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

Eligibility Criteria

• 1. Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
• 2. Diagnosis of SLE:
• 1. Diagnosis of SLE according to the 2019 EULAR/ACR classification criteria for SLE
• 2. Positive for one or more of: anti-nuclear antibodies (titre ≥ 1:80), anti-dsDNA or anti-Sm performed by the central laboratory at screening. If anti-dsDNA or anti- Sm tests are negative, documented history of test results may be used.
• 3. Active, moderate-severe disease at screening, defined as clinical SLEDAI-2K ≥ 4.
• 4. Intolerance or inadequate response to ≥ 3 available treatments, used for at least 3 months each, such as the following: corticosteroids, anti-malarial drugs, calcineurin inhibitor, methotrexate, azathioprine, leflunomide, mycophenolic acid or its derivatives, cyclophosphamide, belimumab, anifrolumab, or B-cell depleting monoclonal antibodies.
• 3. Diagnosis of IIM:
• 1. Must have "probable" or "definite" diagnosis of PM or DM (excluding IBM and cancer associated myositis) according to the 2017 EULAR/ACR classification criteria for adult myositis.
• 2. Positive for ≥ 1 disease-specific autoantibody performed by the central laboratory at screening.
• 3. MMT-8 score of ≤ 142/150.
• 4. Fulfill at least one of the following criteria of active disease at screening:
• 4. Must be receiving one of the following therapy regimens at screening:
• 1. Oral prednisolone (or equivalent) without additional immunosuppressive medication: Daily dose between 7.5 mg and 20 mg (inclusive) a day for ≥ 2 months prior to signing the ICF. Dose must be stable for ≥ 2 weeks prior to signing the ICF.
• 2. Immunosuppressive treatment with one of the following medications, at a stable dose for ≥ 3 months prior to signing the ICF:
• 5. Blood B-cells above 50 cells/μL at screening.
• 6. IgG levels \> 6g/L at screening.
• 1. Any complications of the disease under study which are judged by the investigator to be life or organ threatening or to require treatments which are not permitted in the protocol, including but not limited to:
• 1. Active severe SLE-driven renal disease.
• 2. History of, or current diagnosis of, catastrophic or severe APS (for example diagnosis of an arterial or central/pulmonary venous clot) within 1 year prior to signing the ICF. Participants with clinically evident APS which is adequately controlled by anticoagulants or aspirin for at least 12 weeks can be recruited into the study.
• 3. Rapidly progressive and/or severe ILD or ILD that requires oxygen supplementation/therapy (of any type).
• 4. Inclusion Body Myositis or cancer associated myositis.
• 2. Active severe, unstable or history of neuropsychiatric SLE including, but not limited to: aseptic meningitis; cerebral vasculitis; myelopathy; demyelination syndromes (ascending, transverse, acute inflammatory demyelinating polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; acute stroke or stroke syndrome; cranial neuropathy; status epilepticus; cerebral ataxia' and mononeuritis multiplex.
• 3. IIM: Pulmonary function tests at screening (or within one month of screening, provided participant confirms no change in respiratory symptoms in the interim) which meet any of the following criteria:
• 1. FVC ≤60% of predicted
• 2. DLCO ≤70% of predicted
• 3. Deterioration in either FVC or DLCO at screening compared to pulmonary function tests performed ≥3 months previously. 4 Infections
• 1. Any clinical suspicion or diagnosis of active infection at screening.
• 2. Opportunistic infection that meets criteria to be an SAE within 3 years.
• 3. Clinically significant chronic infection (eg, osteomyelitis, bronchiectasis) with treatment completed less than 2 months prior to signing the ICF (except for chronic nail infections, which are allowed).
• 4. Any history of infection requiring: