MAD Study of IA-14069

Exclusion Criteria

• •1. Previous participation in the SAD study (Study IA-14069\_1a).
• •2. Employee of ICON or the Sponsor.
• •3. Use of any investigational drug or device within 30 days (or 5 half-lives if known, whichever is longer) prior to admission.
• •4. Any disease which, in the opinion of the Investigator, poses an unacceptable risk to the subjects or patients.
• •5. Females who are pregnant, lactating, or planning to attempt to become pregnant during this study or within 90 days after the last dosing of study drug.
• •6. Males with female partners who are pregnant, lactating, or planning to attempt to become pregnant during this study or within 90 days after the last dosing of study drug.
• •7. History of relevant drug sensitivity, and/or food allergies, as determined by the Investigator (such as anaphylaxis, hepatotoxicity, or treatment with steroids or epinephrine). Confirmatory circumstances would include treatment with epinephrine or in Emergency Department.
• •8. Allergy or hypersensitivity to active ingredient or excipients.
• •9. Using tobacco or nicotine products within 60 days prior to study drug administration (for subjects in Part 1).
• •10. History within the previous 12 months of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink=12 oz beer, 5 oz wine, and 1.5 oz spirits).
• •11. Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines \[including ecstasy\], phencyclidine, cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants, cotinine \[only exclusionary in Part 1\], and alcohol) at screening or admission to the clinical site.
• •12. Positive screen for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV) antibodies, or HIV-1 and -2 antibodies.
• •13. Donation or loss of more than 450 mL of blood within 60 days prior to study drug administration, or planned donation before 30 days has elapsed after the last dosing of study drug.
• •14. Plasma or platelet donation within 7 days prior to study drug administration through follow-up assessment.
• •15. Significant and/or acute illness within 5 days prior to drug administration that may impact safety assessments, in the opinion of the Investigator.
• •16. Unsuitable veins for blood sampling.
• •17. Chronic use of prescription or nonprescription drugs (including vitamins and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives if known (whichever is longer) prior to the first dosing (except oral or SC MTX, oral glucocorticoid \[prednisone ≤ 10 mg/day or equivalent; this exception is allowed if stable for at least 3 months prior to screening and expected to remain stable throughout the study period\], folic acid and/or folinic acid in Part 2), but considered on a case-by-case basis by the Investigator in consultation with the Medical Monitor and the Sponsor.
• •18. Patients receiving a biologic DMARD, or having received a biologic DMARD within 6 weeks or 5 half-lives if known (whichever is longer) prior to screening (Part 2 only).
• •19. Patients receiving a targeted synthetic DMARD (including apremilast, baricitinib, filgotinib, or tofacitinib), or having received a targeted synthetic DMARD within 6 weeks or 5 half-lives (whichever is longer) prior to screening (Part 2 only).
• •20. Patients receiving a conventional synthetic DMARD (except MTX), or having received a conventional synthetic DMARD within 6 weeks or 5 half-lives (whichever is longer) prior to screening (Part 2 only).
• •21. Strenuous activity, sunbathing, and contact sports within 48 hours (2 days) prior to admission to the clinical site through follow-up assessment.
• •22. Consumption of any nutrients known to modulate CYP enzymes activity (eg, grapefruit or grapefruit juice, pomelo juice, star fruit, or Seville \[blood\] orange products) within 14 days prior to administration of study drug and during the study.
• •23. Unable to comply with the safety monitoring requirements of this clinical study or is considered by the Investigator to be an unsuitable candidate for the study.
• •24. Received a SARS-CoV-2 or any other vaccine within 7 days prior to dosing of study drug.
• •25. Clinically significant hepatic impairment demonstrated by ALT, AST, total bilirubin, gamma-glutamyl transferase (GGT), and prothrombin time as judged by the Investigator at screening and on Day -1.
• •26. Clinically significant renal impairment evidenced by estimated glomerular filtration rate (eGFR) calculated with the Chronic Kidney Disease EpidemiologyCollaboration (CKD-EPI) 2021, and protein in urine as judged by the Investigator at screening and on Day -1.
• •27. Patients with any single parameter of ALT, AST, GGT, or alkaline phosphatase (ALP) exceeding 2.5×ULN or total bilirubin exceeding 1.5×ULN OR any elevation above ULN of more than one parameter of ALT, AST, GGT, ALP, or serum bilirubin at screening and on Day -3.
• •28. Patients with eGFR value calculated with the CKD-EPI 2021 \<60 mL/min/1.73m2 at screening and on Day -3.