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NCT05919680PHASE2Recruiting

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

NorthSea Therapeutics B.V.

Start Date

1/15/2024

Completion Date

6/30/2025

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 Criteria

Age Range: 16 years to No maximum

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.

Interventions

DRUG

NST-6179 Part A

DRUG

NST-6179 Part B

OTHER

Matched Placebo

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Conditions

Intestinal Failure Associated Liver Disease

Locations

Mayo Clinic Scottsdale Campus

Scottsdale, Arizona 85259

United States

University of California San Francisco Medical Center

San Francisco, California 94143

United States

MedStar Georgetown University Hospital

Washington D.C., District of Columbia 20007

United States

Emory University School of Medicine

Atlanta, Georgia 30322

United States

The University of Chicago Medical Center

Chicago, Illinois 60637

United States

Boston Children's Hospital

Boston, Massachusetts 02115

United States

Henry Ford Hospital

Detroit, Michigan 48202

United States

Mayo Clinic Rochester Campus

Rochester, Minnesota 55905

United States

Mount Sinai Medical Center

New York, New York 10029

United States

Duke University Medical Center

Durham, North Carolina 27710

United States

The Cleveland Clinic

Cleveland, Ohio 44195

United States

Vanderbilt University School of Medicine

Nashville, Tennessee 37232

United States

University of Washington

Seattle, Washington 98195

United States