A Phase II Clinical Trial of Chiglitazar for NASH

A Multi-Center, Randomised, Double-blind, Placebo Controlled Phase II Clinical Study of Chiglitazar in Patients With Nonalcoholic Steatohepatitis Accompanied by Elevated Triglycerides and Insulin Resistance

The study is to evaluate the efficacy and safety of chiglitazar monotherapy in patients with non-clcoholic steatohepatitis (NASH).

Study Overview

• Status: Completed
• Conditions: NASH
• Intervention / Treatment: Drug: chiglitazar sodium tablets; Drug: Placebo

Detailed Description

The study is a non-invasive exploratory phase II trial in patients who were clinically diagnosed as non-alcoholic steatohepatitis (NASH) with liver fibrosis accompanied by elevated triglycerides (TG) and insulin resistance. The efficacy and safety of chiglitazar tablets 48mg and 64mg will be compared with placebo in the 18-week-treament.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China
      • Beijing Youan Hospital, Capital Medical University
    • Beijing, Beijing, China
      • Peking University People's Hospital
  • Gansu
    • Lanzhou, Gansu, China
      • The First Hospital of Lanzhou University
  • Guangdong
    • Foshan, Guangdong, China
      • Foshan First People's Hospital
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Sun Yat-sen University
  • Henan
    • Zhengzhou, Henan, China
      • Henan Provincial People's Hospital
  • Jiangsu
    • Hefei, Jiangsu, China
      • The First Affiliated Hospital of Anhui Medical University
    • Nanjing, Jiangsu, China
      • Nanjing Second Hospital
  • Jilin
    • Ch'ang-ch'un, Jilin, China
      • The First Hospital of Jilin University
  • Shaanxi
    • Xi'an, Shaanxi, China
      • The First Affiliated Hospital Of Xi'an Jiaotong University
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Tongren Hospital
    • Shanghai, Shanghai, China
      • The Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • First Affiliated Hospital of Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China
      • Affiliated Hospital of Hangzhou Normal University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Before any evaluation, an informed consent form voluntarily signed by the patient must be obtained;
2. 18 -75 years old (at the time of screening visit V1), male or female;
3. MRI-PDFF ≥ 8% ;
4. Liver stiffness value ( LSM ) 7.0-11.0kPa ;
5. Triglyceride ( TG ) ≥1.7mmol/L and ≤5.6 mmol/L;
6. HOMA-IR ≥ 2.5 ;
7. Serum Alanine aminotransferease (ALT) ≥ the upper limit of normal during screening.

Exclusion Criteria:

1. Type 1 diabetes;

2. Any of the following for type 2 diabetes:

   • HbA1c ≥ 8.5% during screening
   • At the time of screening, ≥ 2 oral hypoglycemic drugs combinations
   • Receiving any of the following medications at screening: Thiazolidinediones (TZD) drugs, fibrates, glucagon-like peptide-1 (GLP-1) receptor agonists, insulin
3. Existing other liver diseases or history of liver diseases
4. History of transient ischemic attack or cerebrovascular accident;
5. History of myocardial infarction, or coronary angioplasty or coronary artery bypass surgery, unstable angina, heart failure (New York Heart Association NYHA grade III / IV ), or ECG signs of left ventricular hypertrophy, or serious arrhythmias ；
6. During screening, blood pressure ≥ 160/100 mmHg ;
7. Previous or planned ( during the study period) bariatric surgery;
8. Liver transplantation history or planned liver transplantation;
9. Liver biopsy show liver cirrhosis or clinically diagnosed as cirrhosis;
10. Weight loss of more than 5% in 6 months before screening;
11. History of edema of lower limbs or whole body;
12. diagnosed as osteoporosis or any other known bone disease;
13. Donated blood or lost blood >400 ml within 8 weeks before the first medication;
14. With MRI scan contraindications;
15. In the past 5 years, there was a history of malignant tumors of any organ system;
16. Human immunodeficiency virus ( HIV ) test is positive;
17. Heavy drinking of alcohol for more than 3 months in a year;
18. Heavy smoking >30 per day within 1 year;
19. History of drug abuse in 12 months;
20. Drugs cumulatively for more than 1 month in the previous 3 months before screening, such as obeticholic acid ( OCA ), berberine;
21. Drugs that may cause liver damage for more than 2 weeks within 1 year before screening;
22. Patients received the following medications unless they have received a stable dose for at least 1 month before screening :Beta-blockers, thiazide diuretics, statins, niacin, ezetimibe, thyroid hormone;
23. The calculated eGFR < 60 mL/(min*1.73m^2 );
24. There is clinical evidence of liver decompensation or severe liver damage;
25. Low density lipoprotein cholesterol (LDL-C) ≥ 3.4 mmol/L during screening ;
26. Platelet < 100×10^9 /L ;
27. Patient participating in other clinical trials of drugs or medical devices within 3 months prior to screening ;
28. Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chiglitazar low dose; 3 tablets of drug and 1 tablet of placebo p.o. per day	Drug: chiglitazar sodium tablets; the drugs will be given orally once a day; Other Names: Bilessglu®; CS-038; Carfloglitazar
Experimental: Chiglitazar high dose; 4 tablets p.o. per day	Drug: chiglitazar sodium tablets; the drugs will be given orally once a day; Other Names: Bilessglu®; CS-038; Carfloglitazar
Placebo Comparator: control group; 4 placebo tablets p.o. per day	Drug: Placebo; no active drug contained; Other Names: simulant of chiglitazar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change from baseline to week 18 in liver fat content as measured by MRI using the proton density fat fraction (MRI-PDFF)	center reading for the primary endpoint	18 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the change in liver fat content from baseline as shown by MRI-PDFF after 18 weeks treatment	Absolute decrease in liver fat content Proportion of patients with Liver fat content absolute decrease ≥5% Proportion of patients with Liver fat content relative decrease ≥30% proportion	18 weeks
ALT changes from baseline	changes from baseline in liver enzymes	6,12,18 weeks
FIB-4 changes from baseline	changes from baseline in Fibrosis 4 Score	6,12,18 weeks
insulin resistance changes	Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)	6,12,18 weeks
Changes from baseline in TG	blood sample	6,12,18 weeks
change from baseline in Liver stiffness measurement (LSM) with Fibroscan	to evlaute the severity of liver fibrosis	6,12,18 weeks
change from baseline in Cytokeratin18 (CK-18)	to evaluate the severity of liver damage	6,12,18 weeks
Maximum Plasma Concentration [Cmax] of chiglitazar after 1 dose, 6 weeks and 12 weeks of treatment	population PK	0, 6,12 weeks
The area under the plasma drug concentration-time curve [AUC] of chiglitazar after 1 dose, 6 weeks and 12 weeks of treatment	population PK	0, 6,12 weeks

Collaborators and Investigators

• Sponsor: Chipscreen Biosciences, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2022
• Primary Completion (Actual): January 2, 2024
• Study Completion (Actual): January 2, 2024

Study Registration Dates

• First Submitted: December 3, 2021
• First Submitted That Met QC Criteria: January 3, 2022
• First Posted (Actual): January 18, 2022

Study Record Updates

• Last Update Posted (Actual): May 28, 2024
• Last Update Submitted That Met QC Criteria: May 24, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: CGZ203; CINAR (Other Identifier: Chipscreen)

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