A Study to Characterize the Pharmacokinetics, Pharmacodynamics, and Safety of Anifrolumab in Adult Type I Interferon Test High Systemic Lupus Erythematosus Subject With Active Skin Manifestations
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic; Skin Manifestations
Intervention: Anifrolumab; Placebo
Intervention description: subcutaneous administration every 2 weeks from week 0 to week 50; subcutaneous administration every two weeks from week 0 to week 50
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This study will be conducted to characterize pharmacokinetics, pharmacodynamics, safety, and
      tolerability of anifrolumab given via the subcutaneous (SC) route of administration in adult
      Systemic Lupus Erythematosus (SLE) subjects with a type I Interferon (IFN) test high result
      and active skin manifestations while receiving Standard of Care (SOC) treatment. In addition,
      the efficacy of anifrolumab on SLE skin manifestations will be characterized.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 18 through 70 years

          2. Diagnosis of paediatric or adult SLE for > 24 weeks and fulfilling ≥4 of the 11
             American College of Rheumatology (ACR) classification criteria with at least one
             being:

               -  Positive antinuclear antibody (ANA) or

               -  Elevated anti-dsDNA antibodies or

               -  anti-Smith (anti-Sm) antibodies

          3. Interferon high test result

          4. Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score ≥
             10

          5. Currently receiving at least 1 of the following for treatment of SLE:

             • Oral prednisone or equivalent of ≤40 mg/day for a minimum of 2 weeks prior to
             signing the Informed Consent Form (ICF) and with stable dose for at least 2 weeks
             prior to randomization

             • Any of the following medications for at least 12 weeks prior to signing the ICF, and
             at a stable doses for at least 8 weeks prior to randomization: (i) Azathioprine ≤200
             mg/day (ii) Antimalarials (eg, chloroquine, hydroxychloroquine, quinacrine) (iii)
             Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day (iv) Oral,
             subcutaneous (SC), or intramuscular methotrexate ≤25 mg/week (v) Mizoribine ≤150
             mg/day

          6. Must not have signs of active or latent tuberculosis (TB).

          7. Must not be pregnant or breastfeeding.

        Exclusion Criteria:

          1. Active severe or unstable neuropsychiatric SLE

          2. Active severe SLE-driven renal disease

          3. Any severe herpes infection at any time

          4. Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or HIV infection.

          5. Known history of a primary immunodeficiency (splenectomy, or any underlying condition
             predisposing for infection

          6. Receipt of any investigation product within 4 weeks or 5 half -lives prior to signing
             of the ICF

          7. History of cancer, apart from:

               -  Squamous or basal cell carcinoma of the skin if successfully treated.

               -  Cervical cancer in situ if successfully treated