NCT03261739已完成1 期
An Adaptive Design Study for the Assessment of the Safety, Tolerability, and Pharmacokinetics of RYI-018 After Repeat Dosing in Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 7
- 主要终点
- Clinical evaluation of adverse events
研究概览
简要总结
BRB-018-001 is a multicenter, adaptive design, randomized, parallel group study to evaluate the safety, tolerability, and PK of repeat IV doses of RYI-018 in subjects with NAFLD.
详细描述
BRB-018-001 will be conducted as a multicenter, adaptive design, randomized, parallel group study to evaluate the safety, tolerability, and PK of repeat IV doses of RYI-018 in subjects with NAFLD. Subjects in each cohort shall be randomized to either RYI-018 or placebo as weekly injection for four weeks. The active doses of RYI-018 will be as follows: Cohort 1: 0.6 mg/kg, Cohort 2: 1.2 mg/kg, and Cohort 3: 2.5 mg/kg. Primary endpoints include safety and tolerability. Secondary endpoints include pharmacokinetics and immunogenicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blind, placebo controlled
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult male or females, 18 to 65 years of age (inclusive) at the time of screening.
- •BMI ≥25.0 and ≤40.0 (kg/m2) (inclusive).
- •Liver ultrasound (or transient elastography if approved by medical monitor) which qualitatively shows fatty liver or documented history of NAFLD.
- •Liver fat percentage by MRI of approximately 10% or greater (MRI to be performed only in subjects with documented NAFLD or fatty liver by ultrasound or transient elastography if approved by medical monitor).
- •Type 2 diabetes or prediabetes.
- •Negative urine drug screen/alcohol breath test at screening.
- •Non-smokers as defined by not smoked any tobacco or nicotine-containing products within 3 months prior to screening. No current use of any nicotine containing product.
排除标准
- •Positive serologic testing for HIV, HBsAg, or HCV.
- •Have any known malignancy or history of malignancy, except for basal cell or squamous cell skin cancer that has been treated with no evidence of recurrence for at least 3 months prior to Screening.
- •Have any underlying physical or psychological medical condition that, in the opinion of the Investigator or sponsor, would make it unlikely that the subject will complete the study or is not in the subject's best interest
- •Liver function tests AST or ALT >5 x ULN at screening. One repeat test may be allowed within 7 days at the discretion of the Investigator.
- •Total bilirubin > ULN at screening except in patients with a known history of Gilbert's syndrome.
- •History or presence of alcoholism or drug abuse within the 2 years prior to the first study drug administration.
- •Administration of IP in another trial within 30 Days or 5 times the investigational drug half-life, whichever is longer, prior to the first study drug administration.
- •History of cerebrovascular event acute coronary syndrome within 6 months of screening.
- •Any history of seizures, major depression, suicidality, or unexplained syncope.
- •Subjects with other active (acute or chronic) liver disease other than NAFLD/NASH (e.g., autoimmune liver disease, viral hepatitis, genetic hemochromatosis, Wilson disease, alpha-1-antitrypsin deficiency, alcohol liver disease, drug induced liver disease).
- •Use of prescription or non-prescription weight loss medications, thiazolidinediones, investigational or approved medications for NASH, or antidepressant medications within 90 days of screening.
- •Use of insulin injections within 30 days of screening.
- •History of bariatric surgery or plans for bariatric surgery or an attempt to lose weight during study.
- •Daily alcohol intake >20 g/day for women and >30 g/day for men (on average per day), as per medical history.
- •Subjects with renal dysfunction estimated glomerular filtration rate <60 mL/min/1.73 m
- •HbA1c >9.5% at screening.
- •Pregnant or breastfeeding women.
研究组 & 干预措施
Placebo
Placebo Comparator
vehicle control
干预措施: Placebo (Biological)
RYI- 018
Experimental
The doses of RYI-018 to be evaluated in sequential cohorts will be 0.6 mg/kg, 1.2 mg/kg, and 2.5 mg/kg.
干预措施: RYI-018 (Biological)
结局指标
主要结局
Clinical evaluation of adverse events
时间窗: Continuous through 67 days
Subjects will be assessed for adverse events attributable to RYI-018
次要结局
- Time to peak serum concentration(Week 1, Week 4)
- Peak serum concentration(Week 1, Week 4)
- Area under the serum concentration versus time curve (AUC)(Week 1, Week 4)
- Apparent volume of distribution(Week 1, Week 4)
- Immunogenicity as determined by the concentration of serum anti-RYI-018 antibodies.(Days 8, 15, 22, 29, 36, 67)
研究者
研究点 (7)
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