A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orziloben (NST-6179) in Subjects With Intestinal Failure-Associated Liver Disease (IFALD)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 36
- 试验地点
- 13
- 主要终点
- To assess the safety and tolerability of NST-6179
研究概览
简要总结
This is a phase 2a, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NST-6179 in subjects with intestinal failure-associated liver disease (IFALD) receiving parenteral nutrition (PN).
The study will be conducted in 2 sequential parts. Up to 36 subjects diagnosed with IFALD will be enrolled in the study, of which up to 18 subjects will be enrolled in each of the 2 parts and randomized (2:1) to receive NST-6179 (N=12/part) or matched placebo (N=6/part). Subjects in Part A will receive once daily (QD) oral administration of 800 mg (32 mL solution) NST-6179 or placebo for 4 weeks. The NST-6179 dose for Part B is planned to be 1200 mg QD for 12 weeks. Actual dose, however, will be determined during the safety review meeting.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult persons aged 16 years or older at the time of informed consent.
- •Minimum of 6 months on Parenteral supplementation.
- •Established clinical diagnosis of IFALD based on a persistent elevation of
- •liver enzymes (ALP, AST, ALT, or GGT ≥1.5 × upper limit of normal [ULN]) for ≥6 months and/or
- •total bilirubin > ULN for ≥6 months.
- •Laboratory parameters consistent with stable liver disease without cirrhosis as defined by:
- •ALT and AST <5 × ULN;
- •Total bilirubin ≤2.5 mg/dL in the absence of Gilbert's Syndrome.
- •Serum albumin ≥2.5 g/dL;
- •International normalized ratio (INR) ≤1.3 in the absence of anticoagulant therapy;
- •Platelet count ≥120,000/mm
排除标准
- •Clinical, laboratory, imaging, or histopathologic evidence of other causes of acute or chronic liver disease, including autoimmune, viral, metabolic, or alcoholic liver disease.
- •Clinical evidence of compensated or decompensated hepatic cirrhosis as assessed by historical liver histology, ultrasound-based and/or signs and symptoms of hepatic decompensation (including, but not limited to, jaundice, ascites, variceal hemorrhage, and/or hepatic encephalopathy).
- •Presence of hepatic impairment, end-stage liver disease, and/or a model for end-stage liver disease (MELD) score >
- •Transient elastography read >20.0 kPA within 3 months prior to or during the Screening Period.
- •Estimated glomerular filtration rate <45 mL/min based on the 2021 CKD-EPI creatinine equation.
- •Poor nutritional status defined as body mass index (BMI) <17 kg/m2.
研究组 & 干预措施
Part B matched NST-6179 placebo
up to 6 subjects
干预措施: Matched Placebo (Other)
Part A-800 mg NST-6179
up to 12 subjects
干预措施: NST-6179 Part A (Drug)
Part A matched NST-6179 placebo
up to 6 subjects
干预措施: Matched Placebo (Other)
Part B- 1200mg NST-6179
up to 12 subjects
干预措施: NST-6179 Part B (Drug)
结局指标
主要结局
To assess the safety and tolerability of NST-6179
时间窗: Up to 14 Weeks
Incidences of treatment-emergent adverse events, clinically significant chances in laboratory tests, vital signs and ECGs
To assess the pharmacokinetics of NST-6179
时间窗: Day 1 and Day 14
area under the concentration-time curve from time 0 to last measurable concentration (AUC0-last)
To assess the pharmacodynamic effects of NST-6179 on hepatic steatosis
时间窗: 12 weeks
Relative change from baseline to week 12 in biomarkers for hepatic steatosis as measured by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) and controlled attenuation parameter (CAP)
To assess the pharmacodynamic effects of NST-6179 on hepatic inflammation
时间窗: 12 weeks
Absolute and relative change from baseline to week 12 in hepatic inflammation (aspartate transaminase \[AST\], alanine transaminase \[ALT\], and high sensitivity C-reactive protein \[hsCRP\])
To assess the pharmacodynamic effects of NST-6179 on hepatic fibrosis (ELF, Pro-C3, FIB-4)
时间窗: 12 weeks
Absolute and relative change from baseline to week 12 in hepatic fibrosis as measured non-invasively by FibroScan VCTE kPa, enhanced liver fibrosis (ELF) score (and individual components), propeptide of type III collagen (PRO-C3), and fibrosis-4 (FIB-4)
To assess the pharmacodynamic effects of NST-6179 on hepatic cholestasis (bilirubin, ALP, GGT)
时间窗: 12 weeks
Absolute and relative change from baseline to week 12 in hepatic cholestasis (total bilirubin, direct bilirubin, alkaline phosphatase \[ALP\], and gamma-glutamyl transferase \[GGT\])
次要结局
未报告次要终点