A Study of NST-6179 in Subjects With Intestinal Failure-Associated Liver Disease (IFALD).
Purpose
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.
Condition
- Intestinal Failure Associated Liver Disease
Eligibility
- Eligible Ages
- Over 16 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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.
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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part A-800 mg NST-6179 |
up to 12 subjects |
|
|
Experimental Part A matched NST-6179 placebo |
up to 6 subjects |
|
|
Experimental Part B- 1200mg NST-6179 |
up to 12 subjects |
|
|
Experimental Part B matched NST-6179 placebo |
up to 6 subjects |
|
Recruiting Locations
Nashville, Tennessee 37232
Dawn Adams
More Details
- Status
- Recruiting
- Sponsor
- NorthSea Therapeutics B.V.