A Phase II Clinical Trial of Chiglitazar for NASH

Phase 2

Completed

• Conditions: NASH
• Interventions: Drug: chiglitazar sodium tablets; Drug: Placebo

• Registration Number: NCT05193916
• Lead Sponsor: Chipscreen Biosciences, Ltd.

Brief Summary

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

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 Timeline

• Study First Submitted: 2021-12-03
• Study First Submitted QC: 2022-01-03
• Study First Posted: 2022-01-18
• Study Start: 2022-03-21
• Primary Completion: 2024-01-02
• Study Completion: 2024-01-02
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-24
• Last Update Posted: 2024-05-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 104

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chiglitazar low dose	chiglitazar sodium tablets	3 tablets of drug and 1 tablet of placebo p.o. per day
control group	Placebo	4 placebo tablets p.o. per day
Chiglitazar high dose	chiglitazar sodium tablets	4 tablets p.o. per day

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (15)

Foshan First People's Hospital; 🇨🇳 Foshan, Guangdong, China

Henan Provincial People's Hospital; 🇨🇳 Zhengzhou, Henan, China

The First Affiliated Hospital of Anhui Medical University; 🇨🇳 Hefei, Jiangsu, China

Beijing Friendship Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Peking University People's Hospital; 🇨🇳 Beijing, Beijing, China

Nanjing Second Hospital; 🇨🇳 Nanjing, Jiangsu, China

The First Hospital of Jilin University; 🇨🇳 Ch'ang-ch'un, Jilin, China

Shanghai Tongren Hospital; 🇨🇳 Shanghai, Shanghai, China

The First Affiliated Hospital of Xi'an Jiaotong University; 🇨🇳 Xi'an, Shaanxi, China

The Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China

Affiliated Hospital of Hangzhou Normal University; 🇨🇳 Hangzhou, Zhejiang, China

First Affiliated Hospital of Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China

The First Hospital of Lanzhou University; 🇨🇳 Lanzhou, Gansu, China

Beijing Youan Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

The First Affiliated Hospital of Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China