Recruiting

NCT Number: NCT05919680

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

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.

Recruiting

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Key information

Conditions

Intestinal Failure Associated Liver Disease

Age range

16 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Mayo Clinic Scottsdale Campus, Scottsdale, Arizona, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

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 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.

Treatment and study plan

NST-6179 Part A

Drug

Once daily (QD) oral administration of 800mg (32 mL solution) of NST-6179 for 4 weeks

NST-6179 Part B

Drug

Once daily (QD) oral administration of 1200mg of NST-6179 for 12 weeks

Matched placebo

Other

Matched placebo for administration in Part A or Part B

Primary outcomes

To assess the safety and tolerability of NST-6179

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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 cholestasis (bilirubin, ALP, GGT)

Time frame: 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])
To assess the pharmacodynamic effects of NST-6179 on hepatic fibrosis (ELF, Pro-C3, FIB-4)

Time frame: 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)

Study contacts

Contact information is provided by the study sponsor or research team.

Michelle Yokley

CONTACT

[email protected]

+31 (0) 35 760 65 05

Sponsors and collaborators

Lead sponsor

NorthSea Therapeutics B.V.

Industry

Registry information

Official study title

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)

Important dates

Study start: 2024
Primary completion: 2025
Study completion: 2025
First posted: Jun 26, 2023
Registry last updated: Jan 7, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.