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

Novartis

Status and phase

Completed

Phase 2

Conditions

Sickle Cell Disease (SCD)

Treatments

Drug: crizanlizumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT03264989

CSEG101A2202

Details and patient eligibility

About

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.

Full description

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 Pharmacokinetic/Pharmacodynamic (PK/PD) sampling at week 1 and week 15. In all patients, trough PK/PD samples were 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 began at 7.5 mg/kg of crizanlizumab.

The study was initiated on 19-Dec-2017. This study provides five years follow up data that fully characterizes the safety, tolerability and treatment effect of the 5.0 mg/kg and 7.5 mg/kg doses of crizanlizumab along with the initially planned PK and PD data.

At the time of study closure, crizanlizumab 5.0 mg/kg was an FDA approved treatment in the United States (US) for patients with sickle-cell disease. Therefore, the patients treated with crizanlizumab 5.0 mg/kg dose were encouraged to transition to commercial supply of crizanlizumab. The patients treated with the not currently approved dose of crizanlizumab 7.5 mg/kg were allowed to join a multi-center, multi-national, rollover clinical trial (Study SEG101A2401B), for continued access to treatment with crizanlizumab.

Enrollment

57 patients

Sex

All

Ages

16 to 70 years old

Volunteers

No Healthy Volunteers

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