Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04053764
Recruitment Status : Recruiting
First Posted : August 12, 2019
Last Update Posted : July 7, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 148 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 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
Actual Study Start Date : December 10, 2019
Estimated Primary Completion Date : October 9, 2023
Estimated Study Completion Date : January 20, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arm Intervention/treatment
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.
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)




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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

  4. 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

  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

  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

  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

  8. 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

  9. 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

  10. 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.

  11. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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


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


Contacts
Layout table for location contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

Locations
Show Show 34 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Layout table for additonal information
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: July 7, 2021
Last Verified: July 2021
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.


Layout table for additional information
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:
Layout table for MeSH terms
Kidney Diseases
Anemia, Sickle Cell
Urologic Diseases
Hematologic Diseases
Genetic Diseases, Inborn
Renal Insufficiency, Chronic
Renal Insufficiency
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hemoglobinopathies