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 |
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Recruitment Status :
Active, not recruiting
First Posted : August 12, 2019
Last Update Posted : May 2, 2022
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Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
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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 Type : | Interventional (Clinical Trial) |
| 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 : | December 10, 2019 |
| Estimated Primary Completion Date : | December 1, 2022 |
| Estimated Study Completion Date : | March 16, 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Sickle cell disease
MedlinePlus related topics:
Kidney Diseases
Drug Information available for:
Crizanlizumab
| Arm | Intervention/treatment |
|---|---|
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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.
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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) |
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Active Comparator: standard of care
Patients in the standard of care alone arm will continue to receive their usual standard of care treatment.
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Drug: Standard of Care
HU/HC (hydroxyurea/hydroxycarbamide) and/or ACE (angiotensin-converting enzyme) inhibitors and/or ARBs (angiotensin-receptor blocker) |
Primary Outcome Measures :
- Percentage of patients with ≥ 30% decrease in albuminuria (ACR) at 12 months [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ 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. 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 [ 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. 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 [ 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. 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 [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
Information from the National Library of Medicine
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| 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
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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
Locations
| United States, Alabama | |
| University of Alabama Birmingham | |
| Birmingham, Alabama, United States, 35233 | |
| United States, Illinois | |
| University of Illinois Hospital and Health Sciences System | |
| Chicago, Illinois, United States, 60612 | |
| United States, Louisiana | |
| Our Lady of the Lake Regional Medical Center | |
| Baton Rouge, Louisiana, United States, 70809 | |
| United States, North Carolina | |
| East Carolina University BrodySchool of Med. (3) | |
| Greenville, North Carolina, United States, 27858 | |
| United States, Tennessee | |
| Univ of Tenn Health Sciences Ctr | |
| Memphis, Tennessee, United States, 38163 | |
| United States, Texas | |
| University of Texas Health Science Center at Houston | |
| Houston, Texas, United States, 77030 | |
| Brazil | |
| Novartis Investigative Site | |
| Rio de Janeiro, RJ, Brazil, 20.211-030 | |
| Novartis Investigative Site | |
| Sao Paulo, SP, Brazil, 08270-070 | |
| Novartis Investigative Site | |
| São Paulo, SP, Brazil, 01232-010 | |
| Novartis Investigative Site | |
| Porto Alegre, Brazil, 90035-003 | |
| France | |
| Novartis Investigative Site | |
| Creteil, France, 94000 | |
| Novartis Investigative Site | |
| Paris, France, 75015 | |
| Greece | |
| Novartis Investigative Site | |
| Athens, Greece, 115 27 | |
| Novartis Investigative Site | |
| Larisa, Greece, 41221 | |
| Ireland | |
| Novartis Investigative Site | |
| Dublin 8, Ireland | |
| Lebanon | |
| Novartis Investigative Site | |
| Tripoli, Lebanon, 1434 | |
| Netherlands | |
| Novartis Investigative Site | |
| Amsterdam, Netherlands, 1105 AZ | |
| Panama | |
| Novartis Investigative Site | |
| Panama City, Panama, 0801 | |
| Spain | |
| Novartis Investigative Site | |
| Sevilla, Andalucia, Spain, 41013 | |
| Novartis Investigative Site | |
| Barcelona, Catalunya, Spain, 08035 | |
| Novartis Investigative Site | |
| Madrid, Spain, 28009 | |
| Turkey | |
| Novartis Investigative Site | |
| Adana, Turkey, 01250 | |
| Novartis Investigative Site | |
| Adana, Turkey, 01330 | |
| Novartis Investigative Site | |
| Antakya / Hatay, Turkey, 31100 | |
| United Kingdom | |
| Novartis Investigative Site | |
| London, United Kingdom, SE1 9RT | |
| Novartis Investigative Site | |
| London, United Kingdom, SE5 9RS | |
| Novartis Investigative Site | |
| London, United Kingdom, W12 0HS | |
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
| 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: | May 2, 2022 |
| Last Verified: | April 2022 |
| 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. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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SEG101 SCD Crizanlizumab Sickle cell nephropathy chronic kidney disease |
CKD albuminuria (ACR) renal function standard of care |
Additional relevant MeSH terms:
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Kidney Diseases Renal Insufficiency, Chronic Anemia, Sickle Cell Urologic Diseases Renal Insufficiency Anemia, Hemolytic, Congenital |
Anemia, Hemolytic Anemia Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn |