A Microdose Trial Investigating Binding of [68Ga]Ga-DOTA-CYS-ATH001 in Healthy Subjects and Different Patient Groups.

Exclusion Criteria

• •1. Any contraindication for MRI according to a standard checklist used in clinical practice, including claustrophobia, metallic implants or internal electrical devices (e.g., cochlear implant, nerve stimulator, gastric pacemaker, bladder stimulator, cardiac pacemaker, defibrillator, artificial valves in heart, aneurysm clips or coils, etc.), inability to stay in supine position for 90 minutes, and permanent makeup or tattoos which in the Investigator's opinion might jeopardize the participant's safety or interfere with the imaging assessments.
• •2. Having worked as a metal worker or welder.
• •3. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial or influence the results or the participant's ability to participate in the trial.
• •4. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the screening visit.
• •5. Any malignancy within the past 12 months before the screening visit, with the exception of successfully treated basal cell carcinoma of the skin or in situ prostate cancer under active surveillance, with no interventions scheduled during the period of trial participation.
• •6. Any planned major surgery within the duration of the trial participation.
• •7. Participants who are pregnant, currently breastfeeding, or intend to become pregnant during the course of the trial.
• •8. Any positive result at the screening visit for serum hepatitis B surface antigen, hepatitis B or C antibodies and/or human immunodeficiency virus (HIV).
• •9. Any chronic active infection (e.g., HIV, Hepatitis B or C, tuberculosis, etc.).
• •10. Poor peripheral venous access, as judged by the Investigator.
• •11. After 10 minutes of supine rest at the screening visit, any vital signs values outside the following ranges:
• •* Systolic blood pressure: \< 90 or \>165 mmHg, or
• •* Diastolic blood pressure \< 50 or \>100 mmHg, or
• •* Pulse \< 40 or \> 90 bpm
• •12. The participant has a change in body weight ≥5%, 3 months before the screening visit.
• •13. The participant has any laboratory abnormality or condition that, in the Investigator's opinion, could adversely affect the safety of the participant or impair the assessment of trial results.
• •14. Clinically significantly abnormal 12-lead ECG recording result or cardiac symptoms as judged by the Investigator.
• •15. The participant is using any prohibited concomitant medications as described in the protocol, at the discretion of the Investigator.
• •16. Current use of any hormone therapy at doses that may cause metabolic interference as judged by the Investigator. Stable hormonal replacement therapy is allowed.
• •17. Currently participating, or previous participation in another clinical trial within 30 days prior to the screening visit or previous participation in another PET imaging trial within the last 12 months.
• •18. Positive screening result for alcohol at the screening visit (cohorts 1a and 1b only).
• •19. Ongoing or previous alcohol abuse, or long-standing excessive intake of alcohol, as judged by the Investigator.
• •20. Presence or history of drug abuse, as judged by the Investigator.
• •21. History of, or current use of anabolic steroids, as judged by the Investigator.
• •22. Plasma donation within 1 month of screening or blood donation (or corresponding blood loss) during the last 3 months prior to screening.
• •23. The Investigator considers the participant unlikely to comply with trial procedures, restrictions, and requirements.
• •24. The participant is receiving treatment with vitamin E, thiazolidinediones, or glucagon-like peptide-1 receptor agonists unless on a stable dose for 3 months before the screening Visit and is anticipated to maintain the same dosing regimen throughout trial participation.
• •25. Participants with HbA1c ≥48 mmol/mol (6.5%) at screening without a previous diagnosis of T2D must not take part in the study. Participants with a previous diagnosis of T2D are permitted to enter the study if on a stable regimen of antidiabetic therapy for at least 3 months before screening. Participants who are on a stable regimen of antidiabetic therapy for at least 3 months before screening and have HbA1c of ≥ 63 mmol/mol (9%) at screening should be excluded.
• •26. Clinically significant disease, apart from T2D, which in the opinion of the Investigator might interfere with the interpretation of the trial results and/or the safety of the participant, or in any other way unsuitable for participation in this clinical trial.
• •27. The participant has a severe immune-mediated inflammatory disease (IMID) (e.g., rheumatoid arthritis, spondylarthritis disease spectrum, connective tissue disorders, cutaneous inflammatory conditions such as psoriasis, atopic dermatitis, hidradenitis suppurativa, asthma, multiple sclerosis). Participants with inactive IMID or active IMID of mild to moderate severity are permitted to enter the trial.
• •28. Liver stiffness \> 25 kPa by transient elastography or any sign of decompensation. For cohorts 2 and 3, based on the FibroScan® evaluation on the screening visit, and for cohort 5 based on routine elastography performed ≤ 12 months.
• •29. For participants with biopsy-confirmed fibrosis stage F2 or F3, the participant has any of the following during the screening period:
• •* Aspartate aminotransferase (AST) levels \> 5 x the upper limit of normal (ULN).
• •* Alanine aminotransferase (ALT) levels \> 5 x ULN.
• •* Alkaline phosphatase (ALP) ≥ 2 x ULN (cohorts 2 and 3) and ALP ≥ 10 (cohort 5).
• •* Serum creatinine ≥1.5 x ULN or has an estimated glomerular filtration rate (eGFR) \< 45 mL/min/1.73m2 (the revised Lund-Malmö GFR estimating equation will be used).
• •* International normalized ratio (INR) \&gt;1.3.
• •* Total TBL ≥ULN (except for patients with a documented history of Gilbert's syndrome if direct bilirubin is within the normal reference range).
• •* Direct bilirubin ≥ 3 x ULN.
• •* Platelet count \< 60 x 109/L.
• •* Presence or history of ascites, hepatic encephalopathy, or variceal bleeding.
• •* Presence or history of Child-Pugh \> 6 (Class B or C), unless due to therapeutic anticoagulation.
• •* Presence or history of Model for End-Stage Liver disease (MELD) score \>12 (only for cohorts 2-3).
• •Note: It is the Investigator's decision, in consultation with the Sponsor, to allow participants to enter the study who have clinically meaningful rising tendencies in liver chemistries or significantly elevated liver chemistries that do not yet satisfy but could be interpreted as clinically concerning (i.e., AST or ALT \> 4 x ULN) at any visit during the screening period.
• •30. The participant has a change in body weight ≥ 5% after qualifying liver biopsy. Additional criteria for fibrostenotic CD participants (cohort 4)
• •31. MRI findings consistent with only inflammation, i.e., edema, hyperemic intestinal wall, restricted diffusion, mesenteric lymphadenopathy etc.