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

• ClinicalTrials.gov Identifier: NCT03264989
• Recruitment Status: Active, not recruiting
• First Posted: August 29, 2017
• Last Update Posted: March 23, 2023
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

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 (Clinical Trial)
• 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: December 19, 2017
• Estimated Primary Completion Date: April 28, 2023
• Estimated Study Completion Date: April 28, 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 Name: SEG101

Outcome Measures

Primary Outcome Measures :

1. To characterize PK (AUC) of crizanlizumab at 5.0 mg/kg in SCD patients. [ 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 ]
   PK (AUC)
2. To characterize PK (Ctrough) of crizanlizumab at 5.0 mg/kg in SCD patients. [ 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 ]
   PK (Ctrough)
3. To characterize PK (Cmax) of crizanlizumab at 5.0 mg/kg in SCD patients. [ Time Frame: Week1 Day1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr; Week15 Day1 Pre-dose, 0.5hr, 1hr, 2hr, 4hr, 6hr, 24hr ]
   PK (Cmax)
4. Pharmacodynamics (PD): Percentage of P-selectin inhibition and PD-AUC inhibition of crizanlizumab at 5.0 mg/kg in SCD patients [ 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 ]
   P-selectin inhibition percentage & PD AUC inhibition after the starting dose, after multiple doses and prior to each study drug dose

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 70 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Florida

Novartis Investigative Site

Orange City, Florida, United States, 32763

Novartis Investigative Site

Tampa, Florida, United States, 33606

United States, Georgia

Novartis Investigative Site

Atlanta, Georgia, United States, 30342

Novartis Investigative Site

Augusta, Georgia, United States, 30912

United States, Maryland

Novartis Investigative Site

Baltimore, Maryland, United States, 21201

United States, New York

Novartis Investigative Site

Bronx, New York, United States, 10467

United States, North Carolina

Novartis Investigative Site

Durham, North Carolina, United States, 27710

Novartis Investigative Site

Greenville, North Carolina, United States, 27858

United States, Pennsylvania

Novartis Investigative Site

Philadelphia, Pennsylvania, United States, 19104-4399

United States, South Carolina

Novartis Investigative Site

Charleston, South Carolina, United States, 29425

Novartis Investigative Site

Columbia, South Carolina, United States, 29203

Novartis Investigative Site

Rock Hill, South Carolina, United States, 29732

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Study Protocol  [PDF] June 4, 2019

Statistical Analysis Plan  [PDF] November 5, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kanter J, Brown RC, Norris C, Nair SM, Kutlar A, Manwani D, Shah N, Tanaka C, Bodla S, Sanchez-Olle G, Albers U, Liles D. Pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease. Blood Adv. 2023 Mar 28;7(6):943-952. doi: 10.1182/bloodadvances.2022008209.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03264989
• Other Study ID Numbers: CSEG101A2202
• First Posted: August 29, 2017
• Last Update Posted: March 23, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• URL: http://www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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

Additional relevant MeSH terms:

Anemia, Sickle Cell; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn