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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 : Recruiting
First Posted : August 12, 2019
Last Update Posted : May 3, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE August 9, 2019
First Posted Date  ICMJE August 12, 2019
Last Update Posted Date May 3, 2021
Actual Study Start Date  ICMJE December 10, 2019
Estimated Primary Completion Date December 21, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 9, 2020)
Percentage of patients with ≥ 30% decrease in albuminuria (ACR) [ Time Frame: Baseline to 12 months ]
Proportion of patients with ≥ 30% decrease in ACR at 12 months compared to baseline.
Original Primary Outcome Measures  ICMJE
 (submitted: August 9, 2019)
Percentage of patients with ≥ 30% decrease in albuminuria (ACR) [ Time Frame: Baseline to 12 months ]
To evaluate the effect of crizanlizumab + standard of care compared to standard of care alone on albuminuria (ACR) decrease
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 9, 2020)
  • Mean change from baseline in albuminuria (ACR) [ Time Frame: Baseline to 3, 6, 9, and 12 months ]
    Mean change in ACR from baseline to 3, 6, 9, and 12 months of treatment.
  • Percentage of patients with ≥ 30% decrease in albuminuria (ACR) [ Time Frame: Baseline to 6 months ]
    Proportion of patients with ≥ 30% decrease in ACR at 6 months compared to baseline
  • Percentage of patients with ≥ 20% improvement of protein to creatinine ratio (PCR) [ Time Frame: Baseline to 12 months ]
    Proportion of patients with PCR improvement at 12 months compared to baseline. Improvement: ≥ 20% decrease in PCR from baseline
  • Percentage of patients with a stable (within ± 20% change) protein to creatinine ratio (PCR) [ Time Frame: Baseline to 12 months ]
    Proportion of patients with stable PCR at 12 months compared to baseline. Stable: within ± 20% change in PCR from baseline
  • 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
  • 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
  • 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
  • Percentage of patients with progression of chronic kidney disease (CKD) [ Time Frame: Baseline to 12 months ]
    Proportion of patients with progression of CKD from baseline to 12 months
  • Immunogenicity: measurement of anti-drug antibodies (ADA) to crizanlizumab. [ Time Frame: Baseline to follow-up period, at select time points approx. 1 year and 4 months ]
    Measurement of ADA to crizanlizumab at select time points
  • Annualized rate of visits to emergency room (ER) and hospitalizations [ Time Frame: Baseline to follow-up period, approx. 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.
  • Trough serum concentration (Ctrough) of crizanlizumab [ Time Frame: Baseline to follow-up period, at select time points approx. 1 year and 4 months ]
    Crizanlizumab pre-dose/trough pharmacokinetic samples will be taken at select time points
Original Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2019)
  • Mean change in albuminuria (ACR) [ Time Frame: Baseline to 3, 6, 9, and 12 months ]
    To evaluate the effect of crizanlizumab + standard of care compared to standard of care alone on change in albuminuria (ACR)
  • Percentage of patients with ≥ 30% decrease in albuminuria (ACR) [ Time Frame: Baseline to 6 months ]
    To evaluate the effect of crizanlizumab + standard of care compared to standard of care alone on albuminuria (ACR) decrease
  • Percentage of patients with ≥ 20% improvement of protein to creatinine ratio (PCR) [ Time Frame: Baseline to 12 months ]
    To evaluate the effect of crizanlizumab + standard of care compared to standard of care alone on protein to creatinine ratio (PCR)
  • Percentage of patients with a stable (within ± 20% change) protein to creatinine ratio (PCR) [ Time Frame: Baseline to 12 months ]
    To evaluate the effect of crizanlizumab + standard of care compared to standard of care alone on protein to creatinine ratio (PCR)
  • Percentage change in estimated glomerular filtration rate (eGFR) [ Time Frame: Baseline to 3, 6, 9 and 12 months ]
    To evaluate the effect of crizanlizumab + standard of care compared to standard of care alone on the percentage change in estimated glomerular filtration rate (eGFR)
  • Slope of albumin to creatinine ratio (ACR) decline [ Time Frame: Baseline, 3, 6, 9, and 12 months ]
    To evaluate the effect of crizanlizumab + standard of care compared to standard of care alone on albumin to creatinine ratio (ACR) decline rate
  • Slope of estimated glomerular filtration rate (eGFR) decline [ Time Frame: Baseline to 3, 6, 9 and 12 months ]
    To evaluate the effect of crizanlizumab + standard of care compared to standard of care alone on estimated glomerular filtration rate (eGFR) decline rate
  • Percentage of patients with progression of chronic kidney disease (CKD) [ Time Frame: Baseline to 12 months ]
    To evaluate the effect of crizanlizumab + standard of care compared to standard of care alone on the progression of chronic kidney disease (CKD)
  • Immunogenicity: measurement of anti-drug antibodies (ADA) to crizanlizumab [ Time Frame: Baseline to follow-up period, at select time points approx. 1 year and 4 months ]
    To assess the immunogenicity of crizanlizumab over the study period
  • Annualized rate of visits to emergency room and hospitalizations [ Time Frame: Baseline to follow-up period, approx. 1 year and 4 months ]
    To evaluate healthcare resource utilization (visits to emergency room and hospitalizations) due to Acute Kidney Injury (AKI) events, Vaso-occlusive crisis (VOCs), or other Sickle Cell Disease (SCD) complications.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Exploring the Effect of Crizanlizumab on Kidney Function in Patients With Chronic Kidney Disease Caused by Sickle Cell Disease
Official Title  ICMJE A Phase II, Multicenter, Randomized, Open Label Two Arm Study Comparing the Effect of Crizanlizumab + Standard of Care to Standard of Care Alone on Renal Function in Sickle Cell Disease Patients ≥ 16 Years With Chronic Kidney Disease Due to Sickle Cell Nephropathy
Brief Summary The goal of the study is to compare the efficacy and safety of crizanlizumab + standard of care to standard of care alone on renal function in sickle cell disease patients ≥ 16 years with chronic kidney disease due to sickle cell nephropathy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease (SCD)
Intervention  ICMJE
  • 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)
Study Arms  ICMJE
  • Experimental: crizanlizumab + standard of care
    5 mg/kg by intravenous 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.
    Interventions:
    • Drug: Crizanlizuamb
    • Drug: Standard of Care
  • Active Comparator: standard of care
    Patients in the standard of care alone arm will continue to receive their usual standard of care treatment.
    Intervention: Drug: Standard of Care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 30, 2021)
148
Original Estimated Enrollment  ICMJE
 (submitted: August 9, 2019)
170
Estimated Study Completion Date  ICMJE April 4, 2024
Estimated Primary Completion Date December 21, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Listed Location Countries  ICMJE Brazil,   France,   Greece,   Italy,   Netherlands,   Panama,   South Africa,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04053764
Other Study ID Numbers  ICMJE CSEG101A2203
2018-003608-38 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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.

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP