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 adult subjects with intestinal failure-associated liver disease (IFALD) receiving parenteral nutrition (PN). The study will be conducted in 2 sequential parts. Up to 36 adult subjects diagnosed with IFALD will be enrolled in the study, of which 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.
Conditions
Intestinal Failure Associated Liver Disease
Recruitment Status
Recruiting
Eligibility Criteria
Key Inclusion Criteria:
Adult persons aged 18 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 ≤2.0 mg/dL in the absence of Gilbert's Syndrome.
Serum albumin ≥3 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.
Intervention
Intervention Type
Intervention Name
Drug
NST-6179 Part A
Drug
NST-6179 Part B
Other
Matched Placebo
Phase
Phase 2
Gender
All
Min Age
18 Years
Max Age
N/A
Download Date
March 18, 2024
Principal Investigator
N/A
Primary Contact Information
mark.puder@childrens.harvard.edu
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Contact
For more information and to contact the study team: