Clinical trial NCT05919680: A Study of NST-6179 in Subjects With Intestinal Failure-Associated Liver Disease (IFALD).
Official 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Intestinal Failure Associated Liver Disease
Lead sponsor: NorthSea Therapeutics B.V.
Sponsor class: INDUSTRY
First posted: 2023-06-26
Enrollment: 36
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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 criteria: 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

  1. liver enzymes (ALP, AST, ALT, or GGT ≥1.5 × upper limit of normal \[ULN\]) for ≥6 months and/or
  2. total bilirubin \> ULN for ≥6 months.
* Laboratory parameters consistent with stable liver disease without cirrhosis as defined by:

  1. ALT and AST \<5 × ULN;
  2. Total bilirubin ≤2.5 mg/dL in the absence of Gilbert's Syndrome.
  3. Serum albumin ≥2.5 g/dL;
  4. International normalized ratio (INR) ≤1.3 in the absence of anticoagulant therapy;
  5. 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.

Primary outcomes:
measure: To assess the safety and tolerability of NST-6179
timeFrame: Up to 14 Weeks
measure: To assess the pharmacokinetics of NST-6179
timeFrame: Day 1 and Day 14
measure: To assess the pharmacodynamic effects of NST-6179 on hepatic steatosis
timeFrame: 12 weeks
measure: To assess the pharmacodynamic effects of NST-6179 on hepatic inflammation
timeFrame: 12 weeks
measure: To assess the pharmacodynamic effects of NST-6179 on hepatic cholestasis (bilirubin, ALP, GGT)
timeFrame: 12 weeks
measure: To assess the pharmacodynamic effects of NST-6179 on hepatic fibrosis (ELF, Pro-C3, FIB-4)
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale Campus
state: Arizona
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester Campus
state: Minnesota
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University School of Medicine
state: Tennessee
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
References: