Study Exploring the Effect of Crizanlizumab on Kidney Function in Patients With Chronic Kidney Disease Caused by Sickle Cell Disease (STEADFAST)

Novartis

Status and phase: Completed; Phase 2

Conditions: Sickle Cell Disease (SCD)

Treatments: Drug: Standard of Care; Drug: Crizanlizuamb

Study type: Interventional

Funder types: Industry

Identifiers

NCT04053764

2018-003608-38 (EudraCT Number)

CSEG101A2203

Details and patient eligibility

About

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.

Full 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).

Enrollment: 58 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

58 participants in 2 patient groups

crizanlizumab + standard of care

Experimental group

Description:

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.

Treatment:

Drug: Crizanlizuamb

Drug: Standard of Care

standard of care

Active Comparator group

Description:

Patients in the standard of care alone arm will continue to receive their usual standard of care treatment.

Treatment:

Drug: Standard of Care