A Study of NST-6179 in Subjects With Intestinal Failure-Associated Liver Disease (IFALD).

Официальное название

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)

Обзор

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.

Вмешательства

• Препарат NST-6179 Part A
  Once daily (QD) oral administration of 800mg (32 mL solution) of NST-6179 for 4 weeks
• Препарат NST-6179 Part B
  Once daily (QD) oral administration of 1200mg of NST-6179 for 12 weeks
• Другое Matched Placebo
  Matched placebo for administration in Part A or Part B

Первичные конечные точки

• To assess the safety and tolerability of NST-6179 [Срок оценки: Up to 14 Weeks]
• To assess the pharmacokinetics of NST-6179 [Срок оценки: Day 1 and Day 14]
• To assess the pharmacodynamic effects of NST-6179 on hepatic steatosis [Срок оценки: 12 weeks]
• To assess the pharmacodynamic effects of NST-6179 on hepatic inflammation [Срок оценки: 12 weeks]
• To assess the pharmacodynamic effects of NST-6179 on hepatic cholestasis (bilirubin, ALP, GGT) [Срок оценки: 12 weeks]
• To assess the pharmacodynamic effects of NST-6179 on hepatic fibrosis (ELF, Pro-C3, FIB-4) [Срок оценки: 12 weeks]

Критерии участия

Критерии включения

• 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/mm3.

Критерии исключения

• 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 >12.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 13 центров

• Mayo Clinic Scottsdale Campus — Scottsdale
• University of California San Francisco Medical Center — San Francisco
• MedStar Georgetown University Hospital — Washington D.C.
• Emory University School of Medicine — Atlanta
• The University of Chicago Medical Center — Chicago
• Boston Children's Hospital — Boston
• Henry Ford Hospital — Detroit
• Mayo Clinic Rochester Campus — Rochester
• … и ещё 5 центров

Идентификаторы

NCT: NCT05919680 · NST-6179-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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