AMBITION: A Phase 2A, Multiple-Center, Single-Blind, Placebo-Controlled Study To Evaluate The Safety and Tolerability of CRV431 Dosed Once Daily in NASH Induced F2 and F3 Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 10
- 主要终点
- Number of Safety and Tolerability Events of CRV431 Versus Placebo.
研究概览
简要总结
This is a randomized, single-blind, placebo-controlled, once daily (QD) dose study of CRV431 in presumed NASH F2/F3 subjects.
详细描述
This is a randomized, single-blind, placebo-controlled, once daily (QD) dose study of CRV431 in presumed NASH F2/F3 subjects. Study will evaluate the safety and tolerability of a once daily 75mg dose and 225mg of CRV431 compared to placebo over 28 days of dosing. Pharmacokinetic parameters of CRV431 and its major metabolites and fraction unbound will also be evaluated. Non-invasive antifibrotic bio-markers will be collected and quantified from presumed NASH F2/F3 subjects dosed with 75mg CRV431 or placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
placebo-controlled
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female between 18 and 75 years of age (inclusive).
- •Capable of giving written informed consent and able to effectively communicate with the investigator and study personnel.
- •Presumed F2/F3 NASH to include: AST >20 IU/L, Pro-C3 >15.5 ng/mL, enhanced liver fibrosis (ELF) score >9.8, and FibroScan >8.5 kPa values.
排除标准
- •Pregnant or breastfeeding or planning to become pregnant during the study period.
- •Known allergy to CRV431, cyclosporine, or any of their inactive ingredients.
- •Positive test for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCVAb) or human immunodeficiency virus antibodies (HIVAb).
- •Well documented causes of chronic liver disease according to standard diagnostic procedures to include any history or presence of decompensated cirrhosis.
- •Subjects with a platelet count <150,000/mL.
- •Subjects with hemoglobin A1c(HbA1c) >9.5%.
- •Weight loss of more than 5% within 3 months prior to randomization.
- •Subjects with a blood pressure to include a systolic pressure >150 or a diastolic pressure >
- •At Screening, an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 mL (calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] method) and/or a Kidney Disease Improving Global Outcomes (KDIGO) category of >G
- •Subjects with a history of organ transplantation. Corneal transplantation will be allowed.
研究组 & 干预措施
Placebo, 75mg
Placebo, softgel capsule, QD, 28 days, fasted conditions
干预措施: Placebo (1 softgel) (Drug)
CRV431 225mg
CRV431, softgel capsule, 225mg, QD, 28 days, fasted conditions
干预措施: CRV431 225mg (Drug)
Placebo, 225mg
CRV431, 3 softgel capsules, 225mg, QD, 28 days, fasted conditions
干预措施: Placebo (3 softgels) (Drug)
CRV431 75mg
CRV431, softgel capsule, 75mg, QD, 28 days, fasted conditions
干预措施: CRV431 75mg (Drug)
结局指标
主要结局
Number of Safety and Tolerability Events of CRV431 Versus Placebo.
时间窗: Time from informed consent to study day 42.
Number of adverse events, serious adverse events, and clinical laboratory abnormalities.
Tmax, of Once Daily (QD) 75mg and 225mg mg Doses of CRV431 is Presumed Non-alcoholic Steatohepatitis F2/F3 Fibrosis Subjects.
时间窗: Day 1 and Day 28
The Tmax value is defined as time to reach maximum whole blood concentration. Each value is a median for the cohort along with the standard deviation presented in hours for Day 1 and Day 28.
AUC 0-last, of Once Daily (QD) 75mg and 225mg mg Doses of CRV431 in Presumed Non-alcoholic Steatohepatitis F2/F3 Fibrosis Subjects.
时间窗: Timepoints for data collection include 0, 2.0 hours, 4.0 hours, 8 hours on both Day 1 and Day 28.
The AUC 0-last value is defined as the area under the whole blood concentration time curve from time 0 to the time of the last measurable concentration. Each value is a geometric mean for the cohort along with the standard deviation for Day 1 and Day 28.
Cmax, of Once Daily (QD) 75mg and 22mg mg Doses of CRV431 is Presumed Non-alcoholic Steatohepatitis F2/F3 Fibrosis Subjects.
时间窗: Day 1 and Day 28
The Cmax value is defined as the maximum whole blood concentration presented as ng/mL. Each value is a geometric mean for the cohort along with the standard deviation for Day 1 and Day 28.
次要结局
未报告次要终点