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

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ClinicalTrials.gov Identifier: NCT04053764
Recruitment Status : Active, not recruiting
First Posted : August 12, 2019
Last Update Posted : January 13, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease (SCD) Drug: Crizanlizuamb Drug: Standard of Care Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : December 10, 2019
Estimated Primary Completion Date : January 30, 2023
Estimated Study Completion Date : March 16, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arms and Interventions
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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 Name: 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)


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of patients with ≥ 30% decrease in albuminuria (ACR) at 12 months [ Time Frame: Baseline to 12 months ]
    Percentage of patients with ≥ 30% decrease in ACR at 12 months from baseline.


Secondary Outcome Measures :
  1. Change from baseline in albuminuria (ACR) at 3, 6, 9 and 12 months [ Time Frame: Baseline to 3, 6, 9, and 12 months ]
    Change in ACR from baseline to 3, 6, 9, and 12 months of treatment.

  2. Percentage of patients with ≥ 30% decrease in albuminuria (ACR) at 6 months [ Time Frame: Baseline to 6 months ]
    Percentage of patients with ≥ 30% decrease in ACR at 6 months from baseline

  3. Percentage of patients with protein to creatinine ratio (PCR) improvement at 12 months [ Time Frame: Baseline to 12 months ]
    Percentage of patients with PCR improvement at 12 months from baseline. Improvement: ≥ 20% decrease in PCR from baseline

  4. Percentage of patients with a stable protein to creatinine ratio (PCR) at 12 months [ Time Frame: Baseline to 12 months ]
    Percentage of patients with stable PCR at 12 months from baseline. Stable: within ± 20% change in PCR from baseline

  5. Percentage change in estimated glomerular filtration rate (eGFR) [ Time Frame: Baseline to 3, 6, 9, and 12 months ]
    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.

  6. Slope of albumin to creatinine ratio (ACR) decline [ Time Frame: Baseline to 3, 6, 9, and 12 months ]
    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.

  7. Slope of estimated glomerular filtration rate (eGFR) decline [ Time Frame: Baseline to 3, 6, 9, and 12 months ]
    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.

  8. Percentage of patients with progression of chronic kidney disease (CKD) at 12 months [ Time Frame: Baseline to 12 months ]
    Percentage of patients with progression of CKD from baseline to 12 months

  9. Immunogenicity: Levels of anti-drug antibodies (ADA) to crizanlizumab. [ Time Frame: Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months ]
    Levels of ADA to crizanlizumab at select time points

  10. Annualized rate of visits to emergency room (ER) and hospitalizations [ Time Frame: Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months ]
    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.

  11. Trough serum concentration (Ctrough) of crizanlizumab [ Time Frame: Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months ]
    Crizanlizumab pre-dose/trough pharmacokinetic samples will be taken at select time points


Eligibility Criteria
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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04053764


Locations
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United States, Alabama
University of Alabama Birmingham
Birmingham, Alabama, United States, 35233
United States, Illinois
University of Illinois Hospital and Health Sciences System
Chicago, Illinois, United States, 60612
United States, Louisiana
Our Lady of the Lake Regional Medical Center
Baton Rouge, Louisiana, United States, 70809
United States, North Carolina
East Carolina University BrodySchool of Med. (3)
Greenville, North Carolina, United States, 27858
United States, Tennessee
Univ of Tenn Health Sciences Ctr
Memphis, Tennessee, United States, 38163
United States, Texas
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
Brazil
Novartis Investigative Site
Rio de Janeiro, RJ, Brazil, 20.211-030
Novartis Investigative Site
Sao Paulo, SP, Brazil, 08270-070
Novartis Investigative Site
São Paulo, SP, Brazil, 01232-010
Novartis Investigative Site
Porto Alegre, Brazil, 90035-003
France
Novartis Investigative Site
Creteil, France, 94000
Novartis Investigative Site
Paris, France, 75015
Greece
Novartis Investigative Site
Athens, Greece, 115 27
Novartis Investigative Site
Larisa, Greece, 41221
Ireland
Novartis Investigative Site
Dublin 8, Ireland
Lebanon
Novartis Investigative Site
Tripoli, Lebanon, 1434
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1105 AZ
Panama
Novartis Investigative Site
Panama, Panama, 0801
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Turkey
Novartis Investigative Site
Adana, Turkey, 01250
Novartis Investigative Site
Adana, Turkey, 01330
Novartis Investigative Site
Antakya / Hatay, Turkey, 31100
United Kingdom
Novartis Investigative Site
London, United Kingdom, SE1 9RT
Novartis Investigative Site
London, United Kingdom, SE5 9RS
Novartis Investigative Site
London, United Kingdom, W12 0HS
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04053764    
Other Study ID Numbers: CSEG101A2203
2018-003608-38 ( EudraCT Number )
First Posted: August 12, 2019    Key Record Dates
Last Update Posted: January 13, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
SEG101
SCD
Crizanlizumab
Sickle cell nephropathy
chronic kidney disease
 CKD
albuminuria (ACR)
renal function
standard of care
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Anemia, Sickle Cell
Urologic Diseases
Renal Insufficiency
Anemia, Hemolytic, Congenital
 Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn