A Phase II, Multicenter, Randomized, Open Label Two Arm Study Evaluating the Effect of Crizanlizumab + Standard of Care and Standard of Care Alone on Renal Function in Sickle Cell Disease Patients ≥ 16 Years With Chronic Kidney Disease Due to Sickle Cell Nephropathy (STEADFAST)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 7
- 主要终点
- Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 12 Months
研究概览
简要总结
The goal of the study was to evaluate descriptively the effect of crizanlizumab + standard of care and standard of care alone on renal function in sickle cell disease patients ≥ 16 years with chronic kidney disease due to sickle cell nephropathy.
详细描述
Approximately 50 patients were to be randomized 1:1 to receive either crizanlizumab (5 mg/kg) + standard of care or standard of care alone. Patients were stratified at randomization based on chronic kidney disease (CKD) risk category (moderate risk or high/very high risk) and hydroxyurea/hydroxycarbamide (HU/HC) prescription (Yes/No). The CKD risk categories used for stratification were based on both Estimated glomerular filtration rate(eGFR) and albuminuria assessed by Albumin/creatinine ratio (ACR).
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
- None
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
- •Confirmed diagnosis of SCD (HbSS and HbSβ0-thal SCD genotypes are eligible)
- •Patients with eGFR ≥ 45 to ≤ 140 mL/min/1.73 m2 based on CKD EPI formula (patients ≥ 18) or the Creatinine-based "Bedside Schwartz" equation (patients < 18)
- •Patients with ACR of ≥ 100 to < 2000 mg/g (taken as an average of the three screening ACR values to determine eligibility)
- •Receiving at least 1 standard of care drug(s) for SCD-related CKD: If receiving HU/HC, the patient must have been receiving HU/HC for at least 6 months and on a stable dose for 3 months, and/or an ACE inhibitor and/or ARB for 3 months and on a stable dose for those 3 months.
- •Hb ≥ 4.0 g/dL, absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L, and platelet count ≥ 75 x 10^9/L
- •Adequate hepatic function as defined by:
- •Alanine aminotransferase (ALT) < 3.0 x upper limit of normal (ULN)
- •Direct (conjugated) bilirubin ≤ 3.0 x ULN
- •Written informed consent (or assent/ parental consent for minor subjects) prior to any screening procedures
排除标准
- •History of stem cell transplant
- •Patients with evidence of AKI within 3 months of study entry (can decrease interval to within 6 weeks of study entry only if renal function has returned to pre-AKI values prior to study entry)
- •Blood pressure > 140/90 mmHg despite treatment
- •Patients undergoing renal replacement therapy (ie. hemodialysis, peritoneal dialysis, hemofiltration and kidney transplantation)
- •Received blood products within 30 days of Week 1 Day 1
- •Participating in a chronic transfusion program
- •History of kidney transplant
- •Patients with hypoalbuminemia
- •Body mass index of ≥ 35
- •Currently receiving or received voxelotor within 6 months of screening
- •Patient has received crizanlizumab and/or other selectin inhibitor or plans to receive it during the duration of the study.
研究组 & 干预措施
crizanlizumab + standard of care
5 mg/kg by intravenous (i.v.) infusion at Week 1 Day 1, Week 3 Day 1 and Day 1 of every 4-week cycle until Week 51 in addition to their usual standard of care treatment.
干预措施: Crizanlizuamb (Drug)
crizanlizumab + standard of care
5 mg/kg by intravenous (i.v.) infusion at Week 1 Day 1, Week 3 Day 1 and Day 1 of every 4-week cycle until Week 51 in addition to their usual standard of care treatment.
干预措施: Standard of Care (Drug)
standard of care
Patients in the standard of care alone arm will continue to receive their usual standard of care treatment.
干预措施: Standard of Care (Drug)
结局指标
主要结局
Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 12 Months
时间窗: Baseline to 12 months
The effect of SEG101 on clinical disease activity was measured by at least 30% decrease in Albumin to Creatinine Ratio (ACR) from baseline to month 12. A reduction from baseline indicates improvement in patients.
次要结局
- Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 6 Months(Baseline to 6 months)
- Percentage of Participants With Protein/Creatinine Ratio (PCR) Improvement and Stable PCR at 12 Months(Baseline to 12 months)
- Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)(Baseline to 3, 6, 9, and 12 months)
- Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months(Baseline to 3, 6, 9, and 12 months)
- Slope of Albumin to Creatinine Ratio (ACR) Decline(Baseline to 12 months)
- Slope of Estimated Glomerular Filtration Rate (eGFR) Decline(Baseline to 12 months)
- Percentage of Participants With Progression of Chronic Kidney Disease (CKD) at 12 Months(Baseline to 12 months)
- Shift Table for Chronic Kidney Disease (CKD) Progression(Baseline and month 12)
- Immunogenicity: Percentage of Participants With Anti-drug Antibodies (ADA) to Crizanlizumab(Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months)
- Annualized Rate of Visits to Emergency Room (ER) and Hospitalizations(Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months)
- Mean Serum Concentration (Ctrough) of Crizanlizumab(Pre-dose and 336 hours post-dose on Week 3 Day 1; pre-dose and 672 hours post dose on Week 11 Day 1, Week 23 Day 1 and Week 39 Day 1; and 672 hours post dose on Week 53 Day 1)