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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)

Primary Purpose

Sickle Cell Disease (SCD)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Crizanlizuamb
Standard of Care
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease (SCD) focused on measuring SEG101, SCD, Crizanlizumab, Sickle cell nephropathy, chronic kidney disease, CKD, albuminuria (ACR), renal function, standard of care

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

  • University of Alabama Birmingham
  • University of Illinois Hospital and Health Sciences System
  • Our Lady of the Lake Regional Medical Center
  • East Carolina University BrodySchool of Med. (3)
  • Univ of Tenn Health Sciences Ctr
  • University of Texas Health Science Center at Houston
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

crizanlizumab + standard of care

standard of care

Arm 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.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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
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
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
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.
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.
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.
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
Immunogenicity: Levels of anti-drug antibodies (ADA) to crizanlizumab.
Levels of ADA to crizanlizumab at select time points
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.
Trough serum concentration (Ctrough) of crizanlizumab
Crizanlizumab pre-dose/trough pharmacokinetic samples will be taken at select time points

Full Information

First Posted
August 9, 2019
Last Updated
May 22, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04053764
Brief Title
Study Exploring the Effect of Crizanlizumab on Kidney Function in Patients With Chronic Kidney Disease Caused by Sickle Cell Disease
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
December 10, 2019 (Actual)
Primary Completion Date
March 20, 2023 (Actual)
Study Completion Date
March 20, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease (SCD)
Keywords
SEG101, SCD, Crizanlizumab, Sickle cell nephropathy, chronic kidney disease, CKD, albuminuria (ACR), renal function, standard of care

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
crizanlizumab + standard of care
Arm Type
Experimental
Arm 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.
Arm Title
standard of care
Arm Type
Active Comparator
Arm Description
Patients in the standard of care alone arm will continue to receive their usual standard of care treatment.
Intervention Type
Drug
Intervention Name(s)
Crizanlizuamb
Other Intervention Name(s)
SEG101
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Standard of Care
Intervention Description
HU/HC (hydroxyurea/hydroxycarbamide) and/or ACE (angiotensin-converting enzyme) inhibitors and/or ARBs (angiotensin-receptor blocker)
Primary Outcome Measure Information:
Title
Percentage of patients with ≥ 30% decrease in albuminuria (ACR) at 12 months
Description
Percentage of patients with ≥ 30% decrease in ACR at 12 months from baseline.
Time Frame
Baseline to 12 months
Secondary Outcome Measure Information:
Title
Change from baseline in albuminuria (ACR) at 3, 6, 9 and 12 months
Description
Change in ACR from baseline to 3, 6, 9, and 12 months of treatment.
Time Frame
Baseline to 3, 6, 9, and 12 months
Title
Percentage of patients with ≥ 30% decrease in albuminuria (ACR) at 6 months
Description
Percentage of patients with ≥ 30% decrease in ACR at 6 months from baseline
Time Frame
Baseline to 6 months
Title
Percentage of patients with protein to creatinine ratio (PCR) improvement at 12 months
Description
Percentage of patients with PCR improvement at 12 months from baseline. Improvement: ≥ 20% decrease in PCR from baseline
Time Frame
Baseline to 12 months
Title
Percentage of patients with a stable protein to creatinine ratio (PCR) at 12 months
Description
Percentage of patients with stable PCR at 12 months from baseline. Stable: within ± 20% change in PCR from baseline
Time Frame
Baseline to 12 months
Title
Percentage change in estimated glomerular filtration rate (eGFR)
Description
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.
Time Frame
Baseline to 3, 6, 9, and 12 months
Title
Slope of albumin to creatinine ratio (ACR) decline
Description
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.
Time Frame
Baseline to 3, 6, 9, and 12 months
Title
Slope of estimated glomerular filtration rate (eGFR) decline
Description
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.
Time Frame
Baseline to 3, 6, 9, and 12 months
Title
Percentage of patients with progression of chronic kidney disease (CKD) at 12 months
Description
Percentage of patients with progression of CKD from baseline to 12 months
Time Frame
Baseline to 12 months
Title
Immunogenicity: Levels of anti-drug antibodies (ADA) to crizanlizumab.
Description
Levels of ADA to crizanlizumab at select time points
Time Frame
Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months
Title
Annualized rate of visits to emergency room (ER) and hospitalizations
Description
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.
Time Frame
Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months
Title
Trough serum concentration (Ctrough) of crizanlizumab
Description
Crizanlizumab pre-dose/trough pharmacokinetic samples will be taken at select time points
Time Frame
Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of Illinois Hospital and Health Sciences System
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Our Lady of the Lake Regional Medical Center
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70809
Country
United States
Facility Name
East Carolina University BrodySchool of Med. (3)
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27858
Country
United States
Facility Name
Univ of Tenn Health Sciences Ctr
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38163
Country
United States
Facility Name
University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Novartis Investigative Site
City
Rio de Janeiro
State/Province
RJ
ZIP/Postal Code
20.211-030
Country
Brazil
Facility Name
Novartis Investigative Site
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
08270-070
Country
Brazil
Facility Name
Novartis Investigative Site
City
São Paulo
State/Province
SP
ZIP/Postal Code
01232-010
Country
Brazil
Facility Name
Novartis Investigative Site
City
Porto Alegre
ZIP/Postal Code
90035-003
Country
Brazil
Facility Name
Novartis Investigative Site
City
Creteil
ZIP/Postal Code
94000
Country
France
Facility Name
Novartis Investigative Site
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
115 27
Country
Greece
Facility Name
Novartis Investigative Site
City
Larisa
ZIP/Postal Code
41221
Country
Greece
Facility Name
Novartis Investigative Site
City
Dublin 8
Country
Ireland
Facility Name
Novartis Investigative Site
City
Tripoli
ZIP/Postal Code
1434
Country
Lebanon
Facility Name
Novartis Investigative Site
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Panama
ZIP/Postal Code
0801
Country
Panama
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Adana
ZIP/Postal Code
01250
Country
Turkey
Facility Name
Novartis Investigative Site
City
Adana
ZIP/Postal Code
01330
Country
Turkey
Facility Name
Novartis Investigative Site
City
Antakya / Hatay
ZIP/Postal Code
31100
Country
Turkey
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

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

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