Pharmacokinetics and Pharmacodynamics Study of SEG101 (Crizanlizumab) in Sickle Cell Disease (SCD) Patients With Vaso- Occlusive Crisis (VOC)
Pharmacokinetics and Pharmacodynamics Study of SEG101 (Crizanlizumab) in Sickle Cell Disease (SCD) Patients With Vaso- Occlusive Crisis (VOC)
The purpose of the CSEG101A2202 study was to characterize the PK and PD of
 SEG101/crizanlizumab at 5 mg/kg and to evaluate the safety and efficacy of
 SEG101/crizanlizumab in SCD patients.

 Study CSEG101A2202 was designed as a Phase II, multicenter, open-label study. The first 45
 patients (to identify 27 evaluable patients) were enrolled to the treatment group
 crizanlizumab 5.0 mg/kg to complete full PK/PD sampling at week 1 and week 15. In all
 patients, trough PK/PD samples was collected prior to each dose. In addition, throughout the
 study (and when possible), all patients had blood drawn for serum to assess PK and PD drawn
 at times of onset and resolution of each VOC event, fever, or infection. Once the up to 45
 patients were enrolled, 12 additional patients were enrolled to the exploratory treatment
 group and begin at 7.5 mg/kg of crizanlizumab.
Inclusion Criteria:

 -  Male and non-pregnant female patients 16-70 years of age (inclusive)

 -  Confirmed diagnosis of sickle cell disease by hemoglobin electrophoresis or
 high-performance liquid chromatography (HPLC) [performed locally]. All sickle cell
 disease genotypes are eligible.

 -  Experienced at least 1 VOC within the preceding 12 months prior to Screening, as
 determined by medical history.

 -  If receiving HU/HC or erythropoietin stimulating agent, must have been receiving the
 drug for at least 6 months prior to Screening

 -  Hemoglobin ≥4.0 g/dL. Absolute neutrophil count ≥1.0 x 109/L and platelet count ≥75 x
 109/L

 -  Adequate renal and hepatic function as defined:

 -  GFR ≥45 mL/min/1.73 m2 calculated by CKD-EPI

 -  ALT ≤3 x ULN

 -  Direct (conjugated) bilirubin ≤2 x ULN

 -  ECOG performance status ≤2

 -  Written informed consent (or assent/ parental consent for minor subjects) prior to any
 screening procedures

 Exclusion Criteria:

 -  History of stem cell transplant.

 -  Acute VOC ending 7 days prior to first dosing

 -  Ongoing hospitalization prior to Screening

 -  Received blood products within 30 days to first dosing

 -  Participating in a chronic transfusion program (pre-planned series of transfusions for
 prophylactic purposes)

 -  History of severe hypersensitivity reactions to other monoclonal antibodies

 -  Received a monoclonal antibody or immunoglobulin -based agent within 1 year of
 Screening, or has documented immunogenicity to a prior biologic.

 -  Received active treatment on another investigational trial within 30 days (or 5
 half-lives of that agent, whichever is greater) prior to Screening

 -  Significant active infection or immune deficiency (including chronic use of
 immunosuppressive drugs)

 -  Resting QTcF ≥470 msec at pretreatment (baseline) or other cardiac or cardiac
 repolarization abnormality