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

NCT05919680 · tracked via the Priya Life Science USA tracker

Sponsor

NorthSea Therapeutics B.V

Phase

Phase 2

Started

2024-01-15

Last updated

2025-01-07

Condition(s) studied

Intestinal Failure Associated Liver Disease

Investigational drug(s) / intervention(s)

NST-6179 Part ANST-6179 Part BMatched Placebo

NST-6179 Part A: Once daily (QD) oral administration of 800mg (32 mL solution) of NST-6179 for 4 weeks

NST-6179 Part B: Once daily (QD) oral administration of 1200mg of NST-6179 for 12 weeks

Matched Placebo: Matched placebo for administration in Part A or Part B

Study summary

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.

Eligibility

Sex

ALL

Min age

16 Years

Max age

—

Healthy volunteers

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.

Primary outcome measure(s)

To assess the safety and tolerability of NST-6179 — 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 — 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 — 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 — 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 cholestasis (bilirubin, ALP, GGT) — 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 \[GGT\])
To assess the pharmacodynamic effects of NST-6179 on hepatic fibrosis (ELF, Pro-C3, FIB-4) — 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)

Trial sites (13)

Facility	City	Region	Status
Mayo Clinic Scottsdale Campus	Scottsdale	Arizona	Recruiting
University of California San Francisco Medical Center	San Francisco	California	Recruiting
MedStar Georgetown University Hospital	Washington D.C.	District of Columbia	Not Yet Recruiting
Emory University School of Medicine	Atlanta	Georgia	Recruiting
The University of Chicago Medical Center	Chicago	Illinois	Recruiting
Boston Children's Hospital	Boston	Massachusetts	Recruiting
Henry Ford Hospital	Detroit	Michigan	Recruiting
Mayo Clinic Rochester Campus	Rochester	Minnesota	Recruiting
Mount Sinai Medical Center	New York	New York	Recruiting
Duke University Medical Center	Durham	North Carolina	Recruiting
The Cleveland Clinic	Cleveland	Ohio	Recruiting
Vanderbilt University School of Medicine	Nashville	Tennessee	Recruiting
University of Washington	Seattle	Washington	Recruiting

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05919680 on ClinicalTrials.gov ↗ ← All trials in the USA