Phase 2 Completed N=57 Treatment

Pharmacokinetics and Pharmacodynamics Study of SEG101 (Crizanlizumab) in Sickle Cell Disease (SCD) Patients With Vaso- Occlusive Crisis (VOC)

Sickle Cell Disease (SCD)

Source: ClinicalTrials.gov NCT03264989 ↗

Enrolled (actual)

Serious AEs

49.1%

Results posted

Apr 2024

Primary outcomePrimary: Pharmacokinetic (PK): AUCd15 and AUCtau of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients — 13100; 20800 hr*μg/mL

Summary

The purpose of the CSEG101A2202 study was to characterize the Pharmacokinetic (PK) and Pharmacodynamic (PD) of SEG101/crizanlizumab and to evaluate the safety and efficacy of SEG101/crizanlizumab in sickle cell disease (SCD) patients.

Outcome Measures

Outcome	Result	p-value
PRIMARY Pharmacokinetic (PK): AUCd15 and AUCtau of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients	13100; 20800	—
PRIMARY PK: Cmax of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients	102; 123	—
PRIMARY Pre-dose Concentrations Prior to Each Study Drug Dose	18.0; 10.8; 9.04; 10.0; 9.37; 9.91	—
PRIMARY Percentage of P-selectin Inhibition After the Starting Dose (PD-AUCd15), After Multiple Doses (PD-AUCd29) of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients	33200; 66900	—
PRIMARY Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients	97.3; 93.0; 87.8; 94.1; 91.7; 93.2	—
SECONDARY Annualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic/Emergency Room (ER)/Hospital	4.00; 2.00; 2.75; 0.97	—
SECONDARY Annualized Rate of VOC Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With Patient)	0.68; 0.71	—
SECONDARY Annualized Rate of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits	3.42; 2.47; 3.34; 0.86; 2.46; 1.44	—
SECONDARY Annualized Days of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits	11.95; 3.17; 9.03; 1.57; 10.31; 2.57	—
SECONDARY Annualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs))	0.00; 0.00; 0.62; 0.25; 1.00; 1.58	—
SECONDARY Annualized Rate of VOC Events (Including Both Healthcare Visit and Home Treatment)	3.42; 1.65	—
SECONDARY Number of Participants With Immunogenicity (IG) by Any Positive Status	0; 0; 0; 0; 0; 0	—

Eligibility Criteria

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03264989). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.