A Study of Chiglitazar in Patients With Metabolic Dysfunction-associated Steatohepatitis and Type 2 Diabetes Mellitus (CHIG-MASH)

Chiglitazar in Combination With Anti-Inflammatory and Hepatoprotective Therapy for the Treatment in MASH Associated With T2DM: a Prospective, Multicentre, Randomised, Double-blind, Placebo-controlled Study

This trial aims to evaluate the efficacy and safety of chiglitazar as a combination therapy for patients with MASH and T2DM.

Study Overview

• Status: Recruiting
• Conditions: T2DM (Type 2 Diabetes Mellitus); MASH - Metabolic Dysfunction-Associated Steatohepatitis
• Intervention / Treatment: Drug: Chiglitazar Placebo; Drug: vitamin E; Drug: Polyene Phosphatidyl choline; Drug: Chiglitazar

Detailed Description

Metabolic dysfunction-associated steatohepatitis (MASH), used to be called non-alcoholic steatohepatitis (NASH), is a manifestation of the metabolic syndrome in the liver, particularly when co-occurring with type 2 diabetes (T2DM), presents a significant therapeutic challenge due to a higher risk of fibrosis progression and adverse outcomes. While new treatments for MASH are emerging, their efficacy in the T2DM subpopulation remains an area of unmet need. Chiglitazar is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist that regulates key pathways in lipid metabolism, glucose homeostasis, and inflammation. This trial aims to evaluate the efficacy and safety of chiglitazar as a combination therapy for patients with MASH and T2DM.

This is a prospective, multicentre, randomised, double-blind, placebo-controlled study. The trial will enroll 300 adult patients aged 18-75 years with biopsy-confirmed MASH and fibrosis stage F1b or higher. Participants will be randomised (1:1) to receive either chiglitazar 48 mg daily or a matching placebo. All participants will also receive background therapy consisting of vitamin E (100 mg three times a day) and polyene phosphatidylcholine (456 mg three times a day). The treatment duration is 72 weeks. The primary efficacy endpoint is the resolution of steatohepatitis with no worsening of liver fibrosis. Key secondary endpoints include improvement in liver fibrosis by at least one stage and changes in metabolic and liver safety biomarkers.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hai Li, professor; Phone Number: +86 13818525494; Email: haili_17@126.com
• Study Contact Backup: Name: Lianyong Liu, professor; Phone Number: +86 13564144866; Email: chinallu@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100015
      • Not yet recruiting
      • Ditan Hospital of integrated traditional Chinese and Western Medicine Center
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400038
      • Not yet recruiting
      • Southwest Hospital of Third Military Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350005
      • Not yet recruiting
      • The First Affiliated Hospital of Fujian Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Not yet recruiting
      • The Third Affiliated Hospital of Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510515
      • Not yet recruiting
      • Southern Hospital
  • Hebei
    • Wuhan, Hebei, China, 430022
      • Not yet recruiting
      • Wuhan Union Hospital of Huazhong University of Science and Technology
  • Hubei
    • Shiyan, Hubei, China, 442000
      • Not yet recruiting
      • Taihe Hospital
  • Hunan
    • Changsha, Hunan, China, 410008
      • Not yet recruiting
      • Xiangya Hospital of Central South University
  • Jilin
    • Changchun, Jilin, China, 130021
      • Not yet recruiting
      • The first Affiliated Hospital of Jilin University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200001
      • Not yet recruiting
      • Renji hospital of Shanghai Jiao Tong University School of Medical
    • Shanghai, Shanghai Municipality, China, 200020
      • Not yet recruiting
      • Ruijin Hospital of Shanghai Jiaotong University School of Medicine
    • Shanghai, Shanghai Municipality, China, 200083
      • Not yet recruiting
      • Shanghai Public Health Clinical Center
    • Shanghai, Shanghai Municipality, China, 200125
      • Recruiting
      • Shanghai Punan Hospital of Pudong New District (Punan Branch of Renji Hospital, Shanghai Jiaotong University School of Medicine)
  • Shanxi
    • Xi’an, Shanxi, China, 710061
      • Not yet recruiting
      • The First Affiliated Hospital of Xi'an Jiao Tong University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300192
      • Not yet recruiting
      • Tianjin Second People's Hospital
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830054
      • Not yet recruiting
      • The First Teaching Hospital of Xinjiang Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Not yet recruiting
      • The First Affiliated Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Men and women aged at least 18 years and under 75 years (inclusive) at the time of obtaining consent.
2. Participants must be diagnosed as T2DM and HbA1c ≤ 9.5% at time of screening.
3. Participants must take Fibroscan examination with the result of CAP ≥ 238 dB/m and LSM>8.5 kPa.
4. Diagnosis of MASH by liver biopsy, with NAFLD Activity Score (NAS) ≥4 with ≥1 point for each component, and fibrosis stage 1b or more over according to the NASH Clinical Research Network (CRN) scoring system. (or liver biopsy not more than 6 months prior to screening)
5. Stable body weight (≤10% body weight change) for at least 3 months.
6. Possess good understanding and behavior and be able to take the medication daily as required by the trial.
7. Willing to sign the informed consent.

Exclusion Criteria:

1. Alcohol consumption >20g ethyl alcohol/day for women and >40g ethyl alcohol/day for men.

2. Evidence of other forms of chronic liver disease:

   1. Alcoholic liver disease,
   2. Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg) or hepatitis B DNA,
   3. Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA or positive hepatitis C antibody (anti-HCV),
   4. Evidence of autoimmune liver disease as defined by compatible liver histology,
   5. Current drug-induced liver disease as defined on the basis of typical exposure and history,
   6. Suspected or proven liver cancer,
   7. Any other type of liver disease other than MASH.
3. Uncontrolled T2DM defined as HbA1c >9.5% at time of screening or Type 1 diabetes mellitus (T1DM).
4. Patients with T2DM who have a history of diabetic ketoacidosis, proliferative diabetic retinopathy, diabetic maculopathy or severe non-proliferative diabetic retinopathy that requires acute treatment.

5. Any of the following cardiovascular conditions within 6 months prior to screening:

   1. acute myocardial infarction (MI),
   2. cerebrovascular accident (stroke),
   3. unstable angina,
   4. hospitalization due to congestive heart failure (CHF)
   5. New York Heart Association Functional Classification IV CHF
6. History of an active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.
7. Uncontrolled hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg).
8. Renal impairment measured as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2.
9. Known clinically significant gastric emptying abnormality (for example, severe diabetic gastroparesis or gastric outlet obstruction) or chronically take drugs that directly affect gastrointestinal motility.
10. Have a known self or family history (first-degree relative) of multiple endocrine neoplasia type 2A or type 2B, thyroid C-cell hyperplasia, or medullary thyroid carcinoma (MTC).
11. Evidence of untreated hypothyroidism or hyperthyroidism based on clinical or laboratory evaluation.
12. A transplanted organ (corneal transplants allowed) or awaiting an organ transplant.
13. Women of childbearing potential: positive pregnancy test during screening or at randomization or unwillingness to use an effective form of birth control during the trial (at least include one barrier contraceptive method) and breast feeding.
14. Use of drugs associated with hepatic steatosis (e.g., amiodarone, methotrexate, tamoxifen) for more than 2 weeks in the 3 months prior to screening.
15. Current use of medication is associated with weight gain, except when on stable dose for at least 3 months prior to screening and remaining on stable dose during the study.
16. Receiving or having received (within 3 months of screening) chronic (>2 weeks) systemic glucocorticoid therapy.
17. Use of treatment targeting MASH for more than 2 weeks in the 3 months prior to screening (GLP-1 receptor agonists or PPAR pan agonists).
18. Any other condition which in the opinion of investigator would impede compliance or hinder completion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Chiglitazar Placebo + vitamin E + polyene phosphatidyl choline; Chiglitazar placebo given orally once a day	Drug: Chiglitazar Placebo; Chiglitazar Placebo 48mg/day; Other Names: simulant of chiglitazar; Drug: vitamin E; Vitamin E 100mg/three times a day; Other Names: Laiyi; Drug: Polyene Phosphatidyl choline; Polyene Phosphatidyl choline 456mg/three times a day; Other Names: Yi Shan Fu
Experimental: 48mg Chiglitazar + vitamin E + polyene phosphatidyl choline; 48mg Chiglitazar given orally once a day	Drug: vitamin E; Vitamin E 100mg/three times a day; Other Names: Laiyi; Drug: Polyene Phosphatidyl choline; Polyene Phosphatidyl choline 456mg/three times a day; Other Names: Yi Shan Fu; Drug: Chiglitazar; Chiglitazar 48mg/day; Other Names: Carfloglitazar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with resolution of steatohepatitis and no worsening of liver fibrosis	The definition of resolution of steatohepatitis was based on the following criteria: ballooning=0, inflammation=0,1 and any level of steatosis in NAS	week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with an improvement in liver fibrosis by ≥ 1 stage (NASH CRN fibrosis score) and no worsening of steatohepatitis	Evaluation of fibrosis stage was based on the nonalcoholic steatohepatitis clinical research network (NASH CRN) fibrosis staging system, participants were evaluated with the NASH CRN scoring system with ≥1-point reduction without worsening of MASH (defined as no increase in the NAS score).	week 72
Percentage of participants with resolution of steatohepatitis and improvement in liver fibrosis	Participants were evaluated with the NASH CRN scoring system with ≥1-point reduction and with resolution of steatohepatitis	week 72
Change in body mass index from baseline	The body mass index = weight (kg) / height (m)².	Week 4, 8, 12, 24, 36, 48, 60, 72
Changes in liver stiffness values assessed by transient elastography from baseline	Measured by Fibroscan, to evlaute the severity of liver fibrosis	Week 4, 8, 12, 24, 36, 48, 60, 72
Change in CAP values assessed by transient elastography from baseline	Measured by Fibroscan, to evlaute the severity of liver fat	Week 4, 8, 12, 24, 36, 48, 60, 72
Change in HbA1c from baseline	Central lab test	Week 4, 8, 12, 24, 36, 48, 60, 72
Changes in blood fasting plasma glucose level from baseline	Central lab test	Week 4, 8, 12, 24, 36, 48, 60, 72
Changes of blood lipids level from baseline	Includeing TC, LDL-C, HDL-C, VLDL-C, non-HDL-C, TG	Week 4, 8, 12, 24, 36, 48, 60, 72
Changes of liver function from baseline	Includeing AST, ALT, GGT, AKP	Week 4, 8, 12, 24, 36, 48, 60, 72
Changes of MRI-PDFF from baseline	magnetic resonance imaging-proton density fat fraction	Week 4, 8, 12, 24, 36, 48, 60, 72

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Collaborators: Chipscreen Biosciences, Ltd.
• Investigators: Principal Investigator: Hai Li, professor, Shanghai Punan Hospital of Pudong New District (Punan Branch of Renji Hospital, Shanghai Jiaotong University School of Medicine)

Publications and helpful links

General Publications

• He K, Chen F, Shao R, Jiang W, Gu W, Huang Z, Gan Y, Wang Y, Wu H, Zhao Y, Zhang B, Gao L, Yan X, Yao C, Shen C, Ji P, Wei J, Bian Y, Lu Y, Abuduaini A, Liu L, Li H. Chiglitazar in combination with anti-inflammatory and hepatoprotective therapy for the treatment of MASH associated with T2DM: a prospective, multicentre, randomised, double-blind, placebo-controlled study protocol. BMJ Open. 2026 May 18;16(5):e116945. doi: 10.1136/bmjopen-2026-116945.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 11, 2025
• First Submitted That Met QC Criteria: December 23, 2025
• First Posted (Actual): December 26, 2025

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: type 2 diabetes; liver biopsy; metabolic dysfunction-associated steatohepatitis; chiglitazar
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrans; Benzopyrans; Vitamin E; chiglitazar
• Other Study ID Numbers: KS2540

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