Metabolic dysfunction-associated steatotic liver disease (MASLD), with a specific focus on active liver fibrogenesis (tissue remodelling and the deposition of extracellular matrix/scar tissue Digestive System
Conditions
Interventions
This open-label study spans a maximum 8.5-month period per participant, consisting of two screening visits, up to two dynamic PET imaging sessions, and a final follow-up safety phone call 4–7 days pos
mass dose = 100 µg, administered radioactivity =150 MBq.
[18F]-LNTH-1363S (targeting fibroblast-activation protein)
mass dose = 100 µg, administered radioactivity =150 MBq.
3. Kinetic Sampling: To establish a tracer metabolite-corrected plasma input function and quantify parent tracer-related radioactivity over th
Sponsors
Perceptive Discovery
Eligibility
Sex/Gender
All
Age
23 Years to 75 Years
Inclusion criteria
Inclusion criteria: General Inclusion Criteria (All Participants) 1. Male or female volunteers 2. Agree to follow the contraception requirements of the study 3. Able to give fully informed written consent. Cohort Specific: Patients with MASLD (Cohort A) 1. Volunteers with a diagnosis of MASLD with F3–F4 liver fibrosis based on historic liver biopsy and non-invasive markers: liver stiffness with magnetic resonance elastography (MRE) = 4.3 kPa 2. Alanine aminotransferase (ALT) > upper limit of normal (ULN) and 10% 4. Body Mass Index (BMI) = 25 kg/m2 5. registered with a general practitioner (GP) in the UK Cohort Specific: Healthy Volunteers (Cohort B) 1. Normotensive volunteers deemed healthy on the basis of a clinical history, medical examination, electrocardiogram (ECG), vital signs, and laboratory tests of blood and urine 2. Normal liver stiffness (MRE < 2.5 kPa) 3. BMI in the range 18.5–24.9 kg/m2 4. Liver fat content (MRI-PDFF) < 5%
Exclusion criteria
Exclusion criteria: All volunteers: 1. Positive tests for hepatitis B & C, human immunodeficiency virus (HIV) 2. Severe adverse reaction to any drug 3. History of malignancy or carcinoma in the last 5 years 4. History of liver transplant 5. Presence or history of drug or alcohol abuse 6. Drink more than 14 units of alcohol weekly 7. Smoke more than 10 cigarettes daily or heavy use of e-cigarettes 8. Use of high-dose corticosteroids from 3 months before the first PET scan until the end of the study 9. Participation in other clinical studies of unlicensed medicines, or loss of more than 400 mL of blood, within the 3 months before the first PET scan 10. Clinically relevant abnormal findings at the screening assessment, acute or chronic illness, or clinically relevant abnormal medical history or concurrent medical condition (unless resulting from MASH in Group 1) 11. Possibility that volunteer will not cooperate 12. Pre-menopausal females who are pregnant or lactating, or who are sexually active and not using a reliable method of contraception 13. Unsatisfactory venous access 14. Significant exposure to ionizing radiation (more than 10 mSv) within the previous 12 months 15. Contraindications to arterial cannulation, magnetic resonance imaging (MRI), PET or computed tomography (CT) 16. Objection by General Practitioner (GP).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Quantitative liver uptake and tissue distribution parameters of [68Ga]-CBP8 and [18F]-LNTH-1363S measured using regional total volume of distribution, standardized uptake value , and/or SUV ratio derived from whole-organ 3D regions of interest. at a continuous timecourse during each dynamic PET emission scan (at PET imaging sessions 1 and 2, which are separated by a washout period of at least 7 days and up to 6 months) | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety and tolerability parameters of [68Ga]-CBP8 and [18F]-LNTH-1363S measured using the number and severity of adverse events (AEs), serious adverse events (SAEs), and clinically significant changes in vital signs, ECG parameters, and clinical laboratory safety assessments (haematology, biochemistry) at a continuous timeline from the screening visit, pre- and post-injection during PET imaging sessions 1 and 2, and up to the final safety follow-up phone call (4–7 days post-imaging);Correlation between regional PET radiotracer hepatic uptake and established clinical staging of MASLD disease severity, measured using correlation coefficients (e.g., Pearson/Spearman) mapping quantitative tracer tissue distribution metrics (VT, SUV, and SUVR) against non-invasive clinical fibrosis staging scores and liver enzyme profiles (ALT, AST), at a single timepoint cross-referencing screening clinical data with the quantitative PET parameters captured during imaging sessions 1 and 2 (washout window of 7 days to 6 months between scans) | — |
Countries
England, United Kingdom
Contacts
Public ContactFrans van den Berg
Outcome results
None listed