Intestinal Failure Associated Liver DiseasePhase 2NCT05919680
A Study of NST-6179 in Subjects With Intestinal Failure-Associated Liver Disease (IFALD).
A Phase 2 study testing NST-6179 Part A and NST-6179 Part B in people with Intestinal Failure Associated Liver Disease, run by NorthSea Therapeutics B.V. at 13 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Intestinal Failure Associated Liver Disease
- What is being tested?
- NST-6179 Part A and NST-6179 Part B
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 13 sitesUnited States
- Study dates
- 15 Jan 2024to 30 Jun 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
- 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:
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- ALT and AST <5 × ULN;
- Total bilirubin ≤2.5 mg/dL in the absence of Gilbert's Syndrome.
- Serum albumin ≥2.5 g/dL;
- International normalized ratio (INR) ≤1.3 in the absence of anticoagulant therapy;
- Platelet count ≥120,000/mm3.
Who cannot join
- 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.
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
United States13 sites, 13 recruiting
- Recruiting
Emory University School of Medicine
Atlanta, Georgia, 30322
Thomas Ziegler, MD
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Mark Puder, MD
- Recruiting
The University of Chicago Medical Center
Chicago, Illinois, 60637
Carol Semrad, MD
- Recruiting
The Cleveland Clinic
Cleveland, Ohio, 44195
Don Kirby, MD
- Recruiting
Henry Ford Hospital
Detroit, Michigan, 48202
Syed-Mohammed Jafri, MD
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Maria Segovia, MD
- Recruiting
Vanderbilt University School of Medicine
Nashville, Tennessee, 37232
Dawn Adams
- Recruiting
Mount Sinai Medical Center
New York, New York, 10029
Kishore Iyer, MD
- Recruiting
Mayo Clinic Rochester Campus
Rochester, Minnesota, 55905
Manpreet Mundi, MD
- Recruiting
University of California San Francisco Medical Center
San Francisco, California, 94143
Kendall Beck, MD
- Recruiting
Mayo Clinic Scottsdale Campus
Scottsdale, Arizona, 85259
John DiBaise, MD
- Recruiting
University of Washington
Seattle, Washington, 98195
Lei Yu, MD
- Not yet recruiting
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Sukanya Subramanian
About this study
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)
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.
- Being tested
- NST-6179 Part A, NST-6179 Part B, Matched Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NST-6179 Part ADrug
Once daily (QD) oral administration of 800mg (32 mL solution) of NST-6179 for 4 weeks
NST-6179 Part BDrug
Once daily (QD) oral administration of 1200mg of NST-6179 for 12 weeks
Matched PlaceboOther
Matched placebo for administration in Part A or Part B
| Study group | Role | What they receive |
|---|---|---|
| Part A-800 mg NST-6179 | Experimental | up to 12 subjects Receives: Drug: NST-6179 Part A |
| Part A matched NST-6179 placebo | Experimental | up to 6 subjects Receives: Other: Matched Placebo |
| Part B- 1200mg NST-6179 | Experimental | up to 12 subjects Receives: Drug: NST-6179 Part B |
| Part B matched NST-6179 placebo | Experimental | up to 6 subjects Receives: Other: Matched Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 14 Weeks
To assess the pharmacokinetics of NST-6179
area under the concentration-time curve from time 0 to last measurable concentration (AUC0-last)
Measured: Day 1 and Day 14
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)
Measured: 12 weeks
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])
Measured: 12 weeks
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])
Measured: 12 weeks
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)
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2023
- Study start15 Jan 2024
- Primary completion30 Jun 2025 (estimated)
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intestinal Failure Associated Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NorthSea Therapeutics B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05919680
- Sponsor's protocol ID
- NST-6179-02
- Status last verified
- Jan 2025
- First submitted
- 16 Mar 2023
- Last updated
- 7 Jan 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05919680
- Acronym / sponsor ID
- NST-6179-02
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- NorthSea Therapeutics B.V.Industry (pharma, biotech, devices)
- Study start
- 15 Jan 2024 (actual)
- Primary completion
- 30 Jun 2025 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 26 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part A-800 mg NST-6179 | Experimental | Drug: NST-6179 Part Aup to 12 subjects |
| Part A matched NST-6179 placebo | Experimental | Other: Matched Placeboup to 6 subjects |
| Part B- 1200mg NST-6179 | Experimental | Drug: NST-6179 Part Bup to 12 subjects |
| Part B matched NST-6179 placebo | Experimental | Other: Matched Placeboup to 6 subjects |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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
- Laboratory parameters consistent with stable liver disease without cirrhosis as defined by:
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NST-6179 Part AOnce daily (QD) oral administration of 800mg (32 mL solution) of NST-6179 for 4 weeks | Drug | Part A-800 mg NST-6179 |
| NST-6179 Part BOnce daily (QD) oral administration of 1200mg of NST-6179 for 12 weeks | Drug | Part B- 1200mg NST-6179 |
| Matched PlaceboMatched placebo for administration in Part A or Part B | Other | Part A matched NST-6179 placebo, Part B matched NST-6179 placebo |
Primary outcome
To assess the safety and tolerability of NST-6179
Time frame: Up to 14 Weeks
Incidences of treatment-emergent adverse events, clinically significant chances in laboratory tests, vital signs and ECGs
To assess the pharmacokinetics of NST-6179
Time frame: Day 1 and Day 14
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
Time frame: 12 weeks
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
Time frame: 12 weeks
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)
Time frame: 12 weeks
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)
Time frame: 12 weeks
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NST-6179 Part A and NST-6179 Part B in people with Intestinal Failure Associated Liver Disease, run by NorthSea Therapeutics B.V. at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michelle Yokley (+31 (0) 35 760 65 05, michelle.yokley@northseatherapeutics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the safety and tolerability of NST-6179 (time frame: Up to 14 Weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2025.