A Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD5492 in Adult Participants With Systemic Lupus Erythematosus or Idiopathic Inflammatory Myopathies or Rheumatoid Arthritis.

This is an open-label, multi-centre Phase I study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD5492 in adult participants with either SLE or IIM or RA. The study consists of 2 parts: Part 1 - Single ascending dose (SAD) Part 1 will be a sequential SAD design in adult participants with SLE. Up to 5 dose levels of AZD5492 are planned to be investigated. Depending on emerging data, up to 4 additional dose levels may be added at the discretion of the Sponsor. The decision to open Part 2 will be made by the Safety Review Committee (SRC) based on the evaluation of all available data including safety, tolerability, PK, and PD from Part 1 and pertinent data arising from other ongoing studies with AZD5492 will also be considered, and the dose levels and dosing strategy for Part 2 will be confirmed. After a screening period of up to 42 days, participants will receive 1 dose of AZD5492 and be followed up for at least 179 days post-dose. Part 2 - Step-up dosing (SUD) Part 2 will be a SUD design in adult participants with SLE, IIM, or RA and consists of: Part 2a (sSUD): 2 dose administrations, 7 days apart (priming dose followed by target dose). Part 2b (dSUD): 3 dose administrations, 7 days apart (2 priming doses followed by a target dose) to further mitigate CRS and ICANS risk. Participants who complete the study may be eligible for re-enrolment and re-treatment according to protocol-defined criteria.