, or in combination with stable-dose glucose-lowering medications, with the following requirements::
• Diet and exercise alone;
• Stable-dose use of metformin, sulfonylureas, sodium-glucose cotransporter-2 (SGLT2) inhibitors, or insulin, stable insulin dose defined as ≤35% variation in total daily insulin dose; 7. Subjects (including partners) must have no pregnancy plans from screening through 6 months post-trial and must practice contraception during the study, with no plans to donate sperm/oocytes for 6 months after trial completion.

You may not qualify if:

• Known hypersensitivity to the investigational product or any of its excipients, or allergy to other GLP-1 receptor agonists, or clinically significant history of multiple/severe drug allergies, or current allergic diseases or hypersensitivity diathesis;
• Previous use of any of the following drugs or treatments:
• \) Use of GLP-1 receptor agonists (GLP-1R), or GLP-1R/GCGR agonists, or GLP-1R/GIPR/GCGR agonists within 3 months prior to screening; 2) Cumulative use for ≥4 weeks within 3 months prior to screening, use within 1 month prior to screening, or planned use during the trial of vitamin E (dose \>400 IU/day), thiazolidinediones, polyunsaturated fatty acids, or ursodeoxycholic acid; 3) Cumulative use for ≥4 weeks within 3 months prior to screening, use within 1 month prior to screening, or planned use during the trial of drugs associated with liver injury, hepatic steatosis, or steatohepatitis: including amiodarone, methotrexate, systemic glucocorticoids (dose \>5 mg/day prednisone equivalent), estrogens (dose exceeding hormone replacement therapy or contraceptive use), tetracyclines, tamoxifen, anabolic steroids, valproate, or restricted drugs, or any drug deemed likely to interfere with efficacy or safety evaluations; 4) Unstable doses of statins, fibrates, or PCSK9 inhibitors within 1 month prior to screening; 3.History or evidence of any of the following diseases:
• Chronic liver disease other than MASH (e.g., autoimmune liver disease, primary biliary cholangitis, primary sclerosing cholangitis, chronic liver disease-related ascites, esophageal varices, hepatic encephalopathy, etc.).
• Diagnosis of type 1 diabetes or other specific types of diabetes, except resolved gestational diabetes;
• Acute pancreatitis or chronic pancreatitis within 1 year prior to screening, history of pancreatic surgery; or symptomatic gallbladder disease within 1 year prior to screening (e.g., choledocholithiasis, multiple gallstones, etc., except those who underwent cholecystectomy or stone removal);
• Personal or family history (first-degree relatives-parents, children, or siblings) of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2);
• History of severe psychiatric disorders, including but not limited to depression, suicidal tendencies or attempts, schizophrenia, bipolar disorder, etc.;
• Clinically significant active cardiovascular/cerebrovascular disease within 6 months prior to screening, defined as: ① Myocardial infarction (MI) or unstable angina; ② Cardiac-related surgery (including coronary artery bypass grafting, percutaneous coronary intervention); ③Congestive heart failure (New York Heart Association \[NYHA\] Class III-IV) (see Appendix 3); ④ Cerebrovascular accident (except old lacunar infarction), including but not limited to stroke/transient ischemic attack; ⑤ Other cardiovascular or cerebrovascular diseases deemed unsuitable for trial participation by the investigator;
• Retinal diseases requiring urgent treatment at screening (including but not limited to retinal vascular disorders, retinal inflammation, retinal detachment, retinal degeneration, etc.), as assessed by the investigator;
• History of severe hypoglycemic coma or frequent hypoglycemia (≥1 episode/week) within 2 months prior to enrollment (defined as fingertip or venous blood glucose \<3.9 mmol/L for T2DM subjects or \<2.8 mmol/L for non-T2DM subjects);
• Gastroparesis or other gastrointestinal motility disorders (e.g., pyloric obstruction, intestinal obstruction, etc.), uncontrolled gastroesophageal reflux disease, or gastrointestinal conditions deemed by the investigator to increase drug-related risks (e.g., severe active ulcers, inflammatory bowel disease, acute gastroenteritis, symptomatic chronic gastritis, functional gastrointestinal disorders, intestinal tuberculosis, etc.);
• Major surgery, severe trauma, or severe infection within 1 month prior to screening, deemed unsuitable for participation by the investigator;
• History of malignancy (except adequately treated cervical carcinoma in situ, basal or squamous cell skin cancer, localized prostate cancer post-radical therapy, ductal carcinoma in situ of the breast post-radical therapy, and papillary thyroid carcinoma post-radical therapy);
• Concurrent diseases deemed by the investigator to affect subject safety, efficacy evaluation, or compliance, e.g., neurological, endocrine, psychiatric, etc. ; 4.Laboratory abnormalities at screening meeting any of the following criteria:

Sponsors & Collaborators

• The United Bio-Technology (Hengqin) Co., Ltd.: lead

Study Sites (1)

Beijing Tsinghua ChangGung Hospital

Beijing, Beijing Municipality, 100044, China

RECRUITING

Central Study Contacts

Haiyan Zhang

CONTACT

+86 189 9816 5570; zhanghy@tul.com.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2025
• First Posted: August 28, 2025
• Study Start: September 30, 2025
• Primary Completion (Estimated): June 4, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: November 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)