A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants With Immunoglobulin A Nephropathy (IgAN)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 579
- 试验地点
- 246
- 主要终点
- Change from Baseline in Proteinuria Based on 24-hour Urine Protein Creatinine Ratio (UPCR) at Week 34
研究概览
简要总结
The primary objective of this study to evaluate efficacy of ravulizumab compared with placebo on proteinuria reduction and change in eGFR in adult participants with IgAN who are at risk of disease progression.
详细描述
The I CAN study will enroll approximately 510 eligible participants with IgAN who are high risk of disease progression. Participants will be on stable concomitant IgAN treatment(s) consistent with standard of care for patients with IgAN for at least 3 months prior to Screening. Approximately 450 participants will be randomized in a 1:1 allocation ratio to receive a weight-based IV infusion of either ravulizumab or placebo. An interim analysis may be conducted at Week 34 to evaluate change in proteinuria and the final analysis will be conducted at Week 106 to evaluate eGFR. In addition, approximately 60 participants with eGFR 20-29 mL/min/1.73m2 will be enrolled in an Advanced Kidney Disease (AdKD) Cohort. After Week 106, all participants have the option to enter an Open-label Ravulizumab Access Period.
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)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documentation of IgAN diagnosis established on kidney biopsy obtained any time prior to or during the Screening Period for participants with eGFR ≥ 30 mL/min/1.73 m^
- •For participants in the AdKD cohorts, eGFR 20 to 29 mL/min/1.73 m2 a kidney biopsy is required within 6 months prior to Screening or during the Screening Period.
- •UPCR ≥ 0.75 g/g or UP ≥1 g/day calculated from the mean of two 24-hour urine during the Screening Period.
- •Estimated GFR ≥ 30 mL/min/1.73 m2 at Screening.
- •Stable and maximum allowed or tolerated RAASI (ACEI and/or ARB) dose for ≥ 3 months prior to Screening with no planned change during Screening through Week
- •Participants who are receiving SGLT2I, DEARA, MRA or ERA must be on a stable and maximum allowed or tolerated dose for ≥ 3 months prior to Screening with no planned change in dose through Week 106.
排除标准
- •Diagnosis of rapid progressive glomerulonephritis as measured by eGFR loss ≥ 50% over a period of 3 months prior to Screening.
- •Secondary IgAN (eg, due to systemic lupus erythematosus (SLE), cirrhosis, or celiac disease; IgAV-N may be eligible).
- •Concomitant clinically significant renal disease other than IgAN.
- •Prior use of immunosuppressive treatment within 3 months of screening.
- •Uncontrolled diabetes mellitus with glycosylated hemoglobin (HbA1c) > 8.5%.
- •Henoch-Schonlein purpura (IgAV) requiring systemic immunosuppressive therapy within 12 months of Screening.
- •History of kidney transplant or planned kidney transplant during the Treatment Period.
- •Splenectomy or functional asplenia.
- •History of Neisseria meningitidis infection.
- •Active systemic bacterial, viral, or fungal infection within 14 days prior to randomization.
研究组 & 干预措施
Placebo IV q8w
Participants will receive a weight-based loading dose on Day 1 followed by weight-based maintenance dosing initiated on Day 15, and then administered q8w.
干预措施: Placebo (Drug)
Ravulizumab IV q8w
Participants will receive a weight-based loading dose on Day 1 followed by weight-based maintenance dosing initiated on Day 15, and then administered every 8 weeks (q8w).
干预措施: Ravulizumab (Drug)
结局指标
主要结局
Change from Baseline in Proteinuria Based on 24-hour Urine Protein Creatinine Ratio (UPCR) at Week 34
时间窗: Baseline, Week 34
Evaluated at interim analysis only
Change from Baseline in Glomerular Filtration Rate (eGFR) at Week 106
时间窗: Baseline, Week 106
Evaluated at final analysis only
次要结局
- Change from Baseline in Proteinuria Based on 24-hour Urine Protein Creatinine Ratio (UPCR) at Weeks 10, 26, 34, 50, and 106(Baseline, Weeks 10, 26, 34, 50, and 106)
- Change From Baseline in eGFR at Weeks 34 and 50(Baseline, Weeks 34 and 50)
- Change From Baseline in Albuminuria at Each Scheduled Visit Up to Week 106(Baseline, at Each Scheduled Visit Up to Week 106)
- Reduction in 24-hour UPCR ≥ 50% From Baseline at Each Scheduled Visit Up to Week 106(Baseline, at Each Scheduled Visit Up to Week 106)
- Number of Participants With Partial Remission at Each Scheduled Visit Up to Week 106(Baseline, at Each Scheduled Visit Up to Week 106)
- Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at Weeks 34, 50, and 106(Baseline, Weeks 34, 50, and 106)
- Annualized eGFR Slope Over 50 Weeks(Baseline, Over 50 Weeks)
- Time to First Composite Kidney Event Up to Week 106(Baseline Up to Week 106)
- Time to Sustained ≥ 30% eGFR Decline Up to Week 106(Baseline Up to Week 106)
- Time to Sustained eGFR Decline ≥ 40% Up to Week 106(Baseline Up to Week 106)
- Use of Alternative IgAN Therapy Up to Week 106(Baseline, Up to Week 106)
- Change from Baseline in Proteinuria Based on 24-hour UPCR at Week 34 with baseline UPCR ≥ 1.5 g/g(Baseline Up to Week 34)
- Change from Baseline in Proteinuria Based on 24-hour UPCR at Week 34 in Participants with Baseline UPCR ≥ 1.5 g/g and Presence of Hematuria at Baseline(Baseline Up to Week 34)
- Change from Baseline in eGFR at Week 106 in Participants with Baseline UPCR ≥ 1.5 g/g(Baseline Up to Week 106)