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Completed

NCT Number: NCT04053764

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

The goal of the study was 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.

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Key information

Conditions

Sickle Cell Disease (SCD) Albuminuria Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Chronic Disease Congenital, Hereditary, and Neonatal Diseases and Abnormalities Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Kidney Diseases Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Proteinuria Renal Insufficiency Renal Insufficiency, Chronic Signs and Symptoms Urination Disorders Urogenital Diseases Urologic Diseases Urological Manifestations

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Rio de Janeiro, Brazil

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About this study

Approximately 50 patients were to be randomized 1:1 to receive either crizanlizumab (5 mg/kg) + standard of care or standard of care alone. Patients were stratified at randomization based on chronic kidney disease (CKD) risk category (moderate risk or high/very high risk) and hydroxyurea/hydroxycarbamide (HU/HC) prescription (Yes/No). The CKD risk categories used for stratification were based on both Estimated glomerular filtration rate(eGFR) and albuminuria assessed by Albumin/creatinine ratio (ACR).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Crizanlizuamb

Drug

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

Standard of care

Drug

HU/HC (hydroxyurea/hydroxycarbamide) and/or ACE (angiotensin-converting enzyme) inhibitors and/or ARBs (angiotensin-receptor blocker)

Primary outcomes

  1. Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 12 Months

    Time frame: Baseline to 12 months

    The effect of SEG101 on clinical disease activity was measured by at least 30% decrease in Albumin to Creatinine Ratio (ACR) from baseline to month 12. A reduction from baseline indicates improvement in patients.

Secondary outcomes

  1. Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months

    Time frame: Baseline to 3, 6, 9, and 12 months

    The effect of SEG101 on clinical disease activity was measured by the change in albuminuria (ACR) between baseline and month 3, baseline and month 6, baseline and month 9, baseline and month 12. A reduction from baseline indicates improvement in patients.

  2. Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 6 Months

    Time frame: Baseline to 6 months

    The effect of SEG101 on clinical disease activity was measured by at least 30% decrease in Albumin to Creatinine Ratio (ACR) from baseline to month 6. A reduction from baseline indicates improvement in patients.

  3. Percentage of Participants With Protein/Creatinine Ratio (PCR) Improvement and Stable PCR at 12 Months

    Time frame: Baseline to 12 months

    The effect of SEG101 on clinical disease activity was measured by counting patients who had Stable PCR: within ± 20% change from baseline to month 12. PCR improvement: ≥ 20% decrease in PCR from baseline indicates improvement in patients.

  4. Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)

    Time frame: Baseline to 3, 6, 9, and 12 months

    The percentage change in eGFR was calculated as the post-baseline eGFR value minus the baseline eGFR divided by the eGFR at baseline. A reduction from baseline indicates improvement in participants.

  5. Slope of Albumin to Creatinine Ratio (ACR) Decline

    Time frame: Baseline to 12 months

    The effect of SEG101 on clinical disease activity was measured by the slope of ACR decline between baseline and Month 12. A reduction from baseline indicates improvement in patients.

  6. Slope of Estimated Glomerular Filtration Rate (eGFR) Decline

    Time frame: Baseline to 12 months

    The effect of SEG101 on clinical disease activity was measured by the slope of eGFR between baseline and Month 12. The calculation of eGFR is based on the chronic kidney disease epidemiology collaboration (CKD-EPI) (for patients ≥ 18) and Creatinine-based "Bedside Schwartz" (for patients < 18) equations. A reduction in drop rate from baseline indicates improvement in patients.

  7. Percentage of Participants With Progression of Chronic Kidney Disease (CKD) at 12 Months

    Time frame: Baseline to 12 months

    The effect of SEG101 on clinical disease activity was measured by percentage of participants with CKD progression between baseline and Month 12. A reduction from baseline indicates improvement in participants.

    CKD progression is defined as an increase in CKD progression category, a 25% or greater drop in eGFR from baseline or at least 50% increase in ACR for patients with severe (A3) albuminuria and a doubling of albumin levels in patients with moderate (A2) albuminuria.

  8. Shift Table for Chronic Kidney Disease (CKD) Progression

    Time frame: Baseline and month 12

    The effect of SEG101 on clinical disease activity was measured by percentage of participants with CKD progression between baseline and Month 12. A reduction from baseline indicates improvement in patients.

  9. Immunogenicity: Percentage of Participants With 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

    The effect of SEG101 on clinical disease activity was measured by percentage of participants shifted to different worst post-baseline categories between baseline and Month 12. An increase in percentage shifting from higher category to lower category indicates improvement in patients.

    Baseline is defined as the last non-missing value prior to the first dose.

  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

    The effect of SEG101 on clinical disease activity was measured by summarizing the annualized rate of visits to ER and hospitalizations between baseline and 1 year 4 months. Annualized rate of hospitalizations and ER visits due to VOC =(Number of ER or hospitalizations reported until End date x 365.25)/(End date-date of first dose of study treatment+1). A reduction from baseline indicates improvement in patients.

  11. Mean Serum Concentration (Ctrough) of Crizanlizumab

    Time frame: Pre-dose and 336 hours post-dose on Week 3 Day 1; pre-dose and 672 hours post dose on Week 11 Day 1, Week 23 Day 1 and Week 39 Day 1; and 672 hours post dose on Week 53 Day 1

    The effect of SEG101 on clinical disease activity was measured by checking the concentration of the Drug in serum at different time points.

    Crizanlizumab pre-dose/trough pharmacokinetic samples were taken at select time points.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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)

Acronym: STEADFAST

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Aug 12, 2019
Registry last updated
Oct 9, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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