Sickle Cell Disease with Vaso-Occlusive Crisis MedDRA version: 21.0 Level: PT Classification code 10040644 Term: Sickle cell disease System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.1 Level: LLT Classification code 10002077 Term: Anaemia sickle cell System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Male or female patients aged 2 to 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 (eGFRe) = 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 =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
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 while on study, other than 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To confirm and establish appropriate dosing of crizanlizumab in patients ages 6 months to <18 years at the time of study entry (Part A and B) - To evaluate the safety of crizanlizumab in patients ages 6 months to <18 years at the time of study entry (Parts A and B);Secondary Objective: - To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old patients at the time of study entry (Parts A and B) - To assess other safety measures in patients aged 6 months to < 18 years at the time of study entry - To characterize long-term PK and PD of crizanlizumab in patients ages 6 months to <18 years at the time of study entry;Primary end point(s): 1.PK (AUCd15) after 1st dose Confirm appropriate dosing of crizanlizumab in participants aged 2 to < 18 years (Parts A) 2.PD (AUCd15) after 1st dose Confirm appropriate dosing of crizanlizumab in participants aged 2 to < 18 years (Parts A) 3.PK (AUCtau) after multiple dose Confirm appropriate dosing of Crizanlizumab in participants aged 2 to < 18 years old 4.PD (AUCtau) after multiple dose Confirm appropriate dosing of Crizanlizumab in participants aged 2 to < 18 years old 5.PK (Cmax) after 1st dose and multiple dose Confirm appropriate dosing of crizanlizumab in participants aged 2 to < 18 years (Parts A) 6.PK pre-dose concentrations Confirm appropriate dosing of crizanlizumab in participants aged 6 months to less than 24 months of age (Part B) 7.Frequency of any adverse events (AEs) as a measure of safety and tolerability Safety of crizanlizumab in participants aged 6 months to < 18 years (Parts A and B);Timepoint(s) of evaluation of this end point: 1. Day 15 2. Day 15 3. Week 15 4. Week 15 5. Week 1 and Week 15 6. Week 1 and Week 19 7. 6 months, 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Annualized rate Vaso Occusive Crisis (VOC) events leading to healthcare visit in clinic/ER/hospital To assess the long-term efficacy of crizanlizumab in 6 months to 18 years 13.PD pre-dose concentrations prior to each study drug dose. Characterize long-term PK and PD of crizanlizumab in participants aged 6 months to >18 years 14.Percentage P-selectin inhibition prior to dosing Characterize long-term PK and PD of crizanlizumab in participants aged 6months to >18 years;Timepoint(s) of evaluation of this end point: 1. 6 months, 2 years 2. 6 months, 2 years 3. 6 months, 2 years 4. 6 months, 2 years 5. 6 months, 2 years 6. 6 months, 2 years 7. 6 months, 2 years 8. 6 months, 2 years 9. Week 1, Week 3, Week 15, Week 27 and End of Treatment (EOT) 10. Screening, Week 7, Week 11, week 15, week 27 and Week 51 11. Screening, Week 51 and End of Treatment (EOT) 12. Week 1, Week 3, Week 7, Week 15, Week 19, Week 23, Week 27, Week 31, Week 35, Week 39, Week 43, Week 47 and Week 51 13. Week 1, Week 3, Week 7, Week 15, Week 19, Week 23, Week 27, Week 31, Week 35, Week 39, Week 43, Week 47 and Week 51 14. Week 3, Week 15, Week 27 and Week 51 | — |
Countries
Belgium, Brazil, Canada, Colombia, France, Germany, India, Italy, Lebanon, Oman, Spain, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactMedical Information Services
Novartis Pharmaceuticals UK Limited
Outcome results
None listed