ORZILOBEN for Intestinal failure-associated liver disease

Inclusion criteria

• {"criterion_text":"- Persons aged 18 years or older at the time of informed consent."}
• {"criterion_text":"- Agree to use appropriate contraceptive methods based on biological sex and child-bearing potential."}
• {"criterion_text":"- Agree to abstain from sperm or egg donation through 90 or 30 days, respectively, after administration of the last dose of IP."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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%)."}
• {"criterion_text":"- Willingness to maintain current habitual level of physical activity, oral diet, and lifestyle throughout the entire study."}
• {"criterion_text":"- 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

• {"criterion_text":"- Major intestinal surgery within 3 months of screening or planned during the Study Period."}
• {"criterion_text":"- The use of feeding tubes for the administration of study medication."}
• {"criterion_text":"- Clinical, laboratory, imaging, or histopathologic evidence of other causes of acute or chronic liver disease, including autoimmune, viral, metabolic, or alcoholic liver disease."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Presence of hepatic impairment, end-stage liver disease, and/or a model for end-stage liver disease (MELD) score >12."}
• {"criterion_text":"- History of solid organ transplant (except for corneal transplant) or planned transplantation during the Study Period."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Transient elastography read >20.0 kPA within 3 months prior to or during the Screening Period."}
• {"criterion_text":"- Estimated glomerular filtration rate <45 mL/min per 1.73 m2 based on the 2021 CKD-EPI creatinine equation"}

Primary endpoints

• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Safety and tolerability assessed by subject-reported AEs, blood and urine laboratory parameters, vital signs, ECGs, physical examinations, and % subjects discontinuing due to TEAEs."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"PK parameters: AUC0-last, Cmax, Tmax measured on Day 1 and Day 14."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Safety and tolerability assessed by subject-reported AEs, blood and urine laboratory parameters, vital signs, ECGs, physical examinations, and % subjects discontinuing due to TEAEs."}
• {"endpoint_text":"- Part B: Pharmacokinetic parameters will include AUC0-last, Cmax, and Tmax on Day 1 and Day 28.","definition_or_measurement_approach":"PK parameters: AUC0-last, Cmax, Tmax measured on Day 1 and Day 28."}

Belgium

Earliest CTIS Part Ii Submission Date

03-06-2025

Latest Decision Or Authorization Date

18-06-2025

Processing Time Days

15

Number Of Sites

1

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

02-06-2025

Latest Decision Or Authorization Date

18-06-2025

Processing Time Days

16

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

NorthSea Therapeutics B.V.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Netherlands

Contract research organisations

Name

Fortrea Inc.

Responsibilities

sponsorDuties codes: 1,5 (as listed in application)

Name

Almac Clinical Services LLC

Responsibilities

Drug Distribution

Name

Medidata Solutions Inc.

Responsibilities

sponsorDuties codes: 3,7 (as listed in application)

Third parties

• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"codes: 1,5","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient Reimbursement/ Travel Services","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"Drug Distribution","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"codes: 3,7","organisation_type":"Non-Pharmaceutical company"}