Clinical trial NCT04053764: Study Exploring the Effect of Crizanlizumab on Kidney Function in Patients With Chronic Kidney Disease Caused by Sickle Cell Disease
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle Cell Disease (SCD)
Keywords: SEG101
Sickle Cell Disease
SCD
Crizanlizumab
Sickle cell nephropathy
chronic kidney disease
CKD
albuminuria (ACR)
renal function
standard of care
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-08-12
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

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.

Primary outcomes:
measure: Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 12 Months
timeFrame: Baseline to 12 months
Secondary outcomes:
measure: Change From Baseline in Albuminuria (ACR) at 3, 6, 9 and 12 Months
timeFrame: Baseline to 3, 6, 9, and 12 months
measure: Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 6 Months
timeFrame: Baseline to 6 months
measure: Percentage of Participants With Protein/Creatinine Ratio (PCR) Improvement and Stable PCR at 12 Months
timeFrame: Baseline to 12 months
measure: Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline to 3, 6, 9, and 12 months
measure: Slope of Albumin to Creatinine Ratio (ACR) Decline
timeFrame: Baseline to 12 months
measure: Slope of Estimated Glomerular Filtration Rate (eGFR) Decline
timeFrame: Baseline to 12 months
measure: Percentage of Participants With Progression of Chronic Kidney Disease (CKD) at 12 Months
timeFrame: Baseline to 12 months
measure: Shift Table for Chronic Kidney Disease (CKD) Progression
timeFrame: Baseline and month 12
measure: Immunogenicity: Percentage of Participants With Anti-drug Antibodies (ADA) to Crizanlizumab
timeFrame: Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months
measure: Annualized Rate of Visits to Emergency Room (ER) and Hospitalizations
timeFrame: Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months
measure: Mean Serum Concentration (Ctrough) of Crizanlizumab
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Chicago
country: United States
facility: University of Illinois Hospital and Health Sciences System .
state: Illinois
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Regional Medic .
state: Louisiana
city: Greenville
country: United States
facility: East Carolina University BrodySchool of Med 3
state: North Carolina
city: Memphis
country: United States
facility: Univ of Tenn Health Sciences Ctr
state: Tennessee
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Paris 15
country: France
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Larisa
country: Greece
facility: Novartis Investigative Site
city: Dublin 8
country: Ireland
facility: Novartis Investigative Site
city: Tripoli
country: Lebanon
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Panama
country: Panama
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Adana
country: Turkey
facility: Novartis Investigative Site
city: Adana
country: Turkey
facility: Novartis Investigative Site
city: Antakya / Hatay
country: Turkey
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: