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A Study of NST-6179 in Adult Subjects With Intestinal Failure-Associated Liver Disease (IFALD).

Primary Purpose

Intestinal Failure Associated Liver Disease

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
NST-6179 Part A
NST-6179 Part B
Matched Placebo
Sponsored by
NorthSea Therapeutics B.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intestinal Failure Associated Liver Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Part A-800 mg NST-6179

    Part A matched NST-6179 placebo

    Part B- 1200mg NST-6179

    Part B matched NST-6179 placebo

    Arm Description

    up to 12 subjects

    up to 6 subjects

    up to 12 subjects

    up to 6 subjects

    Outcomes

    Primary Outcome Measures

    To assess the safety and tolerability of NST-6179
    Incidences of treatment-emergent adverse events, clinically significant chances in laboratory tests, vital signs and ECGs
    To assess the pharmacokinetics of NST-6179
    area under the concentration-time curve from time 0 to last measurable concentration (AUC0-last)
    To assess the pharmacodynamic effects of NST-6179 on hepatic steatosis
    Relative change from baseline to week 12 in biomarkers for hepatic steatosis as measured by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) and controlled attenuation parameter (CAP)
    To assess the pharmacodynamic effects of NST-6179 on hepatic inflammation
    Absolute and relative change from baseline to week 12 in hepatic inflammation (aspartate transaminase [AST], alanine transaminase [ALT], and high sensitivity C-reactive protein [hsCRP])
    To assess the pharmacodynamic effects of NST-6179 on hepatic cholestasis (bilirubin, ALP, GGT)
    Absolute and relative change from baseline to week 12 in hepatic cholestasis (total bilirubin, direct bilirubin, alkaline phosphatase [ALP], and gamma-glutamyl transferase [GGT])
    To assess the pharmacodynamic effects of NST-6179 on hepatic fibrosis (ELF, Pro-C3, FIB-4)
    Absolute and relative change from baseline to week 12 in hepatic fibrosis as measured non-invasively by FibroScan VCTE kPa, enhanced liver fibrosis (ELF) score (and individual components), propeptide of type III collagen (PRO-C3), and fibrosis-4 (FIB-4)

    Secondary Outcome Measures

    Full Information

    First Posted
    March 16, 2023
    Last Updated
    June 23, 2023
    Sponsor
    NorthSea Therapeutics B.V.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05919680
    Brief Title
    A Study of NST-6179 in Adult 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 NST-6179 in Adult Subjects With Intestinal Failure-Associated Liver Disease (IFALD)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 30, 2023 (Anticipated)
    Primary Completion Date
    June 30, 2025 (Anticipated)
    Study Completion Date
    June 30, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    NorthSea Therapeutics B.V.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    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 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Intestinal Failure Associated Liver Disease

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Sequential Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    36 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Part A-800 mg NST-6179
    Arm Type
    Experimental
    Arm Description
    up to 12 subjects
    Arm Title
    Part A matched NST-6179 placebo
    Arm Type
    Experimental
    Arm Description
    up to 6 subjects
    Arm Title
    Part B- 1200mg NST-6179
    Arm Type
    Experimental
    Arm Description
    up to 12 subjects
    Arm Title
    Part B matched NST-6179 placebo
    Arm Type
    Experimental
    Arm Description
    up to 6 subjects
    Intervention Type
    Drug
    Intervention Name(s)
    NST-6179 Part A
    Intervention Description
    Once daily (QD) oral administration of 800mg (32 mL solution) of NST-6179 for 4 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    NST-6179 Part B
    Intervention Description
    Once daily (QD) oral administration of 1200mg of NST-6179 for 12 weeks
    Intervention Type
    Other
    Intervention Name(s)
    Matched Placebo
    Intervention Description
    Matched placebo for administration in Part A or Part B
    Primary Outcome Measure Information:
    Title
    To assess the safety and tolerability of NST-6179
    Description
    Incidences of treatment-emergent adverse events, clinically significant chances in laboratory tests, vital signs and ECGs
    Time Frame
    Up to 14 Weeks
    Title
    To assess the pharmacokinetics of NST-6179
    Description
    area under the concentration-time curve from time 0 to last measurable concentration (AUC0-last)
    Time Frame
    Day 1 and Day 14
    Title
    To assess the pharmacodynamic effects of NST-6179 on hepatic steatosis
    Description
    Relative change from baseline to week 12 in biomarkers for hepatic steatosis as measured by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) and controlled attenuation parameter (CAP)
    Time Frame
    12 weeks
    Title
    To assess the pharmacodynamic effects of NST-6179 on hepatic inflammation
    Description
    Absolute and relative change from baseline to week 12 in hepatic inflammation (aspartate transaminase [AST], alanine transaminase [ALT], and high sensitivity C-reactive protein [hsCRP])
    Time Frame
    12 weeks
    Title
    To assess the pharmacodynamic effects of NST-6179 on hepatic cholestasis (bilirubin, ALP, GGT)
    Description
    Absolute and relative change from baseline to week 12 in hepatic cholestasis (total bilirubin, direct bilirubin, alkaline phosphatase [ALP], and gamma-glutamyl transferase [GGT])
    Time Frame
    12 weeks
    Title
    To assess the pharmacodynamic effects of NST-6179 on hepatic fibrosis (ELF, Pro-C3, FIB-4)
    Description
    Absolute and relative change from baseline to week 12 in hepatic fibrosis as measured non-invasively by FibroScan VCTE kPa, enhanced liver fibrosis (ELF) score (and individual components), propeptide of type III collagen (PRO-C3), and fibrosis-4 (FIB-4)
    Time Frame
    12 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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.

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    A Study of NST-6179 in Adult Subjects With Intestinal Failure-Associated Liver Disease (IFALD).

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