2023-510548-19-00招募中2 期
A Phase 2B Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Namodenoson in the Treatment of Non-Alcoholic Steatohepatitis (NASH)
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 16
- 主要终点
- Proportion of subjects who achieve a ≥2-point improvement in NAS (Week 36, relative to Baseline)
研究概览
简要总结
• 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Double-blind
- 盲法
- Double (Carer, Monitor, Subject, Investigator)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •At least 18 years of age
- •Willing to undergo 2 liver biopsies
- •Willing to comply with scheduled visits, treatment plans, laboratory assessments, and other study-related procedures
- •AST at Screening of ≥20 IU/L
- •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)
- •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 (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)
- •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)
- •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
- •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
排除标准
- •Presence of ascites, hepatic encephalopathy, or other clinical evidence of cirrhosis
- •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
- •Active rheumatoid arthritis treated with small-molecule (including methotrexate) or biologic disease-modifying anti-rheumatic agent concurrently or within 1 year prior to Screening
- •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.
- •More than 7 days of treatment with valproic acid, tamoxifen, amiodarone, or anti-cholinergic agents within 3 months prior to Screening
- •Use of any investigational agent within 4 weeks prior to the Baseline Visit
- •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)
- •Uncontrolled or clinically unstable thyroid disease, in the judgment of the Principal Investigator
- •Concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy
- •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 prior to initiation of study drug
- •Other active acute or chronic liver disease, such as autoimmune hepatitis, hepatitis B, hepatitis C, alcoholic liver disease, or hepatocellular carcinoma
- •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)
- •Pregnant or lactating female
- •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
- •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
- •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 (Appendix 1)
- •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 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
- •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.)
- •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=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
结局指标
主要结局
Proportion of subjects who achieve a ≥2-point improvement in NAS (Week 36, relative to Baseline)
Proportion of subjects who achieve a ≥2-point improvement in NAS (Week 36, relative to Baseline)
次要结局
- The mean PCFB in serum ALT level (Week 36, relative to Baseline)
研究者
Zivit Harpaz
Scientific
Can-Fite Biopharma Ltd.
研究点 (16)
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