Study to Characterise Pharmacokinetics (PK), Pharmacodynamics (PD), and Safety of Anifrolumab Administered Subcutaneously (SC) or Intravenously (IV)

This is a multicentre, randomised, phase I open-label study.

The study will comprise of the following:

• Screening period: Up to 30 days
• Two treatment periods
• Part A: Randomised SC vs IV Treatment Period: 5 weeks
• Part B: Optional Extended Treatment Period: Up to 47 weeks
• Safety follow-up period: 12 weeks after the final dose

Part A will include all participants who will be randomised into SC anifrolumab via autoinjector (AI) or IV anifrolumab.

Part B is an optional extended treatment period where participants will receive SC anifrolumab via accessorised prefilled syringe (aPFS).

Inclusion criteria

• Participants who have a diagnosis of adult SLE according to the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2019 criteria for ≥ 24 weeks prior to signing the informed consent form (ICF).
• "Clinical" Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) ≥ 4 points at Screening.
• Antinuclear antibody (ANA)-positive at Screening.
• Must be on stable background standard therapy with oral corticosteroids (OCS), antimalarials, and/or immunosuppressants alone or in combination.

Exclusion criteria

• Active severe or unstable neuropsychiatric SLE.
• Active severe SLE-driven renal disease.
• Known history of primary immunodeficiency, splenectomy, or any underlying condition predisposing to infection, or a positive result for Human Immunodeficiency Virus (HIV) infection confirmed by central laboratory at Screening.
• At Screening, confirmed positive test for hepatitis B serology or positive test for hepatitis C antibody.
• Any severe case of herpes zoster infection at any time prior to Week 0 (Day 1).
• Opportunistic infection requiring hospitalisation or IV antimicrobial treatment within 3 years of randomisation
• History of cancer, apart from:

• Squamous or basal cell carcinoma of the skin treated with documented curative success ≥ 3 months prior to Day 1.
• Cervical cancer in situ treated with apparent curative success ≥ 1 year prior to Day 1.