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

NCT04697810 | Recruiting Phase 2

• 1 other identifier: CF102-212LD
• Study Type: interventional
• Target: 114
• Locations: 6 countries
• Sites: 24

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.

Conditions

NASH - Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (2)

• Non-Alcoholic Fatty Liver Disease (NAFLD) activity score (NAS)

  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)

  36 weeks

• Adverse events (AEs)

  Incidence of AEs

  36 weeks

Secondary Outcomes (2)

• Alanine transaminase (ALT) mean

  36 weeks

• Steady-state blood level of namodenoson

  36 weeks

Other Outcomes (13)

• ALT absolute

  36 weeks

• ALT threshold

  36 weeks

• Weight

  36 weeks

Study Arms (2)

Namodenoson

EXPERIMENTAL

Namodenoson capsules orally 25 mg every 12 hours for 36 weeks

Drug: Namodenoson

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Namodenoson DRUG

25 mg q12hours x 36 weeks

Also known as: CF102

Namodenoson

Placebo DRUG

Matching capsules q12hours x 36 weeks

Also known as: Inactive control

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age.
• AST at Screening of ≥20 IU/L.
• FibroScan LSM ≥8.5 kPa
• 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.
• Concomitant biopsy-proven Stage 1-3 hepatic fibrosis by NASH CRN criteria by central read (Kleiner 2005).
• 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).
• 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).

You may not qualify if:

• Ascites, hepatic encephalopathy, or other clinical evidence of cirrhosis.
• Other active acute or chronic liver disease, such as autoimmune hepatitis, hepatitis B, hepatitis C, alcoholic liver disease, or hepatocellular carcinoma.
• Seropositivity for markers of viral hepatitis or human immunodeficiency virus (HIV) at Screening.
• Weight loss of \>5% within 3 months prior to Baseline.
• History of bariatric surgery within 5 years of Screening.
• Diabetes mellitus other than Type II.
• Hemoglobin A1c \>9.0% (subjects with diabetes).
• Any contraindication to percutaneous liver biopsy.
• 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.
• 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.
• Active rheumatoid arthritis treated with small-molecule (including methotrexate) or biologic disease-modifying anti-rheumatic agent concurrently or within 1 year.
• Use of any immunosuppressive medication, anti-inflammatory monoclonal antibody treatment, or chronic systemic corticosteroids \>10 mg prednisone-equivalent concurrently or within 1 year.
• More than 7 days of treatment with valproic acid, tamoxifen, amiodarone, or anti-cholinergic agents within 3 months.
• Uncontrolled or clinically unstable thyroid disease.
• 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.

Sponsors & Collaborators

• Can-Fite BioPharma: lead

Study Sites (24)

941 Univ of Clinical Centre of the Republic of Srpska

Banja Luka, Bosnia and Herzegovina

NOT YET RECRUITING

942 Health Inst General Hospital, Dept of Internal Medicine

Prijedor, Bosnia and Herzegovina

NOT YET RECRUITING

934 Second Dept of Internal Disease, MHAT Sveta Karidad EAD

Plovdiv, Bulgaria

NOT YET RECRUITING

932 Office of Gastroenterology, Medical Center Sansi EOOD

Rousse, Bulgaria

NOT YET RECRUITING

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

Sofia, Bulgaria

NOT YET RECRUITING

933 Clinic of Gastroenterology, University Multiprofile Hosptial for Active Treatment

Sofia, Bulgaria

NOT YET RECRUITING

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

Sofia, Bulgaria

NOT YET RECRUITING

936 Office of Gastroenterology, Diagnostic - Consultative Center XX

Sofia, Bulgaria

NOT YET RECRUITING

937 Office of Gastroenterology, Diagnostic - Consultative Center Alexandrovska

Sofia, Bulgaria

NOT YET RECRUITING

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

Sofia, Bulgaria

NOT YET RECRUITING

517 Saroka University Medical Center

Beersheba, Israel

RECRUITING

Hadassah Medical Center

Jerusalem, 91120, Israel

ACTIVE NOT RECRUITING

911 IMSP Spitalul Clinic Republican "Timofei Mosneaga"

Chisinau, Moldova

RECRUITING

912 SP Spitalul Ministerului Sanatatii, Muncii si Protectiei Sociale

Chisinau, Moldova

NOT YET RECRUITING

903 Central Pentru Studiul Metabolismului

Bucharest, Romania

RECRUITING

904 SUUMC Carol Davilla, Department Diabet

Bucharest, Romania

RECRUITING

906 Spitalul Sfanta Maria

Bucharest, Romania

RECRUITING

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

Cluj-Napoca, Romania

RECRUITING

901 Medical Center Dr. Ianosi

Craiova, Romania

RECRUITING

905 County Hospital Timisoara

Timișoara, Romania

RECRUITING

922 UCC Zvezdara Belgrade

Belgrade, Serbia

NOT YET RECRUITING

923 Military Medical Academy Belgrade

Belgrade, Serbia

NOT YET RECRUITING

924 CHC "dr Dragisa Misovic" - Dedinje Belgrade

Belgrade, Serbia

NOT YET RECRUITING

921 UCC Nis

Niš, Serbia

NOT YET RECRUITING

Related Publications (2)

• 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.

  PMID: 21660967 BACKGROUND

• 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.

  PMID: 34671996 BACKGROUND

Related Links

• Sponsor website

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Michael H Silverman, MD

  BioStrategics Consulting Ltd

  STUDY DIRECTOR

Central Study Contacts

Zivit Harpaz

CONTACT

+972-3-9241114; Zivit@canfite.co.il

Pnina Fishman, PhD

CONTACT

+972-3-9241114; pnina@canfite.co.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo capsules are identical in appearance to namodenoson capsules.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomly assigned in a 2:1 ratio of namodenoson 25 mg or matching placebo, according to a computer-generated randomization schedule. Blocked randomization will be programmed using a pre-specified block size. Double-blinding will be maintained throughout the trial.

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 6, 2021
• Study Start: December 10, 2021
• Primary Completion: April 15, 2025
• Study Completion: October 15, 2025
• Last Updated: July 31, 2024

Record last verified: 2024-07

Locations

SE (4); IL (2); BU (8); MO (2); BO (2); RO (6)