Program to Assess Adverse Events and Change in Disease Activity of Oral Upadacitinib in Adult Participants With Moderate to Severe Systemic Lupus Erythematosus (SELECT-SLE).

Prior treatment

• Class III/IV lupus nephritis that was treated with induction therapy within the 6 months prior to Screening.
• Currently receiving hemodialysis (or other forms of renal replacement therapy)
• Active neuropsychiatric SLE (excluding lupus headache), as defined by the CNS portion of hSLEDAI or BILAG meeting criteria to score A or B, at Screening, or signs or symptoms of neuropsychiatric SLE (excluding lupus headache) within the 6 months prior to Screening.
• A known persistent high-risk antiphospholipid antibody profile (defined as lupus anticoagulant, double positivity, or triple positivity) who are not on anticoagulation or on low-dose aspirin, unless a reason to not take low dose aspirin is documented by the investigator (for anti-cardiolipin and anti--β2 glycoprotein-1, the threshold for positivity is > 40 GPL or MPL. Double positivity means 2 of the following, and triple positivity means three, of the following, are positive: lupus anticoagulant, anticardiolipin IgG or IgM, anti-β2 glycoprotein-1 IgG or IgM); For subjects with a known high risk antiphospholipid antibody profile for whom participation in this clinical trial is considered the most suitable treatment option among treatment alternatives and the risks and benefits have been discussed with the subject, the investigator must document a favorable benefit-risk assessment to justify the subject's inclusion in the study.
• Received IV or IM corticosteroid greater than or equal to a 40 mg prednisone-equivalent bolus within 30 days prior to Baseline; ; or treated with intra-articular, trigger point or tender point, intra-bursa, or intra-tendon sheath corticosteroids in the preceding 30 days prior to Baseline.
• Prior exposure to a systemic or topical JAK inhibitor (including Tyk2 inhibitors), including but not limited to commercial upadacitinib (Rinvoq®), tofacitinib (Xeljanz®), ruxolitinib (Jakafi® or Opzelura®), delgocitinib (Corectim®), baricitinib (Olumiant®), peficitinib (Smyraf®), abrocitinib (Cibinqo®), filgotinib (Jyseleca®), fedratinib (Inrebic), and deucravacitinib (Sotyktu®).

Lab values

• Laboratory values meeting the following criteria within the screening period prior to Baseline: Serum AST > 2.0 × upper limit of normal ULN; Serum ALT > 2.0 × ULN; Serum albumin < 2.0 g/dL (< 20 g/L); WBC < 1,200/μL; ALC < 300/μL;ANC < 1,000/μL; Platelet count < 50,000/μL; Hemoglobin < 9 g/dL; Estimated GFR by simplified 4-variable MDRD formula < 30 mL/min/1.73 m2 ; Urine protein/creatinine ratio ≥2.5 mg protein/mg creatinine (282.5 mg protein/mmol creatinine).

• Adult individuals, 18 years (or acceptable age according to local regulations, whichever is older) to 63 years of age, inclusive, at Screening.
• Clinical diagnosis of SLE at least 24 weeks prior to Screening as defined by the 2019 EULAR/ACR classification criteria for SLE.
• At Screening, must have at least one of the following: ANA+ (titer ≥1:80); anti-dsDNA+; anti-Smith+
• hSLEDAI ≥6, of which ≥4 points are clinical (not based on laboratory criteria), independently reviewed by MCDR at Screening. Clinical hSLEDAI score (not based on laboratory criteria) must be re-confirmed as ≥4 at the Baseline visit. Lupus headache or organic brain syndrome do not count towards the hSLEDAI points required for eligibility but should be documented on the hSLEDAI if present.
• PhGA ≥1 during screening period.
• On stable background treatment for ≥ 60 days prior to Baseline (with the exception of oral corticosteroid [OCS], which must be at a stable dose for ≥14 days prior to Baseline) with: o antimalarial(s) [hydroxychloroquine ≤400 mg daily, chloroquine ≤500 mg daily, quinacrine ≤100 mg daily]; o and/or prednisone (or prednisone-equivalent) (≤20 mg daily); o and/or no more than 1 of the following: azathioprine (≤150 mg daily), 6-mercaptopurine (≤150 mg daily), mycophenolate mofetil (≤2 g daily), mycophenolate sodium ≤1,440 mg/day, leflunomide (≤20 mg daily), cyclosporine, tacrolimus, voclosporin (≤23.7 mg twice daily), methotrexate (≤25 mg weekly), or mizoribine (≤150 mg daily)