Namodenoson in the Treatment of Non-Alcoholic Steatohepatitis (NASH)

NCT ID: NCT04697810

Last Updated: 2024-07-31

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-10
• Study Completion Date: 2025-10-15

Brief Summary

Subjects with biopsy-proven NASH will be randomly assigned in a 2:1 ratio to oral doses of namodenoson 25 mg every 12 hours or matching placebo every 12 hours for 36 weeks. Subjects will be evaluated regularly for safety, and efficacy biomarkers will be measured at Baseline and Weeks 6, 12, 24, and 36. At Week 36, all subjects will undergo liver biopsy.

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled study in subjects with a diagnosis of NASH and F1-3 fibrosis. Subjects will undergo Screening procedures during the 6 weeks preceding Baseline. Subjects (n = ~114) will be randomly assigned in a 2:1 ratio to oral doses of namodenoson 25 mg every 12 hours or matching placebo every 12 hours for 36 weeks. Subjects will be evaluated regularly for safety, and efficacy biomarkers will be measured at Baseline and Weeks 6, 12, 24, and 36. At Week 36, all subjects will undergo post-treatment liver biopsy, which will be interpreted by a blinded expert hepatopathologist. Subjects will return for a follow-up visit 6 weeks after completion of the last dose of study drug.

Conditions

NASH - Nonalcoholic Steatohepatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Namodenoson

Namodenoson capsules orally 25 mg every 12 hours for 36 weeks

Group Type: EXPERIMENTAL

Namodenoson

Intervention Type: DRUG

25 mg q12hours x 36 weeks

Placebo

Matching placebo capsules orally 25 mg every 12 hours for 36 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching capsules q12hours x 36 weeks

Interventions

Namodenoson

25 mg q12hours x 36 weeks

Intervention Type: DRUG

Placebo

Matching capsules q12hours x 36 weeks

Intervention Type: DRUG

Other Intervention Names

CF102; Inactive control

Eligibility Criteria

Inclusion Criteria

1. At least 18 years of age.

2. AST at Screening of ≥20 IU/L.

3. FibroScan LSM ≥8.5 kPa

4. 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 and the slides are available for central read prior to randomization, this biopsy can be waived.

5. Concomitant biopsy-proven Stage 1-3 hepatic fibrosis by NASH CRN criteria by central read (Kleiner 2005).

6. At least 2 of the following criteria for the metabolic syndrome:

• Obesity, defined waist circumference >88 cm for women or >102 cm for men
• Hypertriglyceridemia, defined as >150 mg/dL (>1.7 mmol/L) or on drug treatment for hypertriglyceridemia
• Reduced high-density lipoprotein (HDL) cholesterol, defined as <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).

7. Acceptable hepatic metabolic and synthetic function, as indicated at Screening by:

• Serum albumin ≥3.5 gm/dL
• International normalized ratio ≤1.3
• Serum total bilirubin ≤2.0 mg/dL (unless subject has known Gilbert's Syndrome).

8. The following laboratory values must be documented at Screening:

• Absolute neutrophil count at least 1.0 x 109/L
• Platelet count at least 150 x 109/L
• Estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m2

9. Female subjects may be enrolled if they are not of childbearing potential, permanently sterile or are post-menopausal, defined as no menses for at least 1 year without an alternative medical cause and FSH levels in the post-menopausal range.

10. Male subjects must refrain from sperm donation during treatment and until at least 90 days after the end of study drug dosing. Male subjects with fertile or pregnant partners must agree to use condoms throughout the course of the trial and for 3 months after.

11. Patients taking herbal supplements, homeopathic medications, or other alternative treatments, must be on a stable regimen for at least 3 months prior to randomization.

12. Understand and provide written informed consent to participate.

13. Willing to undergo 2 liver biopsies.

14. Willing to comply with scheduled visits, treatment plans, laboratory assessments, and other study-related procedures.

Exclusion Criteria

1. 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.

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)/day for women and 30 g (3 units)/day for men (on average), as per Alcohol Use Disorders Identification Test (AUDIT) questionnaire.

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.

11. Active rheumatoid arthritis treated with small-molecule (including methotrexate) or biologic disease-modifying anti-rheumatic agent concurrently or within 1 year.

12. Use of any immunosuppressive medication, anti-inflammatory monoclonal antibody treatment, or chronic systemic corticosteroids >10 mg prednisone-equivalent concurrently or within 1 year.

13. More than 7 days of treatment with valproic acid, tamoxifen, amiodarone, or anti-cholinergic agents within 3 months.

14. Uncontrolled or clinically unstable thyroid disease.

15. 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.

16. Angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months.

17. QTcF interval on Screening Visit ECG or an average of triplicate Baseline Visit ECGs > 450 milliseconds (msec) for males or > 470 msec for females.

18. A condition which increases proarrhythmic risk, including hypokalemia, hypomagnesemia, or congenital Long QT Syndrome.

19. Ongoing or planned use of a concomitant medication that is on the CredibleMedsTM list of drugs known to cause Torsades des Pointes.

20. Active gastrointestinal disease which could interfere with the absorption of oral medication.

21. Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that would make the patient inappropriate for entry into this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Can-Fite BioPharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael H Silverman, MD

Role: STUDY_DIRECTOR

BioStrategics Consulting Ltd

Locations

941 Univ of Clinical Centre of the Republic of Srpska

Banja Luka, , Bosnia and Herzegovina

Site Status: NOT_YET_RECRUITING

942 Health Inst General Hospital, Dept of Internal Medicine

Prijedor, , Bosnia and Herzegovina

Site Status: NOT_YET_RECRUITING

934 Second Dept of Internal Disease, MHAT Sveta Karidad EAD

Plovdiv, , Bulgaria

Site Status: NOT_YET_RECRUITING

932 Office of Gastroenterology, Medical Center Sansi EOOD

Rousse, , Bulgaria

Site Status: NOT_YET_RECRUITING

931 Clinic of Gastroenterology, Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda EAD, Sofia

Sofia, , Bulgaria

Site Status: NOT_YET_RECRUITING

933 Clinic of Gastroenterology, University Multiprofile Hosptial for Active Treatment

Sofia, , Bulgaria

Site Status: NOT_YET_RECRUITING

935 Dept of Gastroent., Univ Multiprofile Hospital for Active Treatment and Emergency Medicine

Sofia, , Bulgaria

Site Status: NOT_YET_RECRUITING

936 Office of Gastroenterology, Diagnostic - Consultative Center XX

Sofia, , Bulgaria

Site Status: NOT_YET_RECRUITING

937 Office of Gastroenterology, Diagnostic - Consultative Center Alexandrovska

Sofia, , Bulgaria

Site Status: NOT_YET_RECRUITING

938 Clinic of Gastroenterology, University Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski"

Sofia, , Bulgaria

Site Status: NOT_YET_RECRUITING

517 Saroka University Medical Center

Beersheba, , Israel

Site Status: RECRUITING

Hadassah Medical Center

Jerusalem, , Israel

Site Status: ACTIVE_NOT_RECRUITING

911 IMSP Spitalul Clinic Republican "Timofei Mosneaga"

Chisinau, , Moldova

Site Status: RECRUITING

912 SP Spitalul Ministerului Sanatatii, Muncii si Protectiei Sociale

Chisinau, , Moldova

Site Status: NOT_YET_RECRUITING

903 Central Pentru Studiul Metabolismului

Bucharest, , Romania

Site Status: RECRUITING

904 SUUMC Carol Davilla, Department Diabet

Bucharest, , Romania

Site Status: RECRUITING

906 Spitalul Sfanta Maria

Bucharest, , Romania

Site Status: RECRUITING

902 Cluj County Clinical Emergency Hospital, 3rd Dept of Internal Medicine

Cluj-Napoca, , Romania

Site Status: RECRUITING

901 Medical Center Dr. Ianosi

Craiova, , Romania

Site Status: RECRUITING

905 County Hospital Timisoara

Timișoara, , Romania

Site Status: RECRUITING

922 UCC Zvezdara Belgrade

Belgrade, , Serbia

Site Status: NOT_YET_RECRUITING

923 Military Medical Academy Belgrade

Belgrade, , Serbia

Site Status: NOT_YET_RECRUITING

924 CHC "dr Dragisa Misovic" - Dedinje Belgrade

Belgrade, , Serbia

Site Status: NOT_YET_RECRUITING

921 UCC Nis

Niš, , Serbia

Site Status: NOT_YET_RECRUITING

Countries

Bosnia and Herzegovina; Bulgaria; Israel; Moldova; Romania; Serbia

Central Contacts

Zivit Harpaz

Role: CONTACT

Zivit@canfite.co.il

+972-3-9241114

Pnina Fishman, PhD

Role: CONTACT

pnina@canfite.co.il

+972-3-9241114

Facility Contacts

Study Coordinator

Role: primary

Study Coordinator

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Study Coordinator

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Study Coordinator

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Study Coordinator

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Study Coordinator

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Study Coordinator

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Study Coordinator

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Study Coordinator

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Study Coordinator

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Hoad Etzion, MD

Role: primary

Eugen Tcaciuc

Role: primary

Study Coordinator

Role: primary

Study Coordinator

Role: primary

Study Coordinator

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Study Coordinator

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Study Coordinator

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Study Coordinator

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Study Coordinator

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Study Coordinator

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Study Coordinator

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Study Coordinator

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Study Coordinator

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References

Cohen S, Stemmer SM, Zozulya G, Ochaion A, Patoka R, Barer F, Bar-Yehuda S, Rath-Wolfson L, Jacobson KA, Fishman P. CF102 an A3 adenosine receptor agonist mediates anti-tumor and anti-inflammatory effects in the liver. J Cell Physiol. 2011 Sep;226(9):2438-47. doi: 10.1002/jcp.22593.

Reference Type: BACKGROUND

PMID: 21660967 (View on PubMed)

Safadi R, Braun M, Francis A, Milgrom Y, Massarwa M, Hakimian D, Hazou W, Issachar A, Harpaz Z, Farbstein M, Itzhak I, Lev-Cohain N, Bareket-Samish A, Silverman MH, Fishman P. Randomised clinical trial: A phase 2 double-blind study of namodenoson in non-alcoholic fatty liver disease and steatohepatitis. Aliment Pharmacol Ther. 2021 Dec;54(11-12):1405-1415. doi: 10.1111/apt.16664. Epub 2021 Oct 20.

Reference Type: BACKGROUND

PMID: 34671996 (View on PubMed)

Related Links

https://www.canfite.com/

Sponsor website

Other Identifiers

CF102-212LD

Identifier Type: -

Identifier Source: org_study_id