Clinical trial NCT05193916: A Phase II Clinical Trial of Chiglitazar for NASH
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: NASH
Lead sponsor: Chipscreen Biosciences, Ltd.
Sponsor class: INDUSTRY
First posted: 2022-01-18
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage change from baseline to week 18 in liver fat content as measured by MRI using the proton density fat fraction (MRI-PDFF)
timeFrame: 18 weeks
Secondary outcomes:
measure: the change in liver fat content from baseline as shown by MRI-PDFF after 18 weeks treatment
timeFrame: 18 weeks
measure: ALT changes from baseline
timeFrame: 6,12,18 weeks
measure: FIB-4 changes from baseline
timeFrame: 6,12,18 weeks
measure: insulin resistance changes
timeFrame: 6,12,18 weeks
measure: Changes from baseline in TG
timeFrame: 6,12,18 weeks
measure: change from baseline in Liver stiffness measurement (LSM) with Fibroscan
timeFrame: 6,12,18 weeks
measure: change from baseline in Cytokeratin18 (CK-18)
timeFrame: 6,12,18 weeks
measure: Maximum Plasma Concentration [Cmax] of chiglitazar after 1 dose, 6 weeks and 12 weeks of treatment
timeFrame: 0, 6,12 weeks
measure: The area under the plasma drug concentration-time curve [AUC] of chiglitazar after 1 dose, 6 weeks and 12 weeks of treatment
timeFrame: 0, 6,12 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Youan Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Foshan
country: China
facility: Foshan First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Second Hospital
state: Jiangsu
city: Ch'ang-ch'un
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Shanghai
country: China
facility: Shanghai Tongren Hospital
state: Shanghai
city: Shanghai
country: China
facility: The Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Hangzhou
country: China
facility: Affiliated Hospital of Hangzhou Normal University
state: Zhejiang
city: Hangzhou
country: China
facility: First Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: