| Protocol No: | ECCT/20/07/03 | Date of Protocol: | 02-06-2020 |
| Study Title: | A Phase III multicenter, randomized, double blind study to assess efficacy and safety of two doses of crizanlizumab verses placebo, with or without hydroxyurea/hydroxycarbamide therapy in adolescent and adult sickle cell disease patients with Vaso-Occlusive Crises (STAND) |
| Study Objectives: | Primary 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 •To assess the time to first and second VOC leading to healthcare visit in each group •To assess rate of subjects free from VOC leading to healthcare visit in each group •To assess the number of days with VOC leading to healthcare visit in each group •Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) in each group •To assess SCD-related renal damage in each group •To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg •To characterize the pharmacodynamic (PD) (P-selectin inhibition) of crizanlizumab at 5.0 and 7.5 mg/kg •To assess efficacy, safety and immunogenicity of crizanlizumab over the study period (taking into account potential treatment switch after primary analysis) |
| Laymans Summary: | A study of two doses of crizanlizumab versus placebo in adolescent and adult sickle cell disease patients with vaso-occlusive crises |
| Abstract of Study: | Pre-clinical data have established P-selectin as a key mediator of vaso-occlusion in SCD and suggest that its blockade could eliminate or reduce VOCs The A2210 study (SUSTAIN) compared the mean trough percentage P-selectin inhibition obtained with crizanlizumab following administration of 2.5mg/kg dose and 5.0mg/kg dose and suggested that the degree of clinical benefit may be correlated with achieving a certain level of P-selectin inhibition. Since trough concentration is highly correlated with % P-selectin inhibition 7.5mg/kg is the proposed dose to achieve higher percentage P-selectin inhibition in SCD patients The purpose of this study is to compare the efficacy and safety of two doses of crizanlizumab 5mg/kg and 7.5mg/kg verses placebo in adolescent and adult SCD patients with history of VOC leading to healthcare visit |