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

Study point of contact

Novartis Pharmaceuticals
+41613241111
Novartis Pharmaceuticals
1-888-669-6682
[email protected]

Locations

19 United States sites

5 Spain sites

4 Belgium sites

3 Brazil sites

3 Colombia sites

3 India sites

3 Italy sites

2 Canada sites

2 Germany sites

2 Lebanon sites

2 Turkey sites

2 United Kingdom sites

1 Oman site

1 Switzerland site

1 France site

Age

6 to 17 Years

Genotypes

HbSS, HbSC

Phase

Phase 2

Study type

Interventional

Gender

All

Interventions

Drug

Compensation

Unknown

About the study

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.

participation requirements

1. 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). 2. 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. 3. 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 4. 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. 5. Received standard age-appropriate care for SCD, including penicillin prophylaxis, pneumococcal immunization, and parental education. 6. Performance status: Karnofsky ≥ 50% for patients >10 years of age, and Lansky ≥ 50 for
patients ≤ 10 years of age.

7. 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

8. 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,

9. 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 10. 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. 11. 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.

participation restrictions

1. History of stem cell transplant.

2. Received any blood products within 30 days prior to Week 1 Day 1 dosing.

3. 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.

4. 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.

Locations

  • Birmingham, Alabama, United States, University of Alabama 1600 7th ave, 35233 [Recruiting]
  • Phoenix, Arizona, United States, Phoenix Childrens Hospital CVAL489A2302, 85016 [Recruiting]
  • Sacramento, California, United States, UC Davis Medical Center, 95817 [Recruiting]
  • Washington, District of Columbia, United States, Children s National Hospital, 20010 [Recruiting]
  • Gainesville, Florida, United States, University of Florida College of Medicine, 32610 [Recruiting]
  • Hollywood, Florida, United States, Joe DiMaggio Childrens Hospital, 33021 [Recruiting]
  • Atlanta, Georgia, United States, Childrens Healthcare of Atlanta, 30342 [Recruiting]
  • Chicago, Illinois, United States, Ann and Robert H Lurie Childrens Hospital of Chicago CTBM100C2407, 60611 [Recruiting]
  • Chicago, Illinois, United States, University of Chicago Hospital, 60637 [Recruiting]
  • Boston, Massachusetts, United States, Childrens Hospital Boston, 02115 [Recruiting]
  • Hackensack, New Jersey, United States, Institute for Pediatric Cancer and Blood Disorders, 07601 [Recruiting]
  • New Brunswick, New Jersey, United States, UMDNJ, 08901 [Recruiting]
  • Bronx, New York, United States, Children's Hospital at Montefiore, 10467 [Recruiting]
  • Durham, North Carolina, United States, Duke University Medical Center Oncology, 27710 [Recruiting]
  • Greenville, North Carolina, United States, East Carolina University SC, 27834 [Recruiting]
  • Philadelphia, Pennsylvania, United States, Childrens Hospital of Philadelphia, 19104 4399 [Recruiting]
  • Charleston, South Carolina, United States, Medical University of South Carolina Medical Uni of South Carolina, 29425 [Recruiting]
  • Memphis, Tennessee, United States, St. Jude Children's Research Hosptial, 38105 [Recruiting]
  • Fort Worth, Texas, United States, Cook Childrens Medical Center Oncology, 76104 [Recruiting]
  • Edegem, Antwerpen, Belgium, Novartis Investigative Site, 2650 [Recruiting]
  • Brussel, Belgium, Novartis Investigative Site, 1000 [Recruiting]
  • Laeken, Belgium, Novartis Investigative Site, 1020 [Recruiting]
  • Liege, Belgium, Novartis Investigative Site, 4000 [Recruiting]
  • Salvador, BA, Brazil, Novartis Investigative Site, 41253-190 [Recruiting]
  • Ribeirao Preto, SP, Brazil, Novartis Investigative Site, 14048-900 [Recruiting]
  • São Paulo, SP, Brazil, Novartis Investigative Site, 01232-010 [Recruiting]
  • Toronto, Ontario, Canada, Novartis Investigative Site, M5G 1X8 [Recruiting]
  • Montreal, Quebec, Canada, Novartis Investigative Site, H3T 1C5 [Recruiting]
  • Medellin, Antioquia, Colombia, Novartis Investigative Site, 05001000 [Recruiting]
  • Cali, Valle Del Cauca, Colombia, Novartis Investigative Site [Recruiting]
  • Monteria, Colombia, Novartis Investigative Site [Recruiting]
  • Paris cedex 15, France, Novartis Investigative Site, 75015 [Recruiting]
  • Heidelberg, Baden Wuerttemberg, Germany, Novartis Investigative Site, 69120 [Recruiting]
  • Berlin, Germany, Novartis Investigative Site, 13353 [Recruiting]
  • Nagpur, Maharashtra, India, Novartis Investigative Site, 440009 [Recruiting]
  • New Delhi, India, Novartis Investigative Site, 110029 [Recruiting]
  • Vellore, India, Novartis Investigative Site [Recruiting]
  • Modena, Italy, Novartis Investigative Site, 41124 [Recruiting]
  • Orbassano, Italy, Novartis Investigative Site, 10043 [Recruiting]
  • Padova, Italy, Novartis Investigative Site, 35128 [Recruiting]
  • Beirut, Lebanon, Novartis Investigative Site, 1107 2020 [Recruiting]
  • Tripoli, Lebanon, Novartis Investigative Site, 1434 [Recruiting]
  • Muscat, Oman, Novartis Investigative Site, 123 [Recruiting]
  • Esplugues de Llobregat, Barcelona, Spain, Novartis Investigative Site, 08950 [Recruiting]
  • Barcelona, Catalunya, Spain, Novartis Investigative Site, 08035 [Recruiting]
  • Valencia, Comunidad Valenciana, Spain, Novartis Investigative Site, 46026 [Recruiting]
  • Palma De Mallorca, Islas Baleares, Spain, Novartis Investigative Site, 07120 [Recruiting]
  • Madrid, Spain, Novartis Investigative Site, 28007 [Recruiting]
  • Aarau, Aargau, Switzerland, Novartis Investigative Site, 5001 [Recruiting]
  • Adana, Turkey, Novartis Investigative Site, 01330 [Recruiting]
  • Mersin, Turkey, Novartis Investigative Site, 33343 [Recruiting]
  • London, United Kingdom, Novartis Investigative Site, SE1 7EH [Recruiting]
  • London, United Kingdom, Novartis Investigative Site, SE5 8AD [Recruiting]