Study of Dose Confirmation and Safety of Crizanlizumab in Pediatric Sickle Cell Disease Patients

NCT03474965 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CSEG101B22012017-001747-12
• Study Type: interventional
• Target: 117
• Locations: 14 countries
• Sites: 35

Brief Summary

The purpose of this study was to confirm and to establish appropriate dosing and to evaluate the safety in pediatric participants ages 2 to \<18 years with a history of Vaso-Occlusive Crisis (VOC) with or without Hydroxyurea/Hydroxycarbamide (HU/HC), receiving crizanlizumab for 2 years. The efficacy and safety of crizanlizumab was previously demonstrated in adults with sickle cell disease. The approach was to extrapolate from the pharmacokinetics (PK)/pharmacodynamics (PD) already established in the adult population. The study was designed as a Phase II, multicenter, open-label study.

Conditions

Sickle Cell Disease (SCD)

Keywords

SEG101; Sickle cell disease; SCD; crizanlizumab; pediatric; pharmacokinetic; P-selectin; Covid-19; Coronavirus disease 2019

Outcome Measures

Primary Outcomes (6)

• Pharmacokinetics (PK): AUCd15 of Crizanlizumab After First Dose - Part A

  The area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) following the first dose. AUCd15 was calculated based on serum concentrations of crizanlizumab.

  Day 1 to Day 15

• Pharmacokinetics (PK) - AUCtau for Serum Crizanlizumab After Multiple Doses - Part A - Steady State

  The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).

  Week 15 - Steady state

• Pharmacokinetics (PK) - Cmax for Crizanlizumab After First Dose and Multiple Doses - Part A - Steady State

  The maximum (peak) observed, serum, drug concentration after single or multiple dose administration (mass x volume-1)

  Week 1 (after first dose) and Week 15 (steady state)

• Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab After First Dose - Part A - AUCd15

  The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) following the first dose. AUCd15 was calculated based on P-selectin inhibition curves.

  Day 1 to Day 15

• Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab - Part A - AUCtau After Multiple Dose - Steady State

  The AUC of %inhibition calculated to the end of a dosing interval (tau) after multiple dose. AUCtau was calculated based on P-selectin inhibition curves.

  Week 15 - Steady state

• Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability

  An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject

  Adverse events are reported from the first dose of study treatment until end of study treatment Week 103 plus 105 days post-treatment follow-up, up to a maximum timeframe of approximately 2 years and 3.25 months.

Secondary Outcomes (21)

• Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic / Emergency Room (ER) / Hospital

  Baseline, Year 1 and Year 2

• Annualized Rate Vaso Occlusive Crisis (VOC) Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With the Patient)

  Up to Year 2

• Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Uncomplicated Pain Crisis

  Up to Year 2

• Annualized Rate Vaso Occlusive Crisis (VOC) Events Leading to Healthcare Visit - Acute Chest Syndrome

  Up to Year 2

• Annualized Rate Vaso Occlusive Crisis (VOC) Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With the Patient) - Hepatic Sequestration

  Up to Year 2

Study Arms (1)

Crizanlizumab

EXPERIMENTAL

SEG101 (crizanlizumab) 5 mg/kg or 8 mg/kg i.v. administered on Week 1 Day 1, Week3 Day 1 and Day 1 of every 4-week cycle for up to 2 years. The initial dose of crizanlizumab was 5 mg/kg dose for Group 1 and Group 2 Part A. It was later adjusted to 8.5 mg/kg for Group 2 and 3 based on final dose confirmation from emerging PK data analysis and safety considerations determined in Part A of the study.

Drug: Crizanlizumab

Interventions

Crizanlizumab DRUG

Crizanlizumab (SEG101) 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

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female patients ages 2 to \<18 years
• Confirmed diagnosis of SCD (any genotype including HbSS, HbSC, HbSβ0-thalassemia, HbSβ+-thalassemia patients, and others) by hemoglobin electrophoresis or/and high-performance liquid chromatography (HPLC) \[performed locally\]. Confirmation of diagnosis by two accepted methods is recommended.
• Experienced at least 1 VOC within the preceding 12 months prior to screening, as determined by medical history. Prior VOC must have resolved at least 7 days prior to the first dose in the study and must include all the following: a.the occurrence of appropriate symptoms (see VOC definition in Section 7.2.1.1), b.either a visit to a medical facility or healthcare professional, c.receipt of oral/parenteral opioid or parenteral NSAIDs
• If receiving HU/HC, L-glutamine or erythropoietin stimulating agent, must have been receiving the drug consistently for at least 6 months prior to screening and plan to continue taking it at the same dose and schedule during the trial. Patients who have not been receiving such drugs must have been off them for at least 6 months prior to screening. . Dose alterations of HU/HC, L-glutamine or erythropoietin stimulating agent during Part A are not allowed, and if this occurs, the participant will enter directly to Part B.
• Received standard age-appropriate care for SCD, including penicillin prophylaxis, pneumococcal immunization, and parental education.
• Performance status: Karnofsky ≥ 50% for patients \>10 years of age, and Lansky ≥ 50 for patients ≤ 10 years of age.
• Patient must meet the following laboratory values prior to Week 1 Day 1: Absolute Neutrophil Count ≥1.0 x 109/L , Platelets ≥75 x 109/L, Hemoglobin (Hgb) \> 5.5 g/dL
• Patient must have adequate renal and hepatic function as defined:Estimated Glomerular filtration rate (eGFR) ≥ 75 mL/min/1.73 m2 using Schwartz formula, Direct (conjugated) bilirubin ≤ 2.0 x ULN, Alanine transaminase (ALT) ≤ 3.0 x ULN,
• Transcranial Doppler (TCD) for patients aged 2 to \< 16 years at time of screening, with HbSS, HbSβ0-thalassemia, and HbSD disease indicating low risk for stroke (per investigator). Please refer to Section 7.2.2.6 for details
• Written informed consent/assent, according to local guidelines, signed by the patient and / or by the parents or legal guardian prior to any study related screening procedures are performed.
• Female of non-childbearing potential or with negative serum pregnancy test on Screening and a negative urine pregnancy test (dipstick) prior to dosing on Day 1.

You may not qualify if:

• History of stem cell transplant.
• Received any blood products within 30 days prior to Week 1 Day 1 dosing.
• Plan to participate in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) or undergo exchange transfusions/plasmapheresis during the study. Patients requiring episodic transfusion (simple or exchange) in response to worsened anemia or VOC are permitted.
• Patients with bleeding disorders
• Contraindication or hypersensitivity to any drug from similar class as study drug or to any excipients of the study drug formulation.
• History of severe hypersensitivity reaction to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction 8.Received a monoclonal antibody or immunoglobulin-based therapy within 6 months of Screening, or has documented immunogenicity to a prior monoclonal antibody.
• Received active treatment on another investigational trial within 30 days (or 5 half -lives of that agent, whichever is greater) prior to Screening or plans to participate in another investigational drug trial.
• Pregnant females or females who have given birth within the past 90 days or who are breastfeeding.
• \. Any documented history of a clinical stroke or intracranial hemorrhage, or an uninvestigated neurologic finding within the past 12 months. Silent infarcts (only present on imaging) are not excluding patients from study participation 12.Any abnormal TCD within the past 12 months. 13.Use of therapeutic anticoagulation (prophylactic doses permitted) or antiplatelet therapy (other than aspirin) within the 10 days prior to Week 1 Day 1 dosing.
• Hospitalized within 7 days prior to Week 1 Day 1 dosing. 15.Planning to undergo a major surgical procedure during the duration of the study.
• Planning to initiate or terminate HU/HC or L-glutamine while on study (except if needed to terminate for safety reasons).
• Patient with active human immunodeficiency virus (HIV) infection (detectable viral load).
• Patients with known active Hepatitis B infection. 19.Patients with known Hepatitis C history. 20.Significant active infection or immune deficiency (including chronic use of immunosuppressive drugs) in the opinion of the investigator.
• Has a serious mental or physical illness, which, in the opinion of the Investigator would compromise participation in the study.
• Any condition which, in the opinion of the investigator, is likely to interfere with the successful collection of the measurements required for the study 24.Resting QTcF ≥450 msec at pretreatment (baseline) for patients under 12 years of age and ≥450 msec for males and ≥460 msec for female patients 12 years and older.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (35)

University Of Alabama

Birmingham, Alabama, 35233, United States

Location

Childrens National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Joe DiMaggio Childrens Hospital

Hollywood, Florida, 33021, United States

Location

Childrens Healthcare of Atlanta

Atlanta, Georgia, 30342, United States

Location

Childrens Hosp Boston Dept of Hematology

Boston, Massachusetts, 02115, United States

Location

Childrens Hospital at Montefiore

The Bronx, New York, 10467, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Childrens Hospital Of Philadelphia

Philadelphia, Pennsylvania, 19104-4399, United States

Location

Medical Uni of South Carolina

Charleston, South Carolina, 29425, United States

Location

Cook Childrens Medical Center

Fort Worth, Texas, 76104, United States

Location

Novartis Investigative Site

Brussels, 1000, Belgium

Location

Novartis Investigative Site

Laken, 1020, Belgium

Location

Novartis Investigative Site

Liège, 4000, Belgium

Location

Novartis Investigative Site

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Novartis Investigative Site

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01232-010, Brazil

Location

Novartis Investigative Site

Montreal, Quebec, H3T 1C5, Canada

Location

Novartis Investigative Site

Cali, Valle del Cauca Department, 760012, Colombia

Location

Novartis Investigative Site

Montería, 230004, Colombia

Location

Novartis Investigative Site

Paris, 75015, France

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Nagpur, Maharashtra, 440009, India

Location

Novartis Investigative Site

Padua, PD, 35128, Italy

Location

Novartis Investigative Site

Orbassano, TO, 10043, Italy

Location

Novartis Investigative Site

Beirut, 1107 2020, Lebanon

Location

Novartis Investigative Site

Tripoli, 1434, Lebanon

Location

Novartis Investigative Site

Muscat, 123, Oman

Location

Novartis Investigative Site

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Adana, 01330, Turkey (Türkiye)

Location

Novartis Investigative Site

Mersin, 33110, Turkey (Türkiye)

Location

Novartis Investigative Site

London, SE1 7EH, United Kingdom

Location

Related Publications (1)

• Del Pozo Martin Y. 2021 ASH annual meeting. Lancet Haematol. 2022 Feb;9(2):e92-e93. doi: 10.1016/S2352-3026(21)00384-7. Epub 2021 Dec 16. No abstract available.

  PMID: 34922648 DERIVED

Related Links

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

MeSH Terms

Conditions

Anemia, Sickle Cell; COVID-19

Interventions

crizanlizumab

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; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2018
• First Posted: March 23, 2018
• Study Start: October 1, 2018
• Primary Completion: November 6, 2024
• Study Completion: November 6, 2024
• Last Updated: October 16, 2025
• Results First Posted: July 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

OM (1); IN (1); TU (2); FR (1); BE (3); BR (3); US (12); ES (3); CA (1); LE (2); DE (1); CO (2); IT (2); GB (1)