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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04053764

Collaborator

(none)

Enrollment

Locations

Arms

39.2

Anticipated Duration (Months)

2.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

58 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 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)

Actual Study Start Date :

Dec 10, 2019

Anticipated Primary Completion Date :

Nov 30, 2022

Anticipated Study Completion Date :

Mar 16, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: crizanlizumab + standard of care 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.	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 Names: 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)

Arm

Intervention/Treatment

Experimental: crizanlizumab + standard of care

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.

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 Names:

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)

Outcome Measures

Primary Outcome Measures

Percentage of patients with ≥ 30% decrease in albuminuria (ACR) at 12 months [Baseline to 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 [Baseline to 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 [Baseline to 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 [Baseline to 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 [Baseline to 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) [Baseline to 3, 6, 9, and 12 months]
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 [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. 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 [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. 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 [Baseline to 12 months]
Percentage of patients with progression of CKD from baseline to 12 months
Immunogenicity: Levels of anti-drug antibodies (ADA) to crizanlizumab. [Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months]
Levels of ADA to crizanlizumab at select time points
Annualized rate of visits to emergency room (ER) and hospitalizations [Baseline to follow-up period (at select time points), assessed up to approximately 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 [Baseline to follow-up period (at select time points), assessed up to approximately 1 year and 4 months]
Crizanlizumab pre-dose/trough pharmacokinetic samples will be taken at select time points

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts 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 ≥

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Birmingham	Birmingham	Alabama	United States	35233
2	University of Illinois Hospital and Health Sciences System	Chicago	Illinois	United States	60612
3	Our Lady of the Lake Regional Medical Center	Baton Rouge	Louisiana	United States	70809
4	East Carolina University BrodySchool of Med. (3)	Greenville	North Carolina	United States	27858
5	Univ of Tenn Health Sciences Ctr	Memphis	Tennessee	United States	38163
6	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030
7	Novartis Investigative Site	Rio de Janeiro	RJ	Brazil	20.211-030
8	Novartis Investigative Site	Sao Paulo	SP	Brazil	08270-070
9	Novartis Investigative Site	São Paulo	SP	Brazil	01232-010
10	Novartis Investigative Site	Porto Alegre		Brazil	90035-003
11	Novartis Investigative Site	Creteil		France	94000
12	Novartis Investigative Site	Paris		France	75015
13	Novartis Investigative Site	Athens		Greece	115 27
14	Novartis Investigative Site	Larisa		Greece	41221
15	Novartis Investigative Site	Dublin 8		Ireland
16	Novartis Investigative Site	Tripoli		Lebanon	1434
17	Novartis Investigative Site	Amsterdam		Netherlands	1105 AZ
18	Novartis Investigative Site	Panama City		Panama	0801
19	Novartis Investigative Site	Sevilla	Andalucia	Spain	41013
20	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
21	Novartis Investigative Site	Madrid		Spain	28009
22	Novartis Investigative Site	Adana		Turkey	01250
23	Novartis Investigative Site	Adana		Turkey	01330
24	Novartis Investigative Site	Antakya / Hatay		Turkey	31100
25	Novartis Investigative Site	London		United Kingdom	SE1 9RT
26	Novartis Investigative Site	London		United Kingdom	SE5 9RS
27	Novartis Investigative Site	London		United Kingdom	W12 0HS