A Study Comparing IBI362 vs Semaglutide in Chinese Overweight or Obese Adults With Metabolic Dysfunction-associated Fatty Liver Disease （MAFLD）

A Multicenter, Randomized, Open-label Phase III Study to Compare the Efficacy and Safety of IBI362 and Semaglutide in Chinese Overweight or Obese Subjects With Metabolic Dysfunction-associated Fatty Liver Disease (GLORY-3)

This is a multicenter, randomized, open-label Phase 3 clinical study comparing the efficacy and safety of IBI362 9 mg QW versus Semaglutide 2.4 mg QW in overweight or obese (BMI≥27kg/m2) MAFLD subjects. Subjects will be randomly assigned to IBI362 9 mg and Semaglutide 2.4 mg groups. All study treatment will be administered once-weekly and subcutaneously. The entire trial cycle includes a 4-week screening period, a 48-week open-label treatment period, and a 12-week drug withdrawal safety follow-up period.

Study Overview

• Status: Active, not recruiting
• Conditions: Overweight; Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD)
• Intervention / Treatment: Drug: semaglutide; Drug: IBI362

• Study Type: Interventional
• Enrollment (Actual): 479
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Beijing Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female, age 18 years or older at the time of signing informed consent
2. diagnosed as MAFLD according to the Chinese Guideline for the prevention and treatment of metabolic dysfunction-associated (non-alcoholic) fatty liver disease (Version 2024)
3. liver fat content ≥8% measured by MRI-PDFF
4. BMI≥27 kg/m2
5. Weight change ≤5% within 3 months before screening
6. HbA1c≤10%

Exclusion Criteria:

1. Subjects who the investigator thinks may be allergic to the components in the study drug or similar drugs
2. Used drugs or alternative therapies with weight loss effects within 3 months before screening, including but not limited to: GLP-1 receptor agonists, orlistat, phenylpropanolamine, chlorpheniramine, phentermine etc.
3. Received chronic (>2 weeks) systemic glucocorticoid treatment within 3 months before screening (excluding topical, intraocular, intranasal, and inhaled administration)
4. Previous diagnosis of type 1 diabetes (including adult latent autoimmune diabetes)
5. Active or untreated malignant tumors within 5 years before screening, or patients are in remission of clinical malignant tumors (except patients with skin basal cell carcinoma and squamous cell carcinoma, cervical carcinoma in situ, prostate carcinoma in situ or papillary thyroid carcinoma who have no recurrence after surgery)
6. Mental illness existed in the past or at the time of screening, and the researcher thinks it is not suitable to participate in this study
7. Pregnant or lactating women, or men or women who are fertile and unwilling to use contraception throughout the study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Semaglutide	Drug: semaglutide; Once-weekly injections of gradually increased doses, subcutaneously (SC): starting dose is 0.25 mg, after 4 weeks of administration, increase to 0.5 mg; After another 4 weeks, increase to 1mg; After another 4 weeks, increase to 1.7mg; After another 4 weeks, increase to the maximum 2.5mg for 32 weeks
Experimental: IBI362	Drug: IBI362; Once-weekly injections of gradually increased doses of IBI362, subcutaneously (SC): starting dose is 2.0 mg, after 4 weeks of administration, increase to 4.0 mg; After another 4 weeks, increase to 6mg; After another 4 weeks, increase to the maximum dose 9mg for 36 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
percentage change in body weight from baseline	at Week 48
percentage change in liver fat content from baseline measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)	at Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage change in liver fat content from baseline measured by MRI-PDFF		at Week 8, 16, and 24
Absolute value change in liver fat content from baseline measured by MRI-PDFF		at Week 8, 16, 24, and 48
Proportion of subjects with weight loss >10% from baseline and liver fat content <5%		at week 48
percentage change in body weight from baseline		at week 24
Changes in systolic blood pressure and diastolic blood pressure from baseline		at week 48
percentage changes in total cholesterol,triglyceride (TG), non-High Density Lipoprotein Cholesterol (non-HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), HDL-C (High Density Lipoprotein Cholesterol) from baseline		at week 48
Changes in serum uric acid from baseline		at week 48
Changes in hemoglobin A1c (HbA1c) from baseline		at week 48
Changes in Homeostasis Model Assessment 2-B (HOMA2-B) from baseline		at week 48
Changes in Homeostasis Model Assessment 2-IR (HOMA2-IR) from baseline		at week 48
Changes of scores in 36-item Short-Form Health Survey version 2(SF-36v2) questionnaire from baseline	Using norm-based scoring (NBS)，each subscale has a different maximum and minimum score, with higher scores reflecting better levels of functioning	at week 48
Changes of scores in The Impact of Weight on Quality of Life-Lite Clinical Trials Version(IWQoL-Lite-CT) questionnaire from baseline	Total score ranging from 0 to 100, with higher scores reflecting better levels of functioning	at week 48

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
• Investigators: Principal Investigator: Lixin Guo, M.D, Beijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: March 11, 2025
• First Submitted That Met QC Criteria: March 17, 2025
• First Posted (Actual): March 19, 2025

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; semaglutide; mazdutide
• Other Study ID Numbers: CIBI362B303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No