Pharmacokinetics and Pharmacodynamics Study of SEG101 (Crizanlizumab) in Sickle Cell Disease (SCD) Patients With Vaso- Occlusive Crisis (VOC)
Purpose
The purpose of the CSEG101A2202 study is 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 is designed as a Phase II, multicenter, open-label study. The first 45 patients (to identify 27 evaluable patients) will be 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 will also be collected prior to each dose. In addition, throughout the study (and when possible), all patients will have 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 are enrolled, 10 additional patients will be enrolled to the exploratory treatment group and begin at 7.5 mg/kg of crizanlizumab.
Condition
- Sickle Cell Disease
Eligibility
- Eligible Ages
- Between 16 Years and 70 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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
Other protocol-defined Inclusion/Exclusion criteria may apply.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental crizanlizumab 5 mg/kg |
SEG101 (crizanlizumab) drug at a dose of 5.0 mg/kg (or 7.5 mg/kg for exploratory group) by IV infusion. |
|
Recruiting Locations
Bronx, New York 10467
More Details
- NCT ID
- NCT03264989
- Status
- Recruiting
- Sponsor
- Novartis Pharmaceuticals