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

Sickle Cell Disease (SCD) Clinical Trial

— STEADFAST  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04053764
• Other study ID #: CSEG101A2203
• Secondary ID: 2018-003608-38
• Status: Completed
• Phase: Phase 2
• Start date: December 10, 2019
• Est. completion date: March 20, 2023

Study information

• Verified date: May 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of the study is 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: March 20, 2023
• Est. primary completion date: March 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of SCD (HbSS and HbSß0-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. Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Kidney Diseases
• Renal Insufficiency, Chronic
• Sickle Cell Disease (SCD)

Intervention

Drug:
• Crizanlizuamb
Crizanlizumab is a concentrate for solution for infusion, i.v. use. Supplied in single use 10 mL vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab
• Standard of Care
HU/HC (hydroxyurea/hydroxycarbamide) and/or ACE (angiotensin-converting enzyme) inhibitors and/or ARBs (angiotensin-receptor blocker)

Locations

Country	Name	City	State
Brazil	Novartis Investigative Site	Porto Alegre
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	São Paulo	SP
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Paris
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Larisa
Ireland	Novartis Investigative Site	Dublin 8
Lebanon	Novartis Investigative Site	Tripoli
Netherlands	Novartis Investigative Site	Amsterdam
Panama	Novartis Investigative Site	Panama
Spain	Novartis Investigative Site	Barcelona	Catalunya
Turkey	Novartis Investigative Site	Adana
Turkey	Novartis Investigative Site	Adana
Turkey	Novartis Investigative Site	Antakya / Hatay
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United States	Our Lady of the Lake Regional Medical Center	Baton Rouge	Louisiana
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	University of Illinois Hospital and Health Sciences System	Chicago	Illinois
United States	East Carolina University BrodySchool of Med. (3)	Greenville	North Carolina
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Univ of Tenn Health Sciences Ctr	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Brazil,  France,  Greece,  Ireland,  Lebanon,  Netherlands,  Panama,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with = 30% decrease in albuminuria (ACR) at 12 months	Percentage of patients with = 30% decrease in ACR at 12 months from baseline.	Baseline to 12 months
Secondary	Change from baseline in albuminuria (ACR) at 3, 6, 9 and 12 months	Change in ACR from baseline to 3, 6, 9, and 12 months of treatment.	Baseline to 3, 6, 9, and 12 months
Secondary	Percentage of patients with = 30% decrease in albuminuria (ACR) at 6 months	Percentage of patients with = 30% decrease in ACR at 6 months from baseline	Baseline to 6 months
Secondary	Percentage of patients with protein to creatinine ratio (PCR) improvement at 12 months	Percentage of patients with PCR improvement at 12 months from baseline. Improvement: = 20% decrease in PCR from baseline	Baseline to 12 months
Secondary	Percentage of patients with a stable protein to creatinine ratio (PCR) at 12 months	Percentage of patients with stable PCR at 12 months from baseline. Stable: within ± 20% change in PCR from baseline	Baseline to 12 months
Secondary	Percentage change in estimated glomerular filtration rate (eGFR)	Percentage change in eGFR from baseline to 3, 6, 9, and 12 months of treatment. The percentage change in eGFR is calculated as the post-baseline eGFR value minus the baseline eGFR divided by the eGFR at baseline.	Baseline to 3, 6, 9, and 12 months
Secondary	Slope of albumin to creatinine ratio (ACR) decline	Slope of ACR decline from baseline to 12 months of treatment based on ACR values at baseline and at 3, 6, 9, and 12 months. The slope of ACR decline will be estimated as a random coefficient in a linear mixed effect model: the model will be fitted to ACR data collected at baseline and at Months 3, 6, 9, and 12.	Baseline to 3, 6, 9, and 12 months
Secondary	Slope of estimated glomerular filtration rate (eGFR) decline	Slope of eGFR decline from baseline to 12 months of treatment based on eGFR values at baseline and at 3, 6, 9, and 12 months. The slope of eGFR decline will be estimated as a random coefficient in a linear mixed effect model: the model will be fitted to eGFR data collected at baseline and at Months 3, 6, 9, and 12.	Baseline to 3, 6, 9, and 12 months
Secondary	Percentage of patients with progression of chronic kidney disease (CKD) at 12 months	Percentage of patients with progression of CKD from baseline to 12 months	Baseline to 12 months
Secondary	Immunogenicity: Levels of anti-drug antibodies (ADA) to crizanlizumab.	Levels of ADA to crizanlizumab at select time points	Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months
Secondary	Annualized rate of visits to emergency room (ER) and hospitalizations	Annualized rate of visits to ER and hospitalizations due to Acute Kidney Injury (AKI) events, Vaso-occlusive crisis (VOCs), or other Sickle Cell Disease (SCD) complications.	Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months
Secondary	Trough serum concentration (Ctrough) of crizanlizumab	Crizanlizumab pre-dose/trough pharmacokinetic samples will be taken at select time points	Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months