NCT05097989终止2 期
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)
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Both Cohorts: Percentage Change in Proteinuria From Baseline at Week 26
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Masking of treatment allocation will be observed at least until Week 50.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
- •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.
排除标准
- •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
- •≥ 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).
- •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).
- •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.
研究组 & 干预措施
LN Cohort: ALXN2050 180 mg
Experimental
Participants diagnosed with LN with an active flare will receive ALXN2050 in addition to standard-of-care background therapy.
干预措施: ALXN2050 (Drug)
LN Cohort: ALXN2050 120 mg
Experimental
Participants diagnosed with LN with an active flare will receive ALXN2050 in addition to standard-of-care background therapy.
干预措施: ALXN2050 (Drug)
LN Cohort: Placebo
Placebo Comparator
Participants diagnosed with LN with an active flare will receive matched placebo in addition to standard-of-care background therapy.
干预措施: Placebo (Drug)
IgAN Cohort: ALXN2050 180 mg
Experimental
Participants diagnosed with IgAN will receive ALXN2050 in addition to standard-of-care background therapy.
干预措施: ALXN2050 (Drug)
IgAN Cohort: ALXN2050 120 mg
Experimental
Participants diagnosed with IgAN will receive ALXN2050 in addition to standard-of-care background therapy.
干预措施: ALXN2050 (Drug)
IgAN Cohort: Placebo
Placebo Comparator
Participants diagnosed with IgAN will receive matched placebo in addition to standard-of-care background therapy.
干预措施: Placebo (Drug)
结局指标
主要结局
Both Cohorts: Percentage Change in Proteinuria From Baseline at Week 26
时间窗: Baseline, Week 26
Proteinuria, the presence of excess proteins in the urine, was assessed using 24-hour urine collections obtained at designated timepoints. A negative change from baseline indicated an improvement in symptoms.
次要结局
- Both Cohorts: Percentage Change in Proteinuria From Baseline at Week 50(Baseline, Week 50)
- Both Cohorts: Percentage of Participants Achieving >30% and >50% Reduction in Proteinuria at Week 26 and Week 50 Compared to Baseline(Week 26 and Week 50)
- Both Cohorts: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 26 and Week 50(Baseline, Week 26 and Week 50)
- LN Cohort: Percentage of Participants Meeting the Criteria for Complete Renal Response at Week 26 and Week 50(Week 26 and Week 50)
- LN Cohort: Percentage of Participants Meeting the Criteria for Partial Renal Response at Week 26 and Week 50(Week 26 and Week 50)
- LN Cohort: Time to the First Occurrence of UPCR ≤0.5 g/g as Measured by a Spot Urine Sample(Up to Week 50)
- LN Cohort: Percentage of Participants Achieving Corticosteroid Taper to 7.5 mg/Day at Weeks 12, 26, and 50(Week 12, Week 26, And Week 50)
- LN Cohort: Percentage of Participants Experiencing a Renal Flare Through Week 50(Baseline Through Week 50)
- LN Cohort: Percentage of Participants Experiencing an Extrarenal SLE Flare Through Week 50(Baseline Through Week 50)
- LN Cohort: Percentage of Participants Meeting the Criteria for Treatment Failure Through Week 50(Baseline through Week 50)
- LN Cohort: Change From Baseline in Serum Albumin at Week 26 and Week 50(Baseline, Week 26 and Week 50)
- LN Cohort: Percentage of Participants Meeting the Criteria for Suboptimal Response Through Week 50(Baseline Through Week 50)
- IgAN Cohort: Percentage of Participants Meeting the Criteria for Partial Remission at Week 26 And Week 50(Week 26 and Week 50)
研究者
研究点 (1)
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