A Phase 2, Randomized, Double-blind, Placebo-controlled, Dose-finding Study to Evaluate the Efficacy and Safety of ALXN2050 in Adult Participants With Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)

Description

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.

Trial Eligibility

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.

Study Info

Interventions

Locations Recruiting

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