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

NCT04053764 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CSEG101A22032018-003608-38
• Study Type: interventional
• Target: 58
• Locations: 11 countries
• Sites: 24

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.

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With ≥ 30% Decrease in Albuminuria (ACR) at 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.

  Baseline to 12 months

Secondary Outcomes (11)

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

  Baseline to 3, 6, 9, and 12 months

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

  Baseline to 6 months

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

  Baseline to 12 months

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

  Baseline to 3, 6, 9, and 12 months

• Slope of Albumin to Creatinine Ratio (ACR) Decline

  Baseline to 12 months

Study Arms (2)

crizanlizumab + standard of care

EXPERIMENTAL

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; Drug: Standard of Care

standard of care

ACTIVE COMPARATOR

Patients in the standard of care alone arm will continue to receive their usual standard of care treatment.

Drug: Standard of Care

Interventions

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

Also known as: SEG101

crizanlizumab + standard of care

Standard of Care DRUG

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

crizanlizumab + standard of care; standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (24)

University of Alabama Birmingham

Birmingham, Alabama, 35233, United States

Location

University of Illinois Hospital and Health Sciences System .

Chicago, Illinois, 60612, United States

Location

Our Lady of the Lake Regional Medic .

Baton Rouge, Louisiana, 70809, United States

Location

East Carolina University BrodySchool of Med 3

Greenville, North Carolina, 27858, United States

Location

Univ of Tenn Health Sciences Ctr

Memphis, Tennessee, 38163, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 20.211-030, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01232-010, Brazil

Location

Novartis Investigative Site

Porto Alegre, 90035-003, Brazil

Location

Novartis Investigative Site

Créteil, 94010, France

Location

Novartis Investigative Site

Paris, 75015, France

Location

Novartis Investigative Site

Athens, 115 27, Greece

Location

Novartis Investigative Site

Larissa, 41221, Greece

Location

Novartis Investigative Site

Dublin, DO8, Ireland

Location

Novartis Investigative Site

Tripoli, 1434, Lebanon

Location

Novartis Investigative Site

Amsterdam, 1105 AZ, Netherlands

Location

Novartis Investigative Site

Panama City, 0801, Panama

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Adana, 01250, Turkey (Türkiye)

Location

Novartis Investigative Site

Adana, 01330, Turkey (Türkiye)

Location

Novartis Investigative Site

Antakya / Hatay, 31100, Turkey (Türkiye)

Location

Novartis Investigative Site

London, SE1 9RT, United Kingdom

Location

Novartis Investigative Site

London, SE5 9RS, United Kingdom

Location

Novartis Investigative Site

London, W12 0HS, United Kingdom

Location

Related Publications (2)

• Abbasi M, Srivastava A, Saraf SL. Management of Kidney Disease with Sickle Cell Disease. J Am Soc Nephrol. 2025 Oct 1;36(10):2041-2054. doi: 10.1681/ASN.0000000804. Epub 2025 Jun 26.

  PMID: 40569673 DERIVED

• Obadina M, Wilson S, Derebail VK, Little J. Emerging Therapies and Advances in Sickle Cell Disease with a Focus on Renal Manifestations. Kidney360. 2023 Jul 1;4(7):997-1005. doi: 10.34067/KID.0000000000000162. Epub 2023 May 31.

  PMID: 37254256 DERIVED

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Anemia, Sickle Cell; Renal Insufficiency, Chronic; Albuminuria

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-3000

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2019
• First Posted: August 12, 2019
• Study Start: December 10, 2019
• Primary Completion: March 20, 2023
• Study Completion: March 20, 2023
• Last Updated: October 9, 2024
• Results First Posted: June 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

IE (1); GR (2); GB (3); ES (1); US (6); BR (3); FR (2); NL (1); PA (1); TU (3); LE (1)