A Phase 2B Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Namodenoson in the Treatment of Non-Alcoholic Steatohepatitis (NASH)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Can-Fite Biopharma Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

2 Mar 2023 → ongoing

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Can-Fite BioPharma, Ltd.

External identifiers

EU CT number

2023-510548-19-00

EudraCT number

2021-005245-32

ClinicalTrials.gov

NCT04697810

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Efficacy, Safety

• 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)
• Characterize the safety profile of namodenoson in subjects with NASH.

Secondary objectives 2

1. 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.
2. Assess the pharmacokinetics (PK) of namodenoson in this population.

Conditions and MedDRA coding

Non-Alcoholic Steatohepatitis (NASH) with F1-3 fibrosis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

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

Exclusion criteria 27

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 who partner with a woman of childbearing potential, unless they agree to use effective, dual contraceptive methods (i.e., a condom, with female partner using oral, injectable, or barrier method) while on study drug and for 3 months afterward
24. A condition which increases proarrhythmic risk, including hypokalemia, hypomagnesemia, or congenital Long QT Syndrome
25. Ongoing or planned use of a concomitant medication that is on the CredibleMedsTM list of drugs known to cause Torsades des Pointes (Appendix 1)
26. Active gastrointestinal disease which could interfere with the absorption of oral medication
27. Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with the interpretation of study results and, in the investigator’s opinion, would make the patient inappropriate for entry into this study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of subjects who achieve a ≥2-point improvement in NAS (Week 36, relative to Baseline)

Secondary endpoints 1

1. The mean PCFB in serum ALT level (Week 36, relative to Baseline)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Can-Fite Biopharma Ltd.

Sponsor organisation

Can-Fite Biopharma Ltd.

Address

Kiryat Matalon, 10, Bareket 10, Bareket

City

Petakh Tikva

Postcode

4951778

Country

Israel

Scientific contact point

Organisation

Can-Fite Biopharma Ltd.

Contact name

Zivit Harpaz

Public contact point

Organisation

Can-Fite Biopharma Ltd.

Contact name

Zivit Harpaz

Third parties 5

Locations

3 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 57 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications