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 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

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.

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	São Paulo	SP
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Paris 15
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 Medic .	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 Participants With = 30% Decrease in Albuminuria (ACR) at 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.	Baseline to 12 months
Secondary	Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months	The effect of SEG101 on clinical disease activity was measured by the change in albuminuria (ACR) between baseline and month 3, baseline and month 6, baseline and month 9, baseline and month 12. A reduction from baseline indicates improvement in patients.	Baseline to 3, 6, 9, and 12 months
Secondary	Percentage of Participants With = 30% Decrease in Albuminuria (ACR) at 6 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 6. A reduction from baseline indicates improvement in patients.	Baseline to 6 months
Secondary	Percentage of Participants With Protein/Creatinine Ratio (PCR) Improvement and Stable PCR at 12 Months	The effect of SEG101 on clinical disease activity was measured by counting patients who had Stable PCR: within ± 20% change from baseline to month 12. PCR improvement: = 20% decrease in PCR from baseline indicates improvement in patients.	Baseline to 12 months
Secondary	Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)	The percentage change in eGFR was calculated as the post-baseline eGFR value minus the baseline eGFR divided by the eGFR at baseline. A reduction from baseline indicates improvement in participants.	Baseline to 3, 6, 9, and 12 months
Secondary	Slope of Albumin to Creatinine Ratio (ACR) Decline	The effect of SEG101 on clinical disease activity was measured by the slope of ACR decline between baseline and Month 12. A reduction from baseline indicates improvement in patients.	Baseline to 12 months
Secondary	Slope of Estimated Glomerular Filtration Rate (eGFR) Decline	The effect of SEG101 on clinical disease activity was measured by the slope of eGFR between baseline and Month 12. The calculation of eGFR is based on the chronic kidney disease epidemiology collaboration (CKD-EPI) (for patients = 18) and Creatinine-based "Bedside Schwartz" (for patients < 18) equations. A reduction in drop rate from baseline indicates improvement in patients.	Baseline to 12 months
Secondary	Percentage of Participants With Progression of Chronic Kidney Disease (CKD) at 12 Months	The effect of SEG101 on clinical disease activity was measured by percentage of participants with CKD progression between baseline and Month 12. A reduction from baseline indicates improvement in participants.; CKD progression is defined as an increase in CKD progression category, a 25% or greater drop in eGFR from baseline or at least 50% increase in ACR for patients with severe (A3) albuminuria and a doubling of albumin levels in patients with moderate (A2) albuminuria.	Baseline to 12 months
Secondary	Shift Table for Chronic Kidney Disease (CKD) Progression	The effect of SEG101 on clinical disease activity was measured by percentage of participants with CKD progression between baseline and Month 12. A reduction from baseline indicates improvement in patients.	Baseline and month 12
Secondary	Immunogenicity: Percentage of Participants With Anti-drug Antibodies (ADA) to Crizanlizumab	The effect of SEG101 on clinical disease activity was measured by percentage of participants shifted to different worst post-baseline categories between baseline and Month 12. An increase in percentage shifting from higher category to lower category indicates improvement in patients.; Baseline is defined as the last non-missing value prior to the first dose.	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	The effect of SEG101 on clinical disease activity was measured by summarizing the annualized rate of visits to ER and hospitalizations between baseline and 1 year 4 months. Annualized rate of hospitalizations and ER visits due to VOC =(Number of ER or hospitalizations reported until End date x 365.25)/(End date-date of first dose of study treatment+1). A reduction from baseline indicates improvement in patients.	Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months
Secondary	Mean Serum Concentration (Ctrough) of Crizanlizumab	The effect of SEG101 on clinical disease activity was measured by checking the concentration of the Drug in serum at different time points.; Crizanlizumab pre-dose/trough pharmacokinetic samples were taken at select time points.	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