A Study to Investigate the Safety and Efficacy of Elsubrutinib and Upadacitinib Given Alone or in Combination in Participants With Moderately to Severely Active Systemic Lupus Erythematosus (SLE)
Condition: Systemic Lupus Erythematosus (SLE)
MeSH terms: Lupus Erythematosus, Systemic
Intervention: Elsubrutinib; Placebo for elsubrutinib; Upadacitinib; Placebo for upadacitinib
Intervention description: Capsule; Oral; Capsule; Oral; Film-coated tablet; Oral; Film-coated tablet; Oral
Intervention MeSH terms: Upadacitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 341.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Systemic Lupus Erythematosus (SLE); ABBV-105; Upadacitinib; ABBV-599; Elsubrutinib

Summary:

      The main objective of this study was to evaluate the safety and efficacy of elsubrutinib,
      upadacitinib (UPA), and ABBV-599 (elsubrutinib/upadacitinib) High Dose and Low Dose
      combinations vs placebo for the treatment of signs and symptoms of Systemic Lupus
      Erythematosus (SLE) in participants with moderately to severely active SLE and to define
      doses for further development.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant has clinical diagnosis of Systemic Lupus Erythematosus (SLE) at least 24
             weeks prior to Screening, meeting at least 4 of the 11 revised Criteria for
             Classification of SLE according to the 1997 Update of the 1982 American College of
             Rheumatology (ACR) OR meeting at least 4 of the 2012 SLICC classification criteria,
             including at least 1 clinical criterion and 1 immunologic criterion.

          -  At Screening, must have at least one of the following:

               -  antinuclear antibody (ANA)+ (titer ≥ 1:80)

               -  anti-dsDNA+

               -  anti-Smith+

          -  SLEDAI-2K (SLE Disease Activity Index) ≥ 6 despite background therapy as reported and
             independently adjudicated (clinical score ≥ 4, excluding lupus headache and/or organic
             brain syndrome) at Screening:

               -  If 4 points of the required entry points are for arthritis, there must also be a
                  minimum of 3 tender and 3 swollen joints.

               -  If participant has rash and Principal Investigator (PI) considers it to be
                  attributable to SLE, participant must consent to skin photograph collection for
                  adjudication.

               -  Score must be re-confirmed at the Baseline visit.

          -  Physician's Global Assessment (PhGA) ≥ 1 during screening period.

          -  Must be on background treatment, stable for 30 days prior to Baseline and throughout
             the study with antimalarial(s), prednisone (or prednisone equivalent) (≤ 20 mg),
             azathioprine (≤ 150 mg), mycophenolate (<2 g), leflunomide (≤ 20 mg), cyclosporine,
             tacrolimus, and/or methotrexate (MTX) (≤ 20 mg).

               -  No combinations of the above with immunomodulators other than prednisone (or
                  equivalents) and antimalarials.

        Exclusion Criteria:

        - Participant using intravenous (IV) or intramuscular (IM) corticosteroids greater than or
        equal to a 40 mg prednisone-equivalent bolus within 30 days of planned randomization.