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)
NorthSea Therapeutics B.V.
36 participants
Jan 15, 2024
INTERVENTIONAL
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
Inclusion Criteria11
- 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.
Exclusion Criteria6
- 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.
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Interventions
Once daily (QD) oral administration of 800mg (32 mL solution) of NST-6179 for 4 weeks
Once daily (QD) oral administration of 1200mg of NST-6179 for 12 weeks
Matched placebo for administration in Part A or Part B
Locations(13)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05919680