Clinical trial in subjects with Non-Alcoholic Steatohepatitis and fibrosis, diagnosed by liver biopsy.

Phase 1

• Conditions: on-Alcoholic Steatohepatitis (NASH) and F1-3 fibrosis.; MedDRA version: 24.1Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2021-005245-32-BG
• Lead Sponsor: CanFite BioPharma Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2023-05-18
• Last Update Posted: 18 September 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 129

Inclusion Criteria

1. At least 18 years of age.
2. AST at Screening of =20 IU/L.
3. Diagnosis of NASH by biopsy at Screening showing NAS =4 by
central read, with a score of at least 1 point in each of the 3 histologic
categories of steatosis, inflammation, and hepatocellular ballooning
(Kleiner 2005). If the subject has had a qualifying liver biopsy within
6 months prior to Baseline, this biopsy can be waived as long as the
slides are available for the central read prior to randomization
(Section 12.4.9).
4. Concomitant biopsy-proven Stage 1-3 hepatic fibrosis by NASH CRN criteria by central read (Kleiner 2005).
5. At least 2 of the following criteria for the metabolic syndrome (Grundy 2005):
• Obesity, defined as waist circumference >88 cm for women or >102 cm for men
• Hypertriglyceridemia, defined as triglycerides >150 mg/dL (>1.7 mmol/L) or on drug treatment for hypertriglyceridemia
• Reduced high-density lipoprotein (HDL) cholesterol, defined as HDL cholesterol <40 mg/dL (<1.03 mmol/L) in men or <50 mg/dL (<1.3 mmol/L) in women
• History of hypertension, currently controlled in the judgment of the Investigator
• Elevated fasting glucose, defined as =100 mg/dL (=5.6 mmol/L).
6. Acceptable hepatic metabolic and synthetic function, as indicated at Screening by:
• Serum albumin =3.5 gm/dL
• International normalized ratio (INR) =1.3
• Serum total bilirubin =2.0 mg/dL (unless subject has known Gilbert’s Syndrome).
7. The following laboratory values must be documented at Screening:
• Absolute neutrophil count =1.0 x 109/L
• Platelet count =150 x 109/L
• Estimated glomerular filtration rate (eGFR) =50 mL/min/1.73m2
8. Patients taking herbal supplements, homeopathic medications, or other alternative treatments must be on a stable regimen for at least 3 months prior to randomization.
9. Understand and provide written informed consent to participate.
10. Willing to undergo 2 liver biopsies.
11. Willing to comply with scheduled visits, treatment plans, laboratory assessments, and other study-related procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 29

Exclusion Criteria

1. Presence of ascites, hepatic encephalopathy, or other clinical evidence of cirrhosis.
2. Other active acute or chronic liver disease, such as autoimmune hepatitis, hepatitis B, hepatitis C, alcoholic liver disease, or hepatocellular carcinoma.
3. Seropositivity for markers of viral hepatitis or human immunodeficiency virus (HIV) at Screening. (Notes: If anti-hepatitis C virus (HCV) antibody is positive, a negative HCV ribonucleic acid (RNA) test is required for entry. Any prior treatment for HCV must have been completed at least 2 years prior to the qualifying liver biopsy.)
4. Weight loss of >5% within 3 months prior to Baseline.
5. History of bariatric surgery within 5 years of Screening.
6. Diabetes mellitus other than Type II.
7. Hemoglobin A1c >9.0% (subjects with diabetes).
8. Any contraindication to percutaneous liver biopsy.
9. Daily alcohol intake >20 g (2 units=2 standard drinks)/day for women and 30 g (3 units=3 standard drinks)/day for men (on average), as per Alcohol Use Disorders Identification Test (AUDIT) questionnaire at Screening or Baseline.
10. Treatment with therapeutic doses of Vitamin E (=800-1000 IU daily), or any of the following anti-diabetic medications: GLP-1 receptor agonists (such as Januvia [sitagliptin], Byetta [incretin], etc.), pioglitazone, or SGLT2 inhibitors (gliflozin” drugs); unless the dose and regimen has been stable for at least 3 months prior to Screening.
11. Active rheumatoid arthritis treated with small-molecule (including methotrexate) or biologic disease-modifying anti-rheumatic agent concurrently or within 1 year prior to Screening.
12. Use of any immunosuppressive medication, anti-inflammatory monoclonal antibody treatment, or chronic systemic corticosteroids >10 mg prednisone-equivalent concurrently or within 1 year prior to Screening.
13. More than 7 days of treatment with valproic acid, tamoxifen, amiodarone, or anti-cholinergic agents within 3 months prior to Screening.
14. Use of any investigational agent within 4 weeks prior to the Baseline Visit.
15. Concomitant use of P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) inhibitors and/or substrates with a narrow therapeutic index unless the medication can be taken at least 3 hours before or after taking the investigational product (see Section 12.2).
16. Uncontrolled or clinically unstable thyroid disease, in the judgment of the Principal Investigator.
17. Concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy.
18. Uncontrolled arterial hypertension or congestive heart failure (New York Heart Association Classification 3 or 4), or other heart disease which is, in the Investigator’s judgment, clinically unstable.
19. Angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.
20. QTcF interval on Screening Visit ECG (average of triplicate) or an average of triplicate Baseline Visit ECGs > 450 milliseconds (msec) for males or > 470 msec for females (except when QT prolongation is associated with right or left bundle branch block, in which case enrollment is allowed).
21. Pregnant or lactating female.
22. Women of childbearing potential (WOCBP), unless they agree to use dual contraceptive methods which, in the opinion of the Investigator, are effective and adequate for the patient’s circumstances while on study drug.
23. Men

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified