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.

Study Overview

• Status: Recruiting
• Conditions: Intestinal Failure Associated Liver Disease
• Intervention / Treatment: Drug: NST-6179 Part A; Other: Matched Placebo; Drug: NST-6179 Part B

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michelle Yokley; Phone Number: +31 (0) 35 760 65 05; Email: michelle.yokley@northseatherapeutics.com

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic Scottsdale Campus
      • Contact: John DiBaise, MD
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco Medical Center
      • Contact: Kendall Beck, MD
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Not yet recruiting
      • MedStar Georgetown University Hospital
      • Contact: Sukanya Subramanian
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University School of Medicine
      • Contact: Thomas Ziegler, MD
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago Medical Center
      • Contact: Carol Semrad, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Mark Puder, MD
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Hospital
      • Contact: Syed-Mohammed Jafri, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Rochester Campus
      • Contact: Manpreet Mundi, MD
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai Medical Center
      • Contact: Kishore Iyer, MD
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: Maria Segovia, MD
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • The Cleveland Clinic
      • Contact: Don Kirby, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University School of Medicine
      • Contact: Dawn Adams
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • University of Washington
      • Contact: Lei Yu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A-800 mg NST-6179; up to 12 subjects	Drug: NST-6179 Part A; Once daily (QD) oral administration of 800mg (32 mL solution) of NST-6179 for 4 weeks
Experimental: Part A matched NST-6179 placebo; up to 6 subjects	Other: Matched Placebo; Matched placebo for administration in Part A or Part B
Experimental: Part B- 1200mg NST-6179; up to 12 subjects	Drug: NST-6179 Part B; Once daily (QD) oral administration of 1200mg of NST-6179 for 12 weeks
Experimental: Part B matched NST-6179 placebo; up to 6 subjects	Other: Matched Placebo; Matched placebo for administration in Part A or Part B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the safety and tolerability of NST-6179	Incidences of treatment-emergent adverse events, clinically significant chances in laboratory tests, vital signs and ECGs	Up to 14 Weeks
To assess the pharmacokinetics of NST-6179	area under the concentration-time curve from time 0 to last measurable concentration (AUC0-last)	Day 1 and Day 14
To assess the pharmacodynamic effects of NST-6179 on hepatic steatosis	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)	12 weeks
To assess the pharmacodynamic effects of NST-6179 on hepatic inflammation	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])	12 weeks
To assess the pharmacodynamic effects of NST-6179 on hepatic cholestasis (bilirubin, ALP, GGT)	Absolute and relative change from baseline to week 12 in hepatic cholestasis (total bilirubin, direct bilirubin, alkaline phosphatase [ALP], and gamma-glutamyl transferase [GGT])	12 weeks
To assess the pharmacodynamic effects of NST-6179 on hepatic fibrosis (ELF, Pro-C3, FIB-4)	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)	12 weeks

Collaborators and Investigators

• Sponsor: NorthSea Therapeutics B.V.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: June 23, 2023
• First Posted (Actual): June 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 5, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Failure; Liver Diseases
• Other Study ID Numbers: NST-6179-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No