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

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)

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.

Key Inclusion Criteria:

• 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

  1. liver enzymes (ALP, AST, ALT, or GGT ≥1.5 × upper limit of normal [ULN]) for ≥6 months and/or
  2. total bilirubin > ULN for ≥6 months.

• Laboratory parameters consistent with stable liver disease without cirrhosis as defined by:

  1. ALT and AST <5 × ULN;
  2. Total bilirubin ≤2.5 mg/dL in the absence of Gilbert's Syndrome.
  3. Serum albumin ≥2.5 g/dL;
  4. International normalized ratio (INR) ≤1.3 in the absence of anticoagulant therapy;
  5. Platelet count ≥120,000/mm3.

Key Exclusion Criteria:

• 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.