Resumen

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.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

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.

Criterios de exclusión

Splenectomy or functional asplenia.
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:
≥ 50% interstitial fibrosis and tubular atrophy
≥ 50% glomerular sclerosis
≥ 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).
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:
Cyclophosphamide ≤ 6 months prior to Screening
CNIs ≤ 1 months prior to Screening
A cumulative dose of intravenous (IV) methylprednisolone \> 3 g
Mycophenolate mofetil \> 2 g/day (or equivalent) for ≥ 8 consecutive weeks prior to Screening
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.

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)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

ALXN2050

Placebo

Ubicaciones

Research Site

Research Site

Research Site

Research Site

Patrocinadores