A Study of NST-6179 in Subjects With Intestinal Failure-Associated Liver Disease (IFALD).
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age16+
SponsorNorthSea Therapeutics B.V.
About this trial
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
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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.
Trial design
Design model
Sequential
Treatments tested in this trial
NST-6179 Part A
DrugOnce daily (QD) oral administration of 800mg (32 mL solution) of NST-6179 for 4 weeks
NST-6179 Part B
DrugOnce daily (QD) oral administration of 1200mg of NST-6179 for 12 weeks
Matched Placebo
Other interventionMatched placebo for administration in Part A or Part B
Treatment groups
36 Participants
are divided into 4 treatment groupsGroup A: Part A-800 mg NST-6179Experimental treatment 1 intervention
Group B: Part A matched NST-6179 placeboExperimental treatment 1 intervention
Group C: Part B- 1200mg NST-6179Experimental treatment 1 intervention
Group D: Part B matched NST-6179 placeboExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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 Weeks2
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 143
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 weeks4
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 weeksSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov