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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
341
Percentage of Participants Achieving SLE Responder Index (SRI)-4 and Steroid Dose ≤ 10 mg Prednisone Equivalent Once a Day (QD) at Week 24
SLE Responder Index (SRI)-4 is defined as follows with all criteria compared to Baseline: * ≥ 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score * No worsening of the overall condition (\< 0.3 point increase in Physician's Global Assessment \[PhGA\]) * No new British Isles Lupus Assessment Group (BILAG) A or more than 1 new BILAG B disease activity scores (i.e., no organ system changes from baseline B/C/D/E to A and no more than 1 organ system changes from baseline C/D/E to B). A letter score is assigned to each organ system with following indications: A = severe, B = moderate, C = mild, D = inactive with prior history, and E = inactive with no history.
Time frame: Baseline, Week 24
Percentage of Participants Achieving SLE Responder Index (SRI)-4 at Week 24
SLE Responder Index (SRI)-4 is defined as follows with all criteria compared to Baseline: * ≥ 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score * No worsening of the overall condition (\< 0.3 point increase in Physician's Global Assessment \[PhGA\]) * No new British Isles Lupus Assessment Group (BILAG) A or more than 1 new BILAG B disease activity scores (i.e., no organ system changes from baseline B/C/D/E to A and no more than 1 organ system changes from baseline C/D/E to B). A letter score is assigned to each organ system with following indications: A = severe, B = moderate, C = mild, D = inactive with prior history, and E = inactive with no history.
Time frame: Baseline, Week 24
Percentage of Participants Achieving British Isles Lupus Assessment Group (BILAG) Based Combined Lupus Assessment (BICLA) Response at Week 24
BICLA is a composite responder index. Achievement of BICLA response is defined as improvement in all initial A and B BILAG scores, with no more than one new BILAG B score without worsening of the overall condition (no worsening in Physician's Global Assessment \[PhGA\], \< 0.3 point increase) and no worsening of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score.
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Arizona Arthritis & Rheumatology Research, PLLC /ID# 214522
Mesa, Arizona, United States
AZ Arthritis and Rheumotology Research, PLLC /ID# 211329
Phoenix, Arizona, United States
AZ Arthritis and Rheumotology Research, PLLC /ID# 214267
Phoenix, Arizona, United States
Arthritis and Rheumatism Associates /ID# 211411
Jonesboro, Arkansas, United States
Wallace Rheumatic Studies Center, LLC /ID# 211600
Beverly Hills, California, United States
Arthritis & Osteo Medical Ctr /ID# 228235
La Palma, California, United States
Valerius Medical Group & Research Center /ID# 211599
Los Alamitos, California, United States
East Bay Rheumatology Medical /ID# 211638
San Leandro, California, United States
The Lundquist Institute at Harbor-UCLA Medical Center /ID# 213402
Torrance, California, United States
Medvin Clinical Research /ID# 211996
Tujunga, California, United States
...and 150 more locations
Time frame: Baseline, Week 24
Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 24
LLDAS is a state of low disease activity based on Systemic Lupus Erythematosus Disease Activity Index 2000 score (SLEDAI-2K score ≤4 excluding SLEDAI-2K activity in major organ systems), absence of SLE disease activity in major organ systems and new disease activity, Physician's Global Assessment (PhGA ≤1), and concomitant medication usage (steroid dose ≤7.5 mg QD and toleration of immunosuppressive drugs at standard maintenance doses).
Time frame: Baseline, Week 24
Change From Baseline in Daily Prednisone Dose at Week 24
Participants' current use of steroid therapy was assessed at each study visit, and the amount of daily prednisone was documented.
Time frame: From Baseline to Week 24
Number of Flares Per Patient-year by Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLEDAI Flare Index Through Week 24
The SELENA SLEDAI flare index defines mild/moderate or severe SLE flares using the SLEDAI score, definitions of worsening signs and symptoms, treatment changes, and Physician's Global Assessment of Disease Activity.
Time frame: From Baseline to Week 24