A Study of NST-6179 in Subjects With Intestinal Failure-Associated Liver Disease (IFALD).
- Conditions
- Intestinal Failure Associated Liver Disease
- Interventions
- Drug: NST-6179 Part BDrug: NST-6179 Part AOther: Matched Placebo
- Registration Number
- NCT05919680
- Lead Sponsor
- NorthSea Therapeutics B.V.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 36
-
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
- liver enzymes (ALP, AST, ALT, or GGT ≥1.5 × upper limit of normal [ULN]) for ≥6 months and/or
- total bilirubin > ULN for ≥6 months.
-
Laboratory parameters consistent with stable liver disease without cirrhosis as defined by:
- ALT and AST <5 × ULN;
- Total bilirubin ≤2.5 mg/dL in the absence of Gilbert's Syndrome.
- Serum albumin ≥2.5 g/dL;
- International normalized ratio (INR) ≤1.3 in the absence of anticoagulant therapy;
- Platelet count ≥120,000/mm3.
Key
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part B- 1200mg NST-6179 NST-6179 Part B up to 12 subjects Part A-800 mg NST-6179 NST-6179 Part A up to 12 subjects Part A matched NST-6179 placebo Matched Placebo up to 6 subjects Part B matched NST-6179 placebo Matched Placebo up to 6 subjects
- Primary Outcome Measures
Name Time Method 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 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)
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 \[GGT\])
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (13)
Mayo Clinic Scottsdale Campus
🇺🇸Scottsdale, Arizona, United States
University of California San Francisco Medical Center
🇺🇸San Francisco, California, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Mayo Clinic Rochester Campus
🇺🇸Rochester, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
The Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Vanderbilt University School of Medicine
🇺🇸Nashville, Tennessee, United States
University of Washington
🇺🇸Seattle, Washington, United States