Non-Alcoholic Steatohepatitis (NASH) and F1-3 fibrosis. MedDRA version: 27.1 Level: LLT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Sponsors
CanFite BioPharma Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range 29
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Evaluate the efficacy of namodenoson as compared to placebo in subjects with NASH, as determined by the proportion of subjects who achieve a =2-point improvement in the non-alcoholic fatty liver disease (NAFLD) activity score (NAS) of the Non-Alcoholic Steatohepatitis Clinical Research Network (NASH CRN) (Kleiner 2005); and • Characterize the safety profile of namodenoson in subjects with NASH.;Secondary Objective: • Evaluate the efficacy of orally administered namodenoson in subjects with NASH, as determined by the mean Percent Change From Baseline (PCFB) in serum alanine aminotransferase (ALT) levels at Week 36; and • Assess the pharmacokinetics (PK) of namodenoson in this population.;Primary end point(s): Primary Efficacy Endpoint Primary efficacy Endpoint will be assessed through the proportion of subjects who achieve =2 point improvement in NASH histology on liver biopsy, using the NAS of the NASH CRN (Kleiner 2005). Primary Safety Endpoints Primary safety Endpoints will be assessed through the type, incidence, severity (graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0), timing, seriousness, and relationship to treatment of AEs.;Timepoint(s) of evaluation of this end point: Week 36 or Early termination (after at least 24 weeks of dosing) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary efficacy endpoint is the PCFB to Week 36 of serum ALT levels, defined as: PCFB = 100*[(Value at Week 36 – Value at Baseline) / Value at Baseline].;Timepoint(s) of evaluation of this end point: Week 36 | — |
Countries
Bosnia and Herzegovina, Bulgaria, Israel, Moldova, Republic of, Poland, Romania, Serbia
Contacts
Public ContactStudy Director
CanFite BioPharma Ltd.
Outcome results
None listed