The trial will evaluate efficacy, safety and tolerability of ianalumab compared to placebo, given as monthly subcutaneous (s.c.) injection on top of standard-of-care (SoC) treatment in participants with active systemic lupus erythematosus (SLE).
A randomized, double-blind, placebo-controlled multicenter phase 3 study to evaluate efficacy, safety and tolerability of ianalumab on top of standard-of-care therapy in patients with systemic lupus erythematosus (SIRIUS-SLE 2)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
288
Proportion of participants achieving Systemic Lupus Erythematosus Responder Index -4 (SRI-4)
SRI-4 response is defined as: * Systemic Lupus Erythematosus Disease Activity Index - 2000 (SLEDAI-2K) reduction from baseline of ≥ 4 points * No British Isles Lupus Assessment Group-2004 (BILAG-2004) worsening, defined as ≥ 1 new A or ≥ 2 new B items compared to baseline * No worsening in Physician Global Assessment of Disease Activity (PhGA), defined as an increase of ≥ 0.3 from baseline on a 0 to 3 visual analog scale
Time frame: Week 60
Proportion of participants with no moderate or severe BILAG flare
Moderate BILAG flare is defined as 2 or more new BILAG-2004 B items compared to the previous visit; severe BILAG flare is defined as 1 or more new BILAG-2004 A items compared to the previous visit
Time frame: Baseline to Week 60
Proportion of participants maintaining between Week 36 and Week 60 a reduced corticosteroid (CS) dose of predniso(lo)ne ≤ 5 mg/day or ≤ baseline dose, whichever is lower
Maintaining reduced CS dose from Week 36 to Week 60
Time frame: Week 36 to Week 60
Proportion of participants achieving BILAG-based Composite Lupus Assessment (BICLA)
BICLA response is defined as: * Reduction of all baseline BILAG-2004 A to B/C/D and baseline B to C/D and no worsening in other organ systems defined as ≥ 1 new A or ≥ 2 new B items compared to baseline * No worsening from baseline in SLEDAI-2K defined as an increase from baseline of \> 0 points * No worsening in PhGA defined as an increase of ≥ 0.3 from baseline on a 0 to 3 PhGA visual analog scale
Time frame: Week 60
Proportion of participants achieving Lupus Low Disease Activity State (LLDAS)
LLDAS response is defined as: * SLEDAI-2K ≤ 4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) (Golder et al 2019) * No new lupus disease activity compared with the previous assessment, defined as any new SLEDAI-2K component that was not present at the previous assessment * PhGA (scale 0-3) ≤ 1 * Current predniso(lo)ne (or equivalent) dose ≤ 7.5 mg daily * Well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents
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Pinnacle Research Group LLC
Anniston, Alabama, United States
Advanced Medical Research
La Palma, California, United States
University of California LA
Los Angeles, California, United States
Homestead Assoc In Research Inc
Homestead, Florida, United States
IRIS Research and Development
Plantation, Florida, United States
Emory University
Atlanta, Georgia, United States
Willow Rheumatology Wellness
Willowbrook, Illinois, United States
Bluegrass Community Research Inc
Lexington, Kentucky, United States
Accurate Clinical Research
Lake Charles, Louisiana, United States
UMC New Orleans
New Orleans, Louisiana, United States
...and 85 more locations
Time frame: Week 60
Time to first occurrence of SRI-4
Time to first occurrence of SRI-4 from baseline to Week 60
Time frame: Baseline to Week 60
Proportion of participants achieving SRI-4 at Week 60 while maintaining between Week 36 and Week 60 a reduced CS dose of predniso(lo)ne ≤ 5 mg/day or ≤ baseline dose, whichever is lower
Achieving SRI-4 at Week 60 while maintaining between Week 36 and Week 60 a reduced CS dose of predniso(lo)ne ≤ 5 mg/day or ≤ baseline dose, whichever is lower
Time frame: Week 36 to Week 60
Proportion of participants achieving SRI-6
SRI-6 response is defined as: * SLEDAI-2K reduction from baseline of ≥ 6 points * No BILAG-2004 worsening, defined as ≥ 1 new A or ≥ 2 new B items compared to baseline * No worsening in PhGA, defined as an increase of ≥ 0.3 from baseline on a 0 to 3 visual analog scale
Time frame: Week 60
Proportion of participants achieving SF-36 Bodily Pain response
Achieving Short Form 36 (SF-36) Bodily Pain response
Time frame: Week 60
Proportion of participants with Adverse Events (AEs)
To evaluate safety and tolerability of ianalumab s.c. monthly
Time frame: Baseline to Week 60
Incidence and titer of anti-drug (ianalumab) antibodies (ADAs) in serum over time
To evaluate immunogenicity of ianalumab s.c. monthly
Time frame: Baseline to Week 164
Ianalumab concentration in serum during the treatment and follow-up
Concentration of Ianalumab in serum
Time frame: Baseline to Week 164