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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

NorthSea Therapeutics B.V.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

19 Aug 2025 → ongoing

Decision date (initial)

2025-06-18

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-520202-19-00

ClinicalTrials.gov

NCT05919680

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Pharmacodynamic, Others

- Part A:
• To assess the safety and tolerability of multiple oral doses of NST-6179 for 4 weeks in subjects with IFALD.
• To characterize the PK of NST-6179 in subjects with IFALD.
• To evaluate the effect of colon function on the PK profile of NST-6179 in subjects with IFALD.

- Part B:
• To assess the safety and tolerability of multiple oral doses of NST-6179 for 12 weeks in subjects with IFALD.
• To characterize the PK of NST-6179 in subjects with IFALD.
• To evaluate the effect of colon function on the PK profile of NST-6179 in subjects with IFALD.
• To assess the PD effects of NST-6179 in subjects with IFALD on non-invasive biomarkers of hepatic steatosis, hepatic inflammation, hepatic cholestasis, hepatic fibrosis, lipid metabolism, glucose metabolism, bile acid metabolism, circulating incretins, and intestinal function and injury.
• To evaluate the exposure-response relationship of NST-6179 by assessing the changes in PD biomarkers.

Conditions and MedDRA coding

Subjects with Intestinal Failure-Associated Liver Disease (IFALD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Persons aged 18 years or older at the time of informed consent.
2. Agree to use appropriate contraceptive methods based on biological sex and child-bearing potential.
3. Agree to abstain from sperm or egg donation through 90 or 30 days, respectively, after administration of the last dose of IP.
4. Able to understand the purpose and procedures that are involved in the study and willing to sign a written informed consent form and agrees to comply with the study protocol.
5. Negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) result obtained from test performed according to site standard of care between Day -3 and Day 1.
6. Minimum of 6 months on PN supplementation prior to Visit 1. Any PN prescription is allowed provided the PN is part of the participant’s caloric needs and the participant plans to stay on stable PN therapy throughout the Study.
7. Stable PN regimen for 4 weeks prior to and during the Screening Period. Stable regimen is defined as actual PN usage by volume and energy content and composition consistent with the prescribed regimen (±10%).
8. Willingness to maintain current habitual level of physical activity, oral diet, and lifestyle throughout the entire study.
9. Established clinical diagnosis of IFALD based on a persistent elevation of: a) liver enzymes: ALP and/or AST and/or ALT and/or GGT ≥1.5 × ULN for ≥6 months and/or b) total bilirubin > ULN for ≥6 months

Exclusion criteria 9

1. Major intestinal surgery within 3 months of screening or planned during the Study Period.
2. The use of feeding tubes for the administration of study medication.
3. Clinical, laboratory, imaging, or histopathologic evidence of other causes of acute or chronic liver disease, including autoimmune, viral, metabolic, or alcoholic liver disease.
4. 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).
5. Presence of hepatic impairment, end-stage liver disease, and/or a model for end-stage liver disease (MELD) score >12.
6. History of solid organ transplant (except for corneal transplant) or planned transplantation during the Study Period.
7. Laboratory parameters consistent with unstable or deteriorating liver function as defined by: a. ALP ≥10 × ULN; b. ALT and AST ≥5 × ULN; c. Total bilirubin >2.5 mg/dL in the absence of Gilbert’s Syndrome. i. Gilbert’s Syndrome patients are eligible as long as the direct bilirubin is ≤0.5 mg/dL and ≤20% of the total bilirubin level.
8. Transient elastography read >20.0 kPA within 3 months prior to or during the Screening Period.
9. Estimated glomerular filtration rate <45 mL/min per 1.73 m2 based on the 2021 CKD-EPI creatinine equation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part A: Safety and tolerability assessments will include, but not be limited to, subject-reported adverse events (AEs), blood and urine laboratory parameters, vital sign measurements, electrocardiograms (ECGs), physical examinations, and percentage of subjects discontinuing due to treatment-emergent adverse events (TEAEs).
2. Part A: Pharmacokinetic parameters will include, but not be limited to, area under the concentration-time curve from time 0 to last measurable concentration (AUC0-last), maximum observed concentration (Cmax), and time to reach Cmax (Tmax) on Day 1 and Day 14.
3. Part B: Safety and tolerability assessments will include, but not be limited to, subject-reported AEs, blood and urine laboratory parameters, vital sign measurements, ECGs, physical examinations, and percentage of subjects discontinuing due to TEAEs.
4. Part B: Pharmacokinetic parameters will include AUC0-last, Cmax, and Tmax on Day 1 and Day 28.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

NorthSea Therapeutics B.V.

Sponsor organisation

NorthSea Therapeutics B.V.

Address

Paasheuvelweg 25

City

Amsterdam

Postcode

1105 BP

Country

Netherlands

Scientific contact point

Organisation

NorthSea Therapeutics B.V.

Contact name

Carine Beysen

Public contact point

Organisation

NorthSea Therapeutics B.V.

Contact name

Rob de Ree

Third parties 5

Locations

3 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications