- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04697810
Namodenoson in the Treatment of Non-Alcoholic Steatohepatitis (NASH)
June 15, 2023 updated by: Can-Fite BioPharma
A Phase 2B Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Namodenoson in the Treatment of Non-Alcoholic Steatohepatitis (NASH)
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Estimated)
114
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Zivit Harpaz
- Phone Number: +972-3-9241114
- Email: Zivit@canfite.co.il
Study Contact Backup
- Name: Pnina Fishman, PhD
- Phone Number: +972-3-9241114
- Email: pnina@canfite.co.il
Study Locations
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Banja Luka, Bosnia and Herzegovina
- Not yet recruiting
- 941 Univ of Clinical Centre of the Republic of Srpska
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Contact:
- Study Coordinator
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Prijedor, Bosnia and Herzegovina
- Not yet recruiting
- 942 Health Inst General Hospital, Dept of Internal Medicine
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Contact:
- Study Coordinator
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Plovdiv, Bulgaria
- Not yet recruiting
- 934 Second Dept of Internal Disease, MHAT Sveta Karidad EAD
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Contact:
- Study Coordinator
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Ruse, Bulgaria
- Not yet recruiting
- 932 Office of Gastroenterology, Medical Center Sansi EOOD
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Contact:
- Study Coordinator
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Sofia, Bulgaria
- Not yet recruiting
- 931 Clinic of Gastroenterology, Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda EAD, Sofia
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Contact:
- Study Coordinator
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Sofia, Bulgaria
- Not yet recruiting
- 933 Clinic of Gastroenterology, University Multiprofile Hosptial for Active Treatment
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Contact:
- Study Coordinator
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Sofia, Bulgaria
- Not yet recruiting
- 935 Dept of Gastroent., Univ Multiprofile Hospital for Active Treatment and Emergency Medicine
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Contact:
- Study Coordinator
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Sofia, Bulgaria
- Not yet recruiting
- 936 Office of Gastroenterology, Diagnostic - Consultative Center XX
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Contact:
- Study Coordinator
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Sofia, Bulgaria
- Not yet recruiting
- 937 Office of Gastroenterology, Diagnostic - Consultative Center Alexandrovska
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Contact:
- Study Coordinator
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Sofia, Bulgaria
- Not yet recruiting
- 938 Clinic of Gastroenterology, University Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski"
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Contact:
- Study Coordinator
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Be'er Sheva, Israel
- Recruiting
- 517 Saroka University Medical Center
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Contact:
- Hoad Etzion, MD
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Jerusalem, Israel, 91120
- Active, not recruiting
- Hadassah Medical Center
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Chisinau, Moldova, Republic of
- Recruiting
- 911 IMSP Spitalul Clinic Republican "Timofei Mosneaga"
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Contact:
- Eugen Tcaciuc
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Chisinau, Moldova, Republic of
- Not yet recruiting
- 912 SP Spitalul Ministerului Sanatatii, Muncii si Protectiei Sociale
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Contact:
- Study Coordinator
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Bucharest, Romania
- Recruiting
- 903 Central Pentru Studiul Metabolismului
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Contact:
- Study Coordinator
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Bucharest, Romania
- Recruiting
- 904 SUUMC Carol Davilla, Department Diabet
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Contact:
- Study Coordinator
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Bucharest, Romania
- Recruiting
- 906 Spitalul Sfanta Maria
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Contact:
- Study Coordinator
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Cluj-Napoca, Romania
- Recruiting
- 902 Cluj County Clinical Emergency Hospital, 3rd Dept of Internal Medicine
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Contact:
- Study Coordinator
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Craiova, Romania
- Recruiting
- 901 Medical Center Dr. Ianosi
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Contact:
- Study Coordinator
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Timişoara, Romania
- Recruiting
- 905 County Hospital Timisoara
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Contact:
- Study Coordinator
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Belgrade, Serbia
- Not yet recruiting
- 922 UCC Zvezdara Belgrade
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Contact:
- Study Coordinator
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Belgrade, Serbia
- Not yet recruiting
- 923 Military Medical Academy Belgrade
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Contact:
- Study Coordinator
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Belgrade, Serbia
- Not yet recruiting
- 924 CHC "dr Dragisa Misovic" - Dedinje Belgrade
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Contact:
- Study Coordinator
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Niš, Serbia
- Not yet recruiting
- 921 UCC Nis
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Contact:
- Study Coordinator
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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).
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
- 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.
- 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.
- Patients taking herbal supplements, homeopathic medications, or other alternative treatments, must be on a stable regimen for at least 3 months prior to randomization.
- Understand and provide written informed consent to participate.
- Willing to undergo 2 liver biopsies.
- Willing to comply with scheduled visits, treatment plans, laboratory assessments, and other study-related procedures.
Exclusion Criteria:
- 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.
- Angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months.
- QTcF interval on Screening Visit ECG or an average of triplicate Baseline Visit ECGs > 450 milliseconds (msec) for males or > 470 msec for females.
- A condition which increases proarrhythmic risk, including hypokalemia, hypomagnesemia, or congenital Long QT Syndrome.
- Ongoing or planned use of a concomitant medication that is on the CredibleMedsTM list of drugs known to cause Torsades des Pointes.
- Active gastrointestinal disease which could interfere with the absorption of oral medication.
- Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that would make the patient inappropriate for entry into this study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Namodenoson
Namodenoson capsules orally 25 mg every 12 hours for 36 weeks
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25 mg q12hours x 36 weeks
Other Names:
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Placebo Comparator: Placebo
Matching placebo capsules orally 25 mg every 12 hours for 36 weeks
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Matching capsules q12hours x 36 weeks
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Non-Alcoholic Fatty Liver Disease (NAFLD) activity score (NAS)
Time Frame: 36 weeks
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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)
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36 weeks
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Adverse events (AEs)
Time Frame: 36 weeks
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Incidence of AEs
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36 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Alanine transaminase (ALT) mean
Time Frame: 36 weeks
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Mean percent change from Baseline in serum ALT level
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36 weeks
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Steady-state blood level of namodenoson
Time Frame: 36 weeks
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Plasma trough concentration (ng/mL) of namodenoson taken at pre-dose samples
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36 weeks
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
ALT absolute
Time Frame: 36 weeks
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Absolute change from Baseline in serum ALT
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36 weeks
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ALT threshold
Time Frame: 36 weeks
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Proportion of subjects who achieve ≥17-point reduction from Baseline in serum ALT
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36 weeks
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Weight
Time Frame: 36 weeks
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Change from Baseline in body weight
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36 weeks
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Adiponectin
Time Frame: 36 weeks
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Change from Baseline in serum adiponectin level
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36 weeks
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Released N-terminal pro-peptide of type III collagen neoepitope (Pro-C3)
Time Frame: 36 weeks
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Change from Baseline in Pro-C3
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36 weeks
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Serum Enhanced Liver Fibrosis (ELF) Score
Time Frame: 36 weeks
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Change from Baseline in ELF Score, which is a continuous scale starting at zero, with higher scores indicating more severe disease
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36 weeks
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FibroScan controlled attenuation parameter (CAP)
Time Frame: 36 weeks
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Change from Baseline in CAP
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36 weeks
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FibroScan-AST (FAST) Score
Time Frame: 36 weeks
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Change from Baseline in FAST Score, which is a decimal score from 0 to 1, with higher scores indicating more severe disease
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36 weeks
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Aspartate transaminase (AST)
Time Frame: 36 weeks
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Change from Baseline in serum AST
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36 weeks
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Gamma-glutamyl transferase (GGT)
Time Frame: 36 weeks
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Change from Baseline in serum GGT
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36 weeks
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Fibrosis-4 (Fib-4) Index
Time Frame: 36 weeks
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Change from Baseline in Fib-4 Index
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36 weeks
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NASH resolution
Time Frame: 36 weeks
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Proportion of subjects who achieve histologic NASH resolution as defined by a ballooning score of 0 and an inflammation score of 0-1 without worsening of fibrosis
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36 weeks
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NASH fibrosis improvement
Time Frame: 36 weeks
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Proportion of subjects who achieve histologic NASH improvement by at least 1 point without worsening of NASH
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36 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Michael H Silverman, MD, BioStrategics Consulting Ltd
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 10, 2021
Primary Completion (Estimated)
April 15, 2025
Study Completion (Estimated)
October 15, 2025
Study Registration Dates
First Submitted
January 4, 2021
First Submitted That Met QC Criteria
January 5, 2021
First Posted (Actual)
January 6, 2021
Study Record Updates
Last Update Posted (Estimated)
June 16, 2023
Last Update Submitted That Met QC Criteria
June 15, 2023
Last Verified
June 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CF102-212LD
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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