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

Phase 1

Conditions: Sickle Cell Disease with Vaso-Occlusive Crisis
MedDRA version: 21.0Level: PTClassification code 10040644Term: Sickle cell diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 20.1Level: LLTClassification code 10002077Term: Anaemia sickle cellSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2017-001747-12-BE

Lead Sponsor: ovartis Pharma AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 100

Inclusion Criteria

•Male or female patients aged 2 to <18 years
•Confirmed diagnosis of sickle cell disease (SCD) (e.g. any genotype
including HbSS, HbSC, HbSß0-thalassemia, HbSß+-thalassemia, and
others) by hemoglobin electrophoresis and/or 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:
1.the occurrence of appropriate symptoms (see VOC definition in
protocol Section 7.2.1.1)
2.either a visit to a medical facility or healthcare professional,
3.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, HbSß0-thalassemia, and HbSD disease indicating
low risk for stroke (per investigator). Please refer to Section 7.2.2.6 for
details.
Other inclusion criteria as per protocol may apply
Are the trial subjects under 18? yes
Number of subjects for this age range: 100
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

•History of stem cell transplant.
•Received any blood products within 30 days prior to Day 1 dosing.
•Plan to participate in a chronic transfusion program (preplanned 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.
•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)
•Significant active infection or immune deficiency (including chronic use of immunosuppressive drugs) in the opinion of the investigator.
•Patients having taken voxelotor less than 30 days prior to Screening, or planning to take voxelotor while on study are not allowed
Other exclusion criteria as per protocol may apply