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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03264989

Collaborator

(none)

Enrollment

Locations

Arm

66.3

Anticipated Duration (Months)

4.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease (SCD)	Drug: crizanlizumab	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

57 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Multicenter, Open-Label Study to Assess PK/PD of SEG101 (Crizanlizumab), With or Without Hydroxyurea/Hydroxycarbamide, in Sickle Cell Patients With Vaso-Occlusive Crisis

Actual Study Start Date :

Dec 19, 2017

Anticipated Primary Completion Date :

Mar 17, 2023

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: crizanlizumab SEG101 (crizanlizumab) drug at a dose of 5.0 mg/kg (or 7.5 mg/kg for exploratory group) by IV infusion Other Names: SEG101

Arm

Intervention/Treatment

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.

Drug: crizanlizumab

SEG101 (crizanlizumab) drug at a dose of 5.0 mg/kg (or 7.5 mg/kg for exploratory group) by IV infusion

Other Names:

SEG101

Outcome Measures

Primary Outcome Measures

To characterize PK (AUC) of crizanlizumab at 5.0 mg/kg in SCD patients. [Week1 Day 1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr; 72hr; Week2 Day 1; Week3 Day 1; Week15 Day1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr; 72hr; Week16 Day1; Week17 Day1; Week18 Day1; Week19 Day1]
PK (AUC)
To characterize PK (Ctrough) of crizanlizumab at 5.0 mg/kg in SCD patients. [Week 1 Day1; Week3 Day1; Week7 Day1; Week11 Day1; Week15 Day1; Week19 Day1; Week23 Day1; Week27 Day1; Week31 Day1; Week35 Day1; Week39 Day1; Week43 Day1; Week47 Day1; Week51 Day1, W75 Day1, W99 Day 1, W123 Day 1, W147 Day 1, W171 Day 1, Safety FU]
PK (Ctrough)
To characterize PK (Cmax) of crizanlizumab at 5.0 mg/kg in SCD patients. [Week1 Day1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr; Week15 Day1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr]
PK (Cmax)
Pharmacodynamics (PD): Percentage of P-selectin inhibition and PD-AUC inhibition of crizanlizumab at 5.0 mg/kg in SCD patients [Week1 Day1 Pre-dose, 2hr, 24hr; 72hr; Week2 Day1; Week3 Day1; Week15 Day1 Pre-dose, 2hr, 24hr; 72hr; Week16 Day1; Week17 Day1; Week18 Day1; Week19 Day1]
P-selectin inhibition percentage & PD AUC inhibition after the starting dose, after multiple doses and prior to each study drug dose

Secondary Outcome Measures

Annualized rate of VOC events leading to healthcare visit in clinic/ER/hospital over time. [Week 1 through end of treatment (approximately 24 months)]
Assess efficacy of crizanlizumab (VOC leading to healthcare visits)
Annualized rate of VOC events treated at home (based on documentation by health care provider following phone contact with patient) over time. [Week 1 through end of treatment (approximately 24 months)]
Assess efficacy of crizanlizumab (VOC treated at home)
Annualized rate of VOC events (including both healthcare visit and home treatment). [Week 1 through end of treatment (approximately 24 months)]
Assess efficacy of crizanlizumab (VOC events)
Annualized rate of each subcategory of all VOC events (uncomplicated pain crisis, acute chest syndrome, hepatic sequestration, splenic sequestration, priapism) over time. [Week 1 through end of treatment (approximately 24 months)]
Assess efficacy of crizanlizumab (subcategory of VOC events)
Annualized rate of hospitalizations and ER visits (both total and VOC-related) over time. [Week 1 through end of treatment (approximately 24 months)]
Assess efficacy of crizanlizumab (hospitalizations and ER visits)
Annualized days of ER/hospitalization (both total and VOC-related) over time. [Week 1 through end of treatment (approximately 24 months)]
Assess efficacy of crizanlizumab (Days of ER/hospitalizations)

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 70 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mid Florida Hematology and Oncology Center	Orange City	Florida	United States	32763
2	Tampa General Hospital	Tampa	Florida	United States	33606
3	Childrens Healthcare of Atlanta	Atlanta	Georgia	United States	30342
4	Augusta University Georgia Cancer Center Pharmacy Patient Treatment	Augusta	Georgia	United States	30912
5	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
6	Children's Hospital at Montefiore	Bronx	New York	United States	10467
7	Duke University Medical Center Patient Treatment	Durham	North Carolina	United States	27710
8	East Carolina University East Carolina University	Greenville	North Carolina	United States	27858
9	Children s Hospital of Philadelphia Patient Treatment	Philadelphia	Pennsylvania	United States	19104-4399
10	Medical University of South Carolina Medical Univ of SC	Charleston	South Carolina	United States	29425
11	M Francisco Gonzalez MD PA	Columbia	South Carolina	United States	29203
12	Carolina Blood and Cancer Care of South Carolina	Rock Hill	South Carolina	United States	29732