Study Exploring the Effect of Crizanlizumab on Kidney Function in Patients With Chronic Kidney Disease Caused by Sickle Cell Disease
Purpose
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.
Condition
- Sickle Cell Disease (SCD)
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
Exclusion Criteria
- 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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental 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. |
|
|
Active Comparator standard of care |
Patients in the standard of care alone arm will continue to receive their usual standard of care treatment. |
|
More Details
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
Study Contact
Detailed Description
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).