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

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: NCT03474965

Novartis Reference Number: CSEG101B2201

Last Update: Jul 26, 2022

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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.

Condition 
Sickle Cell Disease (SCD)
Phase 
Phase 2
Overall status 
Recruiting
Start date 
Oct 01, 2018
Completion date 
Dec 17, 2025
Gender 
All
Age(s)
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 Locations

United States
University of Alabama 1600 7th ave
Recruiting
Birmingham, 35233 - Alabama
Contact: Christy Patrick (205-638-9285) - [email protected] - Thomas Howard
United States
Phoenix Childrens Hospital CVAL489A2302
Recruiting
Phoenix, 85016 - Arizona
Contact: Courtney Moyer (602-546-4702) - [email protected] - Sanjay Shah
United States
UC Davis Medical Center
Recruiting
Sacramento, 95817 - California
Contact: Michelle Adams (916-734-2011) - [email protected] - Jo Chung
United States
Childrens National Hospital
Recruiting
Washington, 20010 - District of Columbia
Contact: Stefanie Jesus Margulies (+1 202 476 5000) - [email protected] - Andrew Campbell
United States
University of Florida College of Medicine
Recruiting
Gainesville, 32610 - Florida
Contact: Melissa Lingis (353-273-9120) - [email protected] - John Fort
United States
Joe DiMaggio Childrens Hospital
Recruiting
Hollywood, 33021 - Florida
Contact: Nathalie Espinosa (954-265-5324) - [email protected] - Anne Schaefer
United States
Childrens Healthcare of Atlanta
Recruiting
Atlanta, 30342 - Georgia
Contact: Octavia Geter-Fuller - [email protected] - Robert Clark Brown
United States
Ann and Robert H Lurie Childrens Hospital of Chicago
Recruiting
Chicago, 60611 - Illinois
Contact: Kayla Jones (+1 312 227 4811) - [email protected] - Astrid Kyle Mack
United States
University of Chicago Hospital
Recruiting
Chicago, 60637 - Illinois
Contact: Mariel Galvan (773-702-2084) - [email protected] - Radhika Peddinti
United States
Childrens Hospital Boston
Recruiting
Boston, 02115 - Massachusetts
Contact: Erika Tavares (617-355-7700) - [email protected] - Matthew M Heeney
United States
Childrens Hospital of Michigan
Recruiting
Detroit, 48201 - Michigan
Contact: Charmaine Williams Farr (313-645-5515) - [email protected] - Sharada Sarnaik
United States
Institute for Pediatric Cancer and Blood Disorders
Recruiting
Hackensack, 07601 - New Jersey
Contact: Elana Smilow (551-996-5437) - [email protected] - Stacey Rifkin-Zenenberg
United States
UMDNJ
Recruiting
New Brunswick, 08901 - New Jersey
Contact: Sherri Gzemski - [email protected] - Richard DRACHTMAN
United States
Children's Hospital at Montefiore
Recruiting
Bronx, 10467 - New York
Contact: Jill Fillipelli (718-741-2384) - [email protected] - Deepa Manwani
United States
Duke University Medical Center Oncology
Recruiting
Durham, 27710 - North Carolina
Contact: Patrick Barrera (919-684-1018) - [email protected] - Jennifer Rothman
United States
East Carolina University SC
Recruiting
Greenville, 27834 - North Carolina
Contact: Derrick Almond (252-744-4676) - [email protected] - Beng Fuh
United States
Children s Hospital of Philadelphia Patient Treatment
Recruiting
Philadelphia, 19104-4399 - Pennsylvania
Contact: Julia Sabrick (267-426-9338) - [email protected] - Helge D Hartung
United States
Medical University of South Carolina Medical Uni of South Carolina
Recruiting
Charleston, 29425 - South Carolina
Contact: Kreighton M. Milks - [email protected] - Shayla Bergmann
United States
St. Jude Children's Research Hosptial
Recruiting
Memphis, 38105 - Tennessee
Contact: Olivia McGregor (901-595-7188) - [email protected] - Jeremie Heath Estepp
United States
Cook Childrens Medical Center Oncology
Recruiting
Fort Worth, 76104 - Texas
Contact: Patty Penn (682-885-1990) - [email protected] - Clarissa Johnson
United States
Texas Childrens Hospital CFTY720D2311
Recruiting
Houston, 77030 - Texas
Contact: Batha Tariq (832-822-1804) - [email protected] - Venee Tubman
United States
Belgium
Novartis Investigative Site
Recruiting
Edegem, 2650
Antwerpen
Belgium
Novartis Investigative Site
Recruiting
Brussel, 1000
-
Belgium
Novartis Investigative Site
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Laeken, 1020
-
Belgium
Novartis Investigative Site
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Liege, 4000
-
Belgium
Brazil
Novartis Investigative Site
Recruiting
Salvador, 41253-190
BA
Brazil
Novartis Investigative Site
Recruiting
Ribeirao Preto, 14048-900
SP
Brazil
Novartis Investigative Site
Recruiting
São Paulo, 01232-010
SP
Brazil
Canada
Novartis Investigative Site
Recruiting
Toronto, M5G 1X8
Ontario
Canada
Novartis Investigative Site
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Montreal, H3T 1C5
Quebec
Canada
Colombia
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Cali,
Valle Del Cauca
Colombia
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Monteria,
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Colombia
France
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Paris cedex 15, 75015
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France
Germany
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Heidelberg, 69120
Baden Wuerttemberg
Germany
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Berlin, 13353
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Germany
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Koeln, 50937
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Germany
India
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Maharashtra
India
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New Delhi, 110029
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India
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Vellore,
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India
Italy
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Modena, 41124
MO
Italy
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Padova, 35128
PD
Italy
Novartis Investigative Site
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Orbassano, 10043
TO
Italy
Lebanon
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Beirut, 1107 2020
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Lebanon
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Tripoli, 1434
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Lebanon
Oman
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Muscat, 123
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Oman
Spain
Novartis Investigative Site
Recruiting
Esplugues de Llobregat, 08950
Barcelona
Spain
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Recruiting
Barcelona, 08035
Catalunya
Spain
Novartis Investigative Site
Recruiting
Valencia, 46026
Comunidad Valenciana
Spain
Novartis Investigative Site
Recruiting
Palma De Mallorca, 07120
Islas Baleares
Spain
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Recruiting
Madrid, 28009
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Spain
Switzerland
Novartis Investigative Site
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Aarau, 5001
Aargau
Switzerland
Turkey
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Recruiting
Adana, 01330
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Turkey
Novartis Investigative Site
Recruiting
Mersin, 33343
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Turkey
United Kingdom
Novartis Investigative Site
Recruiting
London, SE1 7EH
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United Kingdom
Novartis Investigative Site
Recruiting
London, SE5 8AD
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United Kingdom
Novartis Investigative Site
Recruiting
Manchester, M13 9WL
-
United Kingdom

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