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
Interventions
Trade Name: Adakveo
Product Name: crizanlizumab
Product Code: SEG101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CRIZANLIZUMAB
Current Sponsor code: SEG101
Concentr
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent must be obtained prior to any screening procedures 2. Male or female patients aged 12 years and older on the day of signing informed consent. Adolescent include patients aged 12 to 17 years old and adults = 18 years 3. Confirmed diagnosis of SCD by hemoglobin electrophoresis or high performance liquid chromatography (HPLC) [performed locally]. All SCD genotypes are eligible, genotyping is not required for study entry 4a. Experienced at least 2 VOCs leading to healthcare visit within the 12 months prior to screening visit as determined by medical history. Prior VOC leading to healthcare visit must resolve at least 7 days prior to Week 1 Day 1 and must include: a. Pain crisis defined as an acute onset of pain for which there is no other medically determined explanation other than vaso- occlusion - b. a visit to a medical facility and/or healthcare professional, c. and receipt of oral/parenteral opioids or parenteral nonsteroidal anti-inflammatory drug (NSAID) analgesics Acute chest syndrome (ACS), priapism, and hepatic or splenic sequestration will be considered VOC in this study 5. If receiving HU/HC or L-glutamine (local HA approved medicinal product), must have been receiving the drug for at least 6 months and at a stable dose for at least 3 months prior to Screening visit and plan to continue taking at the same dose and schedule until the participants has reached one year of study treatment 6. Patients must meet the following central laboratory values prior to Week 1 Day 1. In case of re-sampling needed, local laboratory values are allowed. Refer to Section 8.4.1 for further details: • Absolute Neutrophil Count =1.0 x 109/L • Platelet count =75 x 109/L • Hemoglobin: for adults (Hb) =4.0 g/dL and for adolescents (Hb) =5.5 g/dL • Glomerular filtration rate = 45 mL/min/1.73 m2 using CKD-EPI formula in adults, and Shwartz formula in adolescents • Direct (conjugated) bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1. History of stem cell transplant. 2. Participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) and/or planning on undergoing an exchange transfusion during the duration of the study; episodic transfusion in response to worsened anemia or VOC is permitted. 3. Contraindication or hypersensitivity to any drug or metabolites 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. 4. Received active treatment on another investigational trial within 30 days (or 5 half-lives of that agent, whichever is greater) prior to Screening visit or plans to participate in another investigational drug trial. 5. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant unless they are using highly effective methods of contraception during dosing and for 15 weeks after stopping treatment. 6. Concurrent severe and/or uncontrolled medical conditions which, in the opinion of the Investigator, could cause unacceptable safety risks or compromise participation in the study. 7. History or current diagnosis of ECG abnormalities indicating significant risk of safety such as: • Concomitant clinically significant cardiac arrhythmias (e.g ventricular tachycardia), and clinically significant second or third degree AV block without a pacemaker • History of familial long QT syndrome or know family history of Torsades de Pointes 8. Not able to understand and to comply with study intructions and requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To compare the efficacy of 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOC leading to healthcare visit, in addition to standard of care - To compare the efficacy of 5.0 mg/kg of crizanlizumab versus placebo on the annualized rate of VOC leading to healthcare visit, in addition to standard of care;Secondary Objective: Key secondary: -To compare the efficacy of 7.5 mg/kg vs placebo on the annualized rate of all VOCs(managed at home+leading to healthcare visit) -To compare the efficacy of 5.0 mg/kg vs placebo on the annualized rate of all VOC(managed at home+leading to healthcare visit) -Assess the time to first &second VOC leading to healthcare visit in each group -Assess the annualized rate of VOCs managed at home in each group -Assess the duration of VOCs leading to healthcare visit in each group -Assess rate of participants free from VOC leading to healthcare visit in each group -Healthcare resource utilization(visits to clinic,Emergency room(ER)& hospitalizations)in each group vs placebo -To assess SCD-related renal damage in eachgroup -To characterize PK profile of crizanlizumab at 5.0 &7.5 mg/kg -To characterize PD(P-selectin inhibition) of crizanlizumab at 5.0 &7.5 mg/kg -To assess efficacy,safety and immunogenicity of crizanlizumab over the study period(treatment of 5y+105d follow-up);Primary end point(s): Annualized rate of VOC events leading to healthcare visit in each treatment group over the first year post-randomization;Timepoint(s) of evaluation of this end point: 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): for key secondary: - Annualized rate of all VOCs leading to healthcare visit and treated at home (based on documentation by health care provider following contact with participant) over the first year post randomization - The time to first and second VOC calculated respectively as the time from date of randomization until the first and the second VOC leading to healthcare visit over the first year post randomization - Annualized rate of VOCs managed at home over the first year post randomization - Duration of VOCs leading to healthcare visit over the first year post randomization - Number and percentage of participants free from VOCs leading to healthcare visit in each group over the first year post randomization - Annualized rate of visits to clinic, Emergency room (ER) and hospitalizations, both overall and VOCrelated over the first year post randomization - Evolution of albuminuria and ACR over the first year post randomization - PK parameters after the first and fifth dose (e.g., AUC, Cmax, Tmax, half-life) - PD parameter (P-selectin inhibition) after the first and fifth dose - Annualized rate of VOCs leading to healthcare visit - annualized rate of all VOCs leading to healthcare visit and treated at home - Annualized rate of VOCs managed at home -Number, seriousness, severity, and causality assessments of treatment-emergent adverse events, including infections (serious, non-serious and opportunistic infections) and other safety data as considered appropriate Absolute change from baseline in hemoglobin Growth and sexual maturity assessment in adolescents (Tanner stage) Immunogenicity: measurement of anti-drug antibodies (ADA) to crizanlizumab;Timepoint(s) of evaluation of this end point: 1 year - 1 year - 1 year - 5 years - 5 years - 5 years - 5 years - 5 years - 5 years - 5 years - 5 years | — |
Countries
Belgium, Brazil, Canada, Colombia, Egypt, Finland, France, Germany, Ghana, Greece, India, Italy, Jordan, Kenya, Lebanon, Netherlands, Oman, Panama, Saudi Arabia, South Africa, Spain, Turkey, United Arab Emirates, United Kingdom, United States
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed