A Phase II Clinical Trial of Chiglitazar for NASH

• ClinicalTrials.gov Identifier: NCT05193916
• Recruitment Status: Recruiting
• First Posted: January 18, 2022
• Last Update Posted: August 28, 2023
• Sponsor: Chipscreen Biosciences, Ltd.
• Information provided by (Responsible Party): Chipscreen Biosciences, Ltd.

Tracking Information

• First Submitted Date: December 3, 2021
• First Posted Date: January 18, 2022
• Last Update Posted Date: August 28, 2023
• Actual Study Start Date: March 21, 2022
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 3, 2022)

Percentage change from baseline to week 18 in liver fat content as measured by MRI using the proton density fat fraction (MRI-PDFF) [ Time Frame: 18 weeks ]

center reading for the primary endpoint

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 22, 2022)

• the change in liver fat content from baseline as shown by MRI-PDFF after 18 weeks treatment [ Time Frame: 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
• ALT changes from baseline [ Time Frame: 6,12,18 weeks ]
  changes from baseline in liver enzymes
• FIB-4 changes from baseline [ Time Frame: 6,12,18 weeks ]
  changes from baseline in Fibrosis 4 Score
• insulin resistance changes [ Time Frame: 6,12,18 weeks ]
  Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
• Changes from baseline in TG [ Time Frame: 6,12,18 weeks ]
  blood sample
• change from baseline in Liver stiffness measurement (LSM) with Fibroscan [ Time Frame: 6,12,18 weeks ]
  to evlaute the severity of liver fibrosis
• change from baseline in Cytokeratin18 (CK-18) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 0, 6,12 weeks ]
  population PK

Original Secondary Outcome Measures (submitted: January 3, 2022)

• the change in liver fat content from baseline as shown by MRI-PDFF after 18 weeks treatment [ Time Frame: 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
• ALT changes from baseline [ Time Frame: 6,12,18 weeks ]
  changes from baseline in liver enzymes
• FIB-4 changes from baseline [ Time Frame: 6,12,18 weeks ]
  changes from baseline in Fibrosis 4 Score
• insulin resistance changes [ Time Frame: 6,12,18 weeks ]
  Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
• Changes from baseline in TG [ Time Frame: 6,12,18 weeks ]
  blood sample
• change from baseline in Liver stiffness measurement (LSM) with Fibroscan [ Time Frame: 6,12,18 weeks ]
  for liver fibrosis
• change from baseline in Cytokeratin18 (CK-18) [ Time Frame: 6,12,18 weeks ]
• Maximum Plasma Concentration [Cmax] of chiglitazar after 1 dose, 6 weeks and 12 weeks of treatment [ Time Frame: 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 [ Time Frame: 0, 6,12 weeks ]
  population PK

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: NASH

Intervention

• Drug: chiglitazar sodium tablets
  the drugs will be given orally once a day
  Other Names:

  • Bilessglu®
  • CS-038
  • Carfloglitazar
• Drug: Placebo
  no active drug contained
  Other Name: simulant of chiglitazar

Study Arms

• Experimental: Chiglitazar low dose
  3 tablets of drug and 1 tablet of placebo p.o. per day
  Intervention: Drug: chiglitazar sodium tablets
• Experimental: Chiglitazar high dose
  4 tablets p.o. per day
  Intervention: Drug: chiglitazar sodium tablets
• Placebo Comparator: control group
  4 placebo tablets p.o. per day
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 3, 2022): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2024
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Hong You, Phd; 86-10-63139019; youhong30@sina.com

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05193916
• Other Study ID Numbers: CGZ203; CINAR ( Other Identifier: Chipscreen )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Chipscreen Biosciences, Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Chipscreen Biosciences, Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Chipscreen Biosciences, Ltd.
• Verification Date: August 2023