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

Primary Purpose

Sickle Cell Disease (SCD)

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

crizanlizumab

About this trial

This is an interventional treatment trial for Sickle Cell Disease (SCD) focused on measuring Sickle cell disease, SCD, sickle cell anemia, vaso-occlusive crisis, P-selectin, SEG101, crizanlizumab, monoclonal antibody, Anemia, Sickle Cell, HbS Disease, Hemoglobin SC Disease, Sickle Cell Disorders, Sickling Disorder Due to Hemoglobin S

Eligibility Criteria

16 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept 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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

crizanlizumab 5 mg/kg

Arm Description

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

Outcomes

Primary Outcome Measures

To characterize PK (AUC) of crizanlizumab at 5.0 mg/kg in SCD patients.

PK (AUC)

To characterize PK (Ctrough) of crizanlizumab at 5.0 mg/kg in SCD patients.

PK (Ctrough)

To characterize PK (Cmax) of crizanlizumab at 5.0 mg/kg in SCD patients.

PK (Cmax)

Pharmacodynamics (PD): Percentage of P-selectin inhibition and PD-AUC inhibition of crizanlizumab at 5.0 mg/kg in SCD patients

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.

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.

Assess efficacy of crizanlizumab (VOC treated at home)

Annualized rate of VOC events (including both healthcare visit and home treatment).

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.

Assess efficacy of crizanlizumab (subcategory of VOC events)

Annualized rate of hospitalizations and ER visits (both total and VOC-related) over time.

Assess efficacy of crizanlizumab (hospitalizations and ER visits)

Annualized days of ER/hospitalization (both total and VOC-related) over time.

Assess efficacy of crizanlizumab (Days of ER/hospitalizations)

Full Information

NCT ID

NCT03264989

First Posted

August 4, 2017

Last Updated

September 18, 2023

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03264989

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Completed

Study Start Date

December 19, 2017 (Actual)

Primary Completion Date

June 26, 2023 (Actual)

Study Completion Date

June 26, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

Detailed 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sickle Cell Disease (SCD)

Keywords

Sickle cell disease, SCD, sickle cell anemia, vaso-occlusive crisis, P-selectin, SEG101, crizanlizumab, monoclonal antibody, Anemia, Sickle Cell, HbS Disease, Hemoglobin SC Disease, Sickle Cell Disorders, Sickling Disorder Due to Hemoglobin S

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

57 (Actual)

8. Arms, Groups, and Interventions

Arm Title

crizanlizumab 5 mg/kg

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

crizanlizumab

Other Intervention Name(s)

SEG101

Intervention Description

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

Primary Outcome Measure Information:

Title

To characterize PK (AUC) of crizanlizumab at 5.0 mg/kg in SCD patients.

Description

PK (AUC)

Time Frame

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

Title

To characterize PK (Ctrough) of crizanlizumab at 5.0 mg/kg in SCD patients.

Description

PK (Ctrough)

Time Frame

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

Title

To characterize PK (Cmax) of crizanlizumab at 5.0 mg/kg in SCD patients.

Description

PK (Cmax)

Time Frame

Week1 Day1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr; Week15 Day1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr

Title

Pharmacodynamics (PD): Percentage of P-selectin inhibition and PD-AUC inhibition of crizanlizumab at 5.0 mg/kg in SCD patients

Description

P-selectin inhibition percentage & PD AUC inhibition after the starting dose, after multiple doses and prior to each study drug dose

Time Frame

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

Secondary Outcome Measure Information:

Title

Annualized rate of VOC events leading to healthcare visit in clinic/ER/hospital over time.

Description

Assess efficacy of crizanlizumab (VOC leading to healthcare visits)

Time Frame