The Efficacy and Safety of Chiglitazar in Patients with MAFLD-related Cirrhosis

NCT06773221 | Not Yet Recruiting

• 1 other identifier: 2024-P2-487-01
• Study Type: interventional
• Target: 195
• Locations: 1 country
• Sites: 4

Brief Summary

A total of 195 adult patients with biopsy-proven or clinically diagnosed metabolic dysfunction-associated with fatty liver disease(MAFLD)-related cirrhosis will be randomly divided into two arms. One arm will receive Chiglitazar(64 mg) treatment, while the other arm will receive placebo treatment, lasting for 72 weeks. Both the researchers and the participants will be blinded. The primary outcome is the reversal rate of cirrhosis assessed by magnetic resonance elastography. Secondary outcomes include outcome events, changes in histopathological fibrosis stage, non-invasive fibrosis tests, glucose and lipid metabolism indicators.

Conditions

Metabolic Dysfunction Associated Fatty Liver Disease; Compensated Liver Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Fibrosis regression rate

  20% decline in magnetic resonance elastography(MRE)

  72 weeks

Secondary Outcomes (12)

• Cumulative incidence of outcomes events

  72 weeks

• Percentage of participants acheving decline in fibrosis stage in histopathology

  72 weeks

• Number of patients with decreased scores of non-invasive liver fibrosis tests

  weeks 2, 4, 8, 12, 18, 24, 32, 40, 48, and 72.

• Number of patients with decrease of MRE

  weeks 48, and 72.

• Number of patients with change in magnetic resonance imaging-derived proton density fat fraction(MRI-PDFF))

  weeks 48, and 72.

Study Arms (2)

Treatment arm

EXPERIMENTAL

Chiglitazar 64mg, oral, qd, for 72 weeks

Drug: Chiglitazar 64mg

Control arm

PLACEBO COMPARATOR

Placebo, oral, qd, for 72 weeks

Drug: Placebo

Interventions

Chiglitazar 64mg DRUG

Chiglitazar 64mg, oral, qd, for 72 weeks

Treatment arm

Placebo DRUG

Placebo, oral, qd, for 72 weeks

Control arm

Eligibility Criteria

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

You may qualify if:

• \. Men and women aged between 18 and 75 years (inclusive) who understand and sign informed consent forms; 2. Compensated MAFLD-related cirrhosis diagnosis(meet one of the following conditions):
• The liver biopsy during the screening period (liver biopsy within 6 months of screening is acceptable) showing cirrhosis with steatohepatitis according to the Non Alcoholic Fatty Liver Disease Clinical Research Network (NASH-CRN) scoring system, and there is no evidence of competitive aetiology.
• The liver biopsy during the screening period (liver biopsy within 6 months of screening is acceptable) showing cirrhosis with steatosis (no steatohepatitis) according to NASH-CRN scoring system, and there is no evidence of competitive aetiology. There are at least 2 coexisting metabolic comorbidities or history of metabolic comorbidities, including obesity and/or type 2 diabetes mellitus (T2DM).
• Historical biopsy showed steatohepatitis, and now diagnosed with cirrhosis through non-invasive tests or clinical criteria (see criterion (5)-1)). There is no evidence of competing aetiology. There is at least 1 coexisting or history of metabolic comorbidity.
• Historical biopsy showed steatosis (no steatohepatitis), and now diagnosed with cirrhosis through non-invasive tests or clinical criteria (see criterion (5)-1)). There is no evidence of competing aetiology. There are at least 2 coexisting metabolic comorbidities or history of metabolic comorbidities, including obesity and/or T2DM.
• In the absence of biopsy, MAFLD-related cirrhosis is defined based on the following criterias:
• a. Cirrhosis is defined based on one of the following non-invasive tests(NITS): i: MRE ≥ 5kPa or VCTE-LSM ≥ 20kPa (when the patients with BMI ≥ 28kg/m2 , MRE ≥ 5kPa must also be met); ii:VCTE ≥15 kPa and \<20 kPa and 1 of the following: MRE≥4.45kPa or Agile4≥0.565 or Platelets≤150,000/µL; iii: VCTE \<15 kPa and 2 of the following: MRE≥4.45kPa or Agile4≥0.565 or Platelets≤150,000/µL; b. Current or previous imaging examinations have diagnosed fatty liver or controlled attenuation parameter (CAP)\>288dB/m or magnetic resonance imaging proton density fat fraction (MRI-PDFF)\>5%.
• c. There is no evidence of competing aetiology; d. There are at least 2 coexisting metabolic comorbidities or history of metabolic comorbidities, including obesity and/or T2DM.
• If a participant's MAFLD-related cirrhosis diagnosis for eligibility is based on the biopsy screening period , no weight loss of ≥10% should have occurred in the same time period (based on medical history).

You may not qualify if:

• Other chronic liver diseases (including but not limited to viral hepatitis, alcoholic liver disease, drug-induced liver injury, autoimmune liver disease, Wilson's disease, hemochromatosis, etc.)
• There has been a continuous history of heavy drinking for 3 months or more current or rencent 5 years (heavy drinking is defined as \>20 g/day in women and \>30 g/day in men); Or researchers can not reliably quantify alcohol consumption.
• Hepatic decompensation events (including ascites, esophageal and gastric variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, spontaneous bacterial peritonitis, etc.) or hepatocellular carcinomaor.
• History of malignant tumors within 5 years (excluding local squamous cell carcinoma of the skin or treated cervical intraepithelial neoplasia)；
• Combination of autoimmune diseases (including but not limited to systemic lupus erythematosus, multiple sclerosis, Hashimoto's thyroiditis, etc.)；
• Combined with severe esophageal and gastric varices and/or positive red sign accessed by endoscope；
• History of liver transplantation or bone marrow transplantationor or listed for liver transplantation;
• Previous (\<5 years before screening)or planned (during the trial period) treatment for obesity with surgery;
• Have obesity induced by other endocrinologic disorders (i.e. Cushing Syndrome) genetic diseases;
• Secondary factors that can cause liver steatosis, such as malnutrition, medication, genetic metabolic diseases, etc.
• Individuals with the following abnormal indicators:
• Alanine aminotransferase (ALT)\>5 \* ULN;
• Aspartate aminotransferase (AST)\>5 \* ULN
• Direct bilirubin (DBIL)\>1.5 \* ULN
• Estimated glomerular filtration rate (eGFR)\<60 mL/min/1.73m2

Sponsors & Collaborators

• Beijing Friendship Hospital: lead
• Beijing Ditan Hospital: collaborator
• Peking University People's Hospital: collaborator
• Beijing YouAn Hospital: collaborator

Study Sites (4)

Beijing Ditan Hospital, Capital Medical University

Beijing, China, 100015, China

Location

Peking University People's Hospital

Beijing, China, 100044, China

Location

Beijing Friendship Hospital, Capital Medical University

Beijing, China, 100050, China

Location

Beijing Youan Hospital, Capital Medical University

Beijing, China, 100069, China

Location

MeSH Terms

Interventions

chiglitazar

Central Study Contacts

Hong You

CONTACT

861063139019; youhong30@sina.com

Xiaofei Tong

CONTACT

Tongxf@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice president of hospital

Study Record Dates

• First Submitted: January 2, 2025
• First Posted: January 14, 2025
• Study Start: February 5, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: January 15, 2025

Record last verified: 2025-01

Locations

CN (4)