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

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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
Enrollment count 
100 participants
Start date 
Oct 01, 2018
Completion date 
Nov 20, 2024
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 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 excluded.

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 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
United States
Phoenix Childrens Hospital CVAL489A2302
Recruiting
Phoenix, 85016
Arizona
United States
UC Davis Medical Center
Recruiting
Sacramento, 95817
California
United States
Children s National Hospital
Recruiting
Washington, 20010
District of Columbia
United States
University of Florida College of Medicine
Recruiting
Gainesville, 32610
Florida
United States
Joe DiMaggio Childrens Hospital
Recruiting
Hollywood, 33021
Florida
United States
Childrens Healthcare of Atlanta
Recruiting
Atlanta, 30342
Georgia
United States
Ann and Robert H Lurie Childrens Hospital of Chicago CTBM100C2407
Recruiting
Chicago, 60611
Illinois
United States
University of Chicago Hospital
Recruiting
Chicago, 60637
Illinois
United States
Childrens Hospital Boston
Recruiting
Boston, 02115
Massachusetts
United States
Institute for Pediatric Cancer and Blood Disorders
Recruiting
Hackensack, 07601
New Jersey
United States
UMDNJ
Recruiting
New Brunswick, 08901
New Jersey
United States
Children's Hospital at Montefiore
Recruiting
Bronx, 10467
New York
United States
Duke University Medical Center Oncology
Recruiting
Durham, 27710
North Carolina
United States
East Carolina University SC
Recruiting
Greenville, 27834
North Carolina
United States
Childrens Hospital of Philadelphia
Recruiting
Philadelphia, 19104 4399
Pennsylvania
United States
Medical University of South Carolina Medical Uni of South Carolina
Recruiting
Charleston, 29425
South Carolina
United States
St. Jude Children's Research Hosptial
Recruiting
Memphis, 38105
Tennessee
United States
Cook Childrens Medical Center Oncology
Recruiting
Fort Worth, 76104
Texas
United States
Belgium
Novartis Investigative Site
Recruiting
Edegem, 2650
Antwerpen
Belgium
Novartis Investigative Site
Recruiting
Brussel, 1000
-
Belgium
Novartis Investigative Site
Recruiting
Laeken, 1020
-
Belgium
Novartis Investigative Site
Recruiting
Liege, 4000
-
Belgium
Brazil
Novartis Investigative Site
Recruiting
Salvador, 41253-190
BA
Brazil
Novartis Investigative Site
Recruiting
Ribeirao Preto, 14048-900
SP
Brazil
Canada
Novartis Investigative Site
Recruiting
Montreal, H3T 1C5
Quebec
Canada
Colombia
Novartis Investigative Site
Recruiting
Medellin, 05001000
Antioquia
Colombia
Novartis Investigative Site
Recruiting
Cali,
Valle Del Cauca
Colombia
Novartis Investigative Site
Recruiting
Monteria,
-
Colombia
France
Novartis Investigative Site
Recruiting
Paris cedex 15, 75015
-
France
Germany
Novartis Investigative Site
Recruiting
Heidelberg, 69120
Baden Wuerttemberg
Germany
Novartis Investigative Site
Recruiting
Berlin, 13353
-
Germany
India
Novartis Investigative Site
Recruiting
Nagpur, 440009
Maharashtra
India
Novartis Investigative Site
Recruiting
New Delhi, 110029
-
India
Novartis Investigative Site
Recruiting
Vellore,
-
India
Italy
Novartis Investigative Site
Recruiting
Modena, 41124
-
Italy
Novartis Investigative Site
Recruiting
Orbassano, 10043
-
Italy
Novartis Investigative Site
Recruiting
Padova, 35128
-
Italy
Lebanon
Novartis Investigative Site
Recruiting
Beirut, 1107 2020
-
Lebanon
Novartis Investigative Site
Recruiting
Tripoli, 1434
-
Lebanon
Oman
Novartis Investigative Site
Recruiting
Muscat, 123
-
Oman
Spain
Novartis Investigative Site
Recruiting
Esplugues de Llobregat, 08950
Barcelona
Spain
Novartis Investigative Site
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
Novartis Investigative Site
Recruiting
Madrid, 28007
-
Spain
Switzerland
Novartis Investigative Site
Recruiting
Aarau, 5001
Aargau
Switzerland
Turkey
Novartis Investigative Site
Recruiting
Adana, 01330
-
Turkey
Novartis Investigative Site
Recruiting
Mersin, 33343
-
Turkey
United Kingdom
Novartis Investigative Site
Recruiting
London, SE5 8AD
-
United Kingdom

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

Have a question?

Call 1-999-669-6682 or email [email protected]