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

  • STATUS
    Recruiting
  • End date
    Dec 17, 2025
  • participants needed
    100
  • sponsor
    Novartis Pharmaceuticals
Updated on 24 May 2022
opioid
stroke
absolute neutrophil count
glutamine
conjugated bilirubin
electrophoresis
thalassemia
sickle hemoglobin

Summary

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.

Details
Condition Sickle Cell Disease (SCD)
Treatment crizanlizumab
Clinical Study IdentifierNCT03474965
SponsorNovartis Pharmaceuticals
Last Modified on24 May 2022

Eligibility

Yes No Not Sure

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](telnet://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](telnet://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
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
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
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
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
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
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)
Sexually active females who are unwilling to comply with reliable method of birth
control until 15 weeks following last dose of study drug
Not able to understand and to comply with study instructions and requirements
Patients who are an employee of the sponsor or investigator or otherwise dependent on
them
Patients who are committed to an institution by virtue of an order issued either by the
judicial or the administrative authorities
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
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