Last Update: Feb 02, 2024
A Phase 2,Multicenter,Open-Label Study to Assess Appropriate Dosing and to Evaluate Safety of Crizanlizumab,With or Without Hydroxyurea/Hydroxycarbamide,in Sequential,Descending Age Groups of Pediatric Sickle Cell Disease Patients With Vaso-Occlusive Crisis
ClinicalTrials.gov Identifier:
Novartis Reference Number:CSEG101B2201
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

The purpose of the Phase 2 CSEG101B2201 study is to confirm and to establish appropriate dosing and to evaluate the safety in pediatric participants ages 6 months to <18 years with a history of VOC with or without HU/HC, receiving crizanlizumab for 2 years. The efficacy and safety of crizanlizumab was already demonstrated in adults with sickle cell disease. The approach is to extrapolate from the PK/pharmacodynamics (PD) already established in the adult population. The study is designed as a Phase II, multicenter, open-label study.

Sickle Cell Disease (SCD)
Phase 2
Recruiting
119
Oct 01, 2018
Jun 12, 2026
All
6 Years - 17 Years (Child)

Interventions

Drug

Crizanlizumab

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.

Eligibility Criteria

Inclusion Criteria:

Male or female patients ages 2 to <18 years (Group 3 will be expanded to allow enrolment of patients ages 6 to <24 months (and at least 7 kg) in Part B once the appropriate dose is confirmed in 2 to <6 year old participants).
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.

Exclusion Criteria:

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

6.Contraindication or hypersensitivity to any drug from similar class as study drug or to any excipients of the study drug formulation.

7.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.

9.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.

10.Pregnant females or females who have given birth within the past 90 days or who are breastfeeding.

11.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.

14.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.

16.Planning to initiate or terminate HU/HC or L-glutamine while on study (except if needed to terminate for safety reasons).

17.Patient with active human immunodeficiency virus (HIV) infection (detectable viral load).

18.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.

21.Malignant disease. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; any completely resected carcinoma in situ.

22.Has a serious mental or physical illness, which, in the opinion of the Investigator would compromise participation in the study.

23.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.

25.Cardiac or cardiac repolarization abnormality, including any of the following: a. History of myocardial infarction (MI), uncontrolled congestive heart failure, unstable angina, or coronary bypass graft (CABG) within 6 months prior to starting study treatment, b. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (bifascicular block, Mobitz Type II, and third degree AV block), c. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome ( Risk factors for Torsade de Pointes (TdP), including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/ symptomatic bradycardia, Inability to determine the QTcF).

26. Sexually active females who are unwilling to comply with reliable method of birth control until 15 weeks following last dose of study drug.

28.Not able to understand and to comply with study instructions and requirements.

29.Patients who are an employee of the sponsor or investigator or otherwise dependent on them.

30.Patients who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.

31.Patients who received prior crizanlizumab treatment and/or other selectin targeting agents are not allowed 32.Patients having taken voxelotor less than 30 days prior to Screening, or planning to take voxelotor while on study are not allowed.

Study Location

Novartis Investigative Site

Recruiting

Edegem,Antwerpen,2650,Belgium

Novartis Investigative Site

Recruiting

Brussel,1000,Belgium

Novartis Investigative Site

Recruiting

Laeken,1020,Belgium

Novartis Investigative Site

Recruiting

Liege,4000,Belgium

Novartis Investigative Site

Recruiting

Ribeirao Preto,SP,14048-900,Brazil

Novartis Investigative Site

Recruiting

Salvador,BA,41253-190,Brazil

Novartis Investigative Site

Recruiting

São Paulo,SP,01232-010,Brazil

Novartis Investigative Site

Recruiting

Montreal,Quebec,H3T 1C5,Canada

Novartis Investigative Site

Recruiting

Monteria,230004,Colombia

Novartis Investigative Site

Recruiting

Cali,Valle Del Cauca,760012,Colombia

Novartis Investigative Site

Recruiting

Paris 15,75015,France

Novartis Investigative Site

Recruiting

Heidelberg,Baden Wuerttemberg,69120,Germany

Novartis Investigative Site

Recruiting

Koeln,50937,Germany

Novartis Investigative Site

Recruiting

Berlin,13353,Germany

Novartis Investigative Site

Recruiting

Modena,MO,41124,Italy

Novartis Investigative Site

Recruiting

Orbassano,TO,10043,Italy

Novartis Investigative Site

Recruiting

Padova,PD,35128,Italy

Novartis Investigative Site

Recruiting

Tripoli,1434,Lebanon

Novartis Investigative Site

Recruiting

Beirut,1107 2020,Lebanon

Novartis Investigative Site

Recruiting

Muscat,123,Oman

Novartis Investigative Site

Recruiting

Valencia,Comunidad Valenciana,46026,Spain

Novartis Investigative Site

Recruiting

Madrid,28009,Spain

Novartis Investigative Site

Recruiting

Barcelona,Catalunya,08035,Spain

Novartis Investigative Site

Recruiting

Esplugues De Llobregat,Barcelona,08950,Spain

Novartis Investigative Site

Recruiting

Palma De Mallorca,Islas Baleares,07120,Spain

Novartis Investigative Site

Recruiting

Adana,01330,Turkey

Novartis Investigative Site

Recruiting

Mersin,33343,Turkey

Novartis Investigative Site

Recruiting

London,SE1 7EH,United Kingdom

Novartis Investigative Site

Recruiting

London,SE5 8AD,United Kingdom

Novartis Investigative Site

Recruiting

Manchester,M13 9WL,United Kingdom

Novartis Investigative Site

Recruiting

Chicago,Mariel Galvan (773-702-2084) email: [email protected] -- Radhika Peddinti,60637 - Illinois,United States

Novartis Investigative Site

Recruiting

Boston,Erika Tavares (617-355-7700) email: [email protected] -- Matthew M Heeney,02115 - Massachusetts,United States

Novartis Investigative Site

Recruiting

Durham,Patrick Barrera (919-684-1018) email: [email protected] -- Jennifer Rothman,27710 - North Carolina,United States

Novartis Investigative Site

Recruiting

Bronx,Jill Fillipelli (718-741-2384) email: [email protected] -- Deepa Manwani,10467 - New York,United States

Novartis Investigative Site

Recruiting

Philadelphia,Julia Sabrick (267-426-9338) email: [email protected] -- Helge D Hartung,19104-4399 - Pennsylvania,United States

Novartis Investigative Site

Recruiting

Hollywood,Nathalie Espinosa (954-265-5324) email: [email protected] -- Anne Schaefer,33021 - Florida,United States

Novartis Investigative Site

Recruiting

Washington,Stefanie Jesus Margulies (+1 202 476 5000) email: [email protected] -- Andrew Campbell,20010 - District of Columbia,United States

Novartis Investigative Site

Recruiting

Phoenix,Erica Sieber (602-546-4702) email: [email protected] -- Sanjay Shah,85016 - Arizona,United States

Novartis Investigative Site

Recruiting

Houston,Batha Tariq (832-822-1804) email: [email protected] -- Venee Tubman,77030 - Texas,United States

Novartis Investigative Site

Recruiting

Gainesville,Melissa Lingis (353-273-9120) email: [email protected] -- John Fort,32610 - Florida,United States

Novartis Investigative Site

Recruiting

Memphis,Olivia McGregor (901-595-7188) email: [email protected] -- Jeremie Heath Estepp,38105 - Tennessee,United States

Novartis Investigative Site

Recruiting

Charleston,Kreighton M. Milks email: [email protected] -- Shayla Bergmann,29425 - South Carolina,United States

Novartis Investigative Site

Recruiting

Greenville,Melissa Johnson (252-744-4676) email: [email protected] -- Beng Fuh,27834 - North Carolina,United States

Novartis Investigative Site

Recruiting

Chicago,Kayla Jones (+1 312 227 4811) email: [email protected] -- Astrid Kyle Mack,60611 - Illinois,United States

Novartis Investigative Site

Recruiting

Birmingham,Christy Patrick (205-638-9285) email: [email protected] -- Thomas Howard,35233 - Alabama,United States

Novartis Investigative Site

Recruiting

Hackensack,Elana Smilow (551-996-5437) email: [email protected] -- Stacey Rifkin-Zenenberg,07601 - New Jersey,United States

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