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

Phase 2RecruitingNCT05919680

NorthSea Therapeutics B.V.36 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Intestinal Failure Associated Liver Disease

Interventions

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

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.

Locations (13)

Mayo Clinic Scottsdale Campus

Scottsdale, Arizona, United States

RECRUITING

University of California San Francisco Medical Center

San Francisco, California, United States

RECRUITING

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

NOT_YET_RECRUITING

Emory University School of Medicine

Atlanta, Georgia, United States

RECRUITING

The University of Chicago Medical Center

Chicago, Illinois, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, United States

RECRUITING

Henry Ford Hospital

Detroit, Michigan, United States

RECRUITING

Mayo Clinic Rochester Campus

Rochester, Minnesota, United States

RECRUITING

Mount Sinai Medical Center

New York, New York, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, United States

RECRUITING

...and 3 more locations

Outcomes

Primary Outcomes

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

Time frame: 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)

Time frame: 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)

Time frame: 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 \[hsCRP\])

Time frame: 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 \[GGT\])

Time frame: 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)

Time frame: 12 weeks

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

Overview

Conditions

Interventions

Eligibility

Locations (13)

Outcomes

Primary Outcomes

Central Contacts