Health Condition 1: D758- Other specified diseases of bloodand blood-forming organs
Conditions
Interventions
Intervention1: Crizanlizumab(SEG101): 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
Sponsors
Novartis Healthcare Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male or female patients ages 2 to 2. Confirmed diagnosis of SCD (e.g. any genotype including HbSS, HbSC, HbSß0 thalassemia,HbSß+-thalassemia patients, others) by hemoglobin electrophoresis or highperformance liquid chromatography (HPLC) [performed locally]. 3. Experienced at least 1 VOC within the preceding 12 months, as determined by medical history. Prior VOC must have resolved at least 7 days prior to the first dose in the study and should 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 other non-opioid parenteral analgesia. 4. If receiving HU/HC or erythropoietin stimulating agent, must have been receiving the drug for at least 6 months prior to Screening and plan to continue taking at the same dose and schedule during the trial. 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 at the screening visit: ? 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 (eGFRe) = 45 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) considered low risk within the past 6 months (for ages 2 to 16 years). 10. Written informed consent/assent, according to local guidelines, signed by the patients 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
Exclusion criteria
Exclusion criteria: •History of stem cell transplant. •Received any blood products within 30 days of Day 1 dosing. •Participating and maintaining in a chronic transfusion program (preplanned series of transfusions for prophylactic purposes). •Patients with bleeding disorders •Planning on undergoing an exchange transfusion during the duration of the study. Patients requiring episodic transfusion in response to worsened anemia or VOC are permitted. •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 •Significant active infection or immune deficiency (including chronic use of immunosuppressive drugs) in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.PK (AUCd15) after 1st dose 2.PD (AUCd15) after 1st dose 3.PK (AUCtau) after 5th dose 4.PK (AUCtau) after 5th dose 5.PK (Cmax) after 1st dose and 5th dose 6.PK pre-dose concentrations 7.Frequency of any adverse events (AEs) as a measure of safety and tolerabilityTimepoint: 1.Time Frame: Day 15 2.Time Frame: Day 15 3.Time Frame: Week 15 4.Time Frame: Week 15 5.Time Frame: Week 1 and Week 15 6.Time Frame: Week 3 to Week 19 7.Time Frame: 6 months, 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| •Absolute change from baseline in hemoglobin To assess other safety measures in patients aged 6 months to 18 years at the time of study entryTimepoint: Baseline, 6 months, 2 years;•Electrocardiogram (ECGs) at relevant PK time points To assess other safety measures in patients aged 6 months to 18 years at the time of study entryTimepoint: Screening, Week 7, Week 11, week 15, week 27 and Week 51;•Growth and sexual maturation assessments (Tanner stage) To assess other safety measures in patients aged 6 months to 18 years at the time of study entryTimepoint: Screening, Week 51 and End of Treatment (EOT);•Immunogenicity: measurement of anti-drug antibodies (ADA) to crizanlizumab To assess other safety measures in patients aged 6 months to 18 years at the time of study entryTimepoint: Week 1, Week 3, Week 15, Week 27 and End of Treatment (EOT);•Number of dactylitis events 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)Timepoint: 6 months, 2 years;•Number of days of ER/hospitalization (both overall and VOC-related) 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)Timepoint: 6 months, 2 years;•Number of each subcategory of VOC event (uncomplicated pain crisis, acute chest syndrome, hepatic sequestration, splenic sequestration, priapism) 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)Timepoint: 6 months, 2 years;•Number of hospitalizations and ER visits (both overall and VOC-related) 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)Timepoint: 6 months, 2 years;•Number of 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 year old patients a | — |
Countries
Belgium, Brazil, Canada, Colombia, France, Germany, India, Italy, Lebanon, Oman, Spain, Switzerland, Turkey, United Kingdom, United States of America
Contacts
Public ContactMurugananthan K
Novartis Healthcare Private Limited
Outcome results
None listed