study of alxn2050 in proliferative lupus nephritis (ln) or immunoglobulin a nephropathy (igan)

Conditions: Lupus Nephritis; Immunoglobulin A Nephropathy; IgAN; LN

Summary: this is a phase 2, randomized, double-blind, placebo-controlled, multicenter study of alxn2050 (120 and 180 milligrams \[mg\]) in addition to background therapy consistent with the standard of care in adult participants (≥ 18 to ≤ 75 years of age) with either ln or igan. the study will consist of an up to 6-week screening period, a 26-week blinded initial evaluation period, a 24-week blinded extended treatment period, and an open-label extension (ole) period of up to 2 years. safety will be monitored throughout the study.


Eligibility criteria:
key inclusion criteria: both cohorts * participants on sodium-glucose cotransporter-2 (sglt 2) inhibitors (eg, empagliflozin) must be on a stable dose for ≥ 3 months with no planned change in dose during the blinded treatment periods (through week 50). ln cohort * clinical diagnosis of sle by 2019 american college of rheumatology and european league against rheumatism criteria. * diagnosis of 2018 revised international society of nephrology/renal pathology society classification (active focal or diffuse proliferative ln class iii or iv) confirmed by biopsy obtained ≤ 6 months prior to screening or during screening period. participants may co-exhibit class v disease. participants with de novo or relapsing disease may be eligible. * clinically active ln at screening requiring/receiving immunosuppression induction treatment in the opinion of the investigator. * proteinuria with upcr ≥ 1 g/g based on one 24 hour urine collection during the screening period. igan cohort * established diagnosis of primary igan based on kidney biopsy obtained any time prior to or during the screening period. * mean proteinuria ≥ 1 g/day on 2 complete and valid 24 hour urine collections during the screening period. * for participants with a kidney biopsy performed \> 1 year prior to screening that was used for eligibility: presence of hematuria as defined by a positive result for blood on urine dipstick or ≥ 10 red blood cells (rbcs)/high power field (hpf) microscopy on urine sediment (documented by the local laboratory) during screening period. presence of hematuria documented by the central laboratory may also be acceptable. * compliance with stable and optimal dose of ras inhibitor treatment including maximum allowed or tolerated ace inhibitor and/or arb dose for ≥ 3 months prior to screening with no expected change in dose during the blinded treatment periods (through week 50) (participants with established intolerance to ras inhibitors may be included). * controlled and stable blood pressure (defined as \< 140/90 millimeters of mercury \[mmhg\]) over the past 3 months prior to randomization. key exclusion criteria: both cohorts * egfr ≤ 30 milliliters/minute/1.73 squared meters during screening calculated by chronic kidney disease epidemiology collaboration. * for participants with egfr \< 45 ml/min/1.73 m2 at screening, presence of any of the following in glomeruli on most recent kidney biopsy prior to or during the screening period: 1. ≥ 50% interstitial fibrosis and tubular atrophy 2. ≥ 50% glomerular sclerosis 3. ≥ 50% active crescent formation * concomitant significant renal disease other than ln or igan on the most recent biopsy prior to or during the screening period. * history of solid organ or bone marrow transplant, or planned transplant during the blinded extended treatment period (50 weeks). * splenectomy or functional asplenia. * known or suspected complement deficiency, unless attributable to underlying disease (that is, ln and igan). * bone marrow insufficiency with absolute neutrophil count \< 1.3 × 10\^3/microliter; thrombocytopenia (platelet count \< 50,000/cubic millimeter). ln cohort * participants who have initiated any of the following treatments for the current active ln flare: 1. cyclophosphamide ≤ 6 months prior to screening 2. cnis ≤ 1 months prior to screening 3. a cumulative dose of intravenous (iv) methylprednisolone \> 3 g 4. mycophenolate mofetil \> 2 g/day (or equivalent) for ≥ 8 consecutive weeks prior to screening 5. prednisone or prednisone equivalent ≥ 0.5 mg/kg/day for ≥ 8 consecutive weeks prior to screening * uncontrolled hypertension (systolic blood pressure \> 160 mmhg or diastolic blood pressure \> 110 mmhg) on 2 or more measurements during the screening period. * prior history or clinically active sle-related cerebritis, seizures, stroke, or stroke syndrome requiring treatment or clinically active pericarditis * inability to take or tolerate the standard of care background therapies igan cohort * diagnosis of rapid progressive glomerulonephritis as measured by egfr loss ≥ 30% over a period of 3 months prior to or during the screening period. * secondary etiologies of igan. * prednisone or prednisone equivalent \> 20 mg/day for \> 14 consecutive days or any other systemic immunosuppression for the treatment of igan ≤ 6 months prior to screening * blood pressure of ≥ 140/90 mmhg during the screening period confirmed on 2 measures \> 30 minutes apart.

Keywords: alxn2050 complement factor d complement alternative pathway ln igan