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

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)

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease (SCD)
• Intervention / Treatment: Drug: Crizanlizuamb; Drug: Standard of Care

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Porto Alegre, Brazil, 90035-003
    • Novartis Investigative Site
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20.211-030
      • Novartis Investigative Site
  • SP
    • Sao Paulo, SP, Brazil, 08270-070
      • Novartis Investigative Site
    • São Paulo, SP, Brazil, 01232-010
      • Novartis Investigative Site
• France
  • Creteil, France, 94000
    • Novartis Investigative Site
  • Paris, France, 75015
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 115 27
    • Novartis Investigative Site
  • Larisa, Greece, 41221
    • Novartis Investigative Site
• Ireland
  • Dublin 8, Ireland
    • Novartis Investigative Site
• Lebanon
  • Tripoli, Lebanon, 1434
    • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Novartis Investigative Site
• Panama
  • Panama, Panama, 0801
    • Novartis Investigative Site
• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
• Turkey
  • Adana, Turkey, 01330
    • Novartis Investigative Site
  • Adana, Turkey, 01250
    • Novartis Investigative Site
  • Antakya / Hatay, Turkey, 31100
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Novartis Investigative Site
  • London, United Kingdom, W12 0HS
    • Novartis Investigative Site
  • London, United Kingdom, SE5 9RS
    • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Birmingham
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois Hospital and Health Sciences System
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Our Lady of the Lake Regional Medical Center
  • North Carolina
    • Greenville, North Carolina, United States, 27858
      • East Carolina University BrodySchool of Med. (3)
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • Univ of Tenn Health Sciences Ctr
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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; Other Names: SEG101; Drug: Standard of Care; HU/HC (hydroxyurea/hydroxycarbamide) and/or ACE (angiotensin-converting enzyme) inhibitors and/or ARBs (angiotensin-receptor blocker)
Active Comparator: standard of care; Patients in the standard of care alone arm will continue to receive their usual standard of care treatment.	Drug: Standard of Care; HU/HC (hydroxyurea/hydroxycarbamide) and/or ACE (angiotensin-converting enzyme) inhibitors and/or ARBs (angiotensin-receptor blocker)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2019
• Primary Completion (Actual): March 20, 2023
• Study Completion (Actual): March 20, 2023

Study Registration Dates

• First Submitted: August 9, 2019
• First Submitted That Met QC Criteria: August 9, 2019
• First Posted (Actual): August 12, 2019

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: chronic kidney disease; CKD; SCD; SEG101; renal function; Crizanlizumab; standard of care; Sickle cell nephropathy; albuminuria (ACR)
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Hematologic Diseases; Renal Insufficiency; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Anemia, Sickle Cell
• Other Study ID Numbers: CSEG101A2203; 2018-003608-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No