This trial aims to evaluate the efficacy and safety of chiglitazar as a combination therapy for patients with MASH and T2DM.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
300
Chiglitazar Placebo 48mg/day
Chiglitazar 48mg/day
Vitamin E 100mg/three times a day
Ditan Hospital of integrated traditional Chinese and Western Medicine Center
Beijing, Beijing Municipality, China
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
Time frame: week 72
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).
Time frame: 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
Time frame: week 72
Change in body mass index from baseline
The body mass index = weight (kg) / height (m)².
Time frame: 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
Time frame: 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
Time frame: Week 4, 8, 12, 24, 36, 48, 60, 72
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Polyene Phosphatidyl choline 456mg/three times a day
Southwest Hospital of Third Military Medical University
Chongqing, Chongqing Municipality, China
NOT_YET_RECRUITINGThe First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, China
NOT_YET_RECRUITINGThe Third Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, China
NOT_YET_RECRUITINGSouthern Hospital
Guangzhou, Guangdong, China
NOT_YET_RECRUITINGWuhan Union Hospital of Huazhong University of Science and Technology
Wuhan, Hebei, China
NOT_YET_RECRUITINGTaihe Hospital
Shiyan, Hubei, China
NOT_YET_RECRUITINGXiangya hospital of Central South University
Changsha, Hunan, China
NOT_YET_RECRUITINGThe First Affiliated Hospital of Jilin University
Changchun, Jilin, China
NOT_YET_RECRUITINGRenji hospital of Shanghai Jiao Tong University School of Medical
Shanghai, Shanghai Municipality, China
NOT_YET_RECRUITING...and 7 more locations
Change in HbA1c from baseline
Central lab test
Time frame: Week 4, 8, 12, 24, 36, 48, 60, 72
Changes in blood fasting plasma glucose level from baseline
Central lab test
Time frame: 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
Time frame: Week 4, 8, 12, 24, 36, 48, 60, 72
Changes of liver function from baseline
Includeing AST, ALT, GGT, AKP
Time frame: Week 4, 8, 12, 24, 36, 48, 60, 72
Changes of MRI-PDFF from baseline
magnetic resonance imaging-proton density fat fraction
Time frame: Week 4, 8, 12, 24, 36, 48, 60, 72