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

NCT03264989 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CSEG101A2202
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 12

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (5)

• Pharmacokinetic (PK): AUCd15 and AUCtau of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients

  To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients. AUCd15: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) after single dose AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1)

  1st dose: Day 1: (pre-dose, 0.5, 1, 2, 4, 6 & 24 hours post dose, Days 4, 8 & 15; 5th dose: Day 1 (pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose), Days 4, 8, 15, 22 & 29

• PK: Cmax of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients

  To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients. Cmax: The maximum (peak) observed serum drug concentration after dose administration (mass x volume-1).

  After the starting dose (Week 1) and after multiple doses (steady state, Week 15)

• Pre-dose Concentrations Prior to Each Study Drug Dose

  To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients, by serum concentrations by treatment group. Data was collected prior to each study drug dose; From Week 3 (loading dose), pre-dose (trough) concentrations were obtained every 4 weeks.

  Pre-dose at Day 1 on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51

• 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

  PD-AUCd15 and PD-AUCd29 were derived from the P-selectin inhibition data of week 1 and week 15, respectively. To characterize PD of crizanlizumab at 5.0 mg/kg in SCD patients The area under the curve (AUC) of percentage of P-selectin inhibition versus time profile after the starting dose (PD-AUCd15) and after multiple doses (PD-AUCd29) is being reported.

  1st dose: Day 1: (pre-dose, 0.5, 1, 2, 4, 6 & 24 hours post dose, Days 4, 8, 15; 5th dose: Day 1(pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose), Days 4, 8, 15, 22 & 29

• Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients

  To characterize the PD effect of crizanlizumab in terms of Percentage of P-selectin inhibition prior to study drug dose at 5 mg/kg in CSD patients.

  Pre-dose on Day 1 for Weeks 3, 7, 11, 15, 19, 23, 27, 31,35, 39, 43, 47, 51 (at 0 hr or pre-dose)

Secondary Outcomes (7)

• Annualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic/Emergency Room (ER)/Hospital

  Baseline (Week 1) through approx. 45 months (median exposure to treatment)

• Annualized Rate of VOC Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With Patient)

  Baseline (Week 1) through approx. 45 months (median exposure to treatment)

• Annualized Rate of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits

  Baseine (Week 1) through approx. 45 months (median exposure to treatment)

• Annualized Days of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits

  Baseline (Week 1) through approx. 45 months (median exposure to treatment)

• Annualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs))

  Baseline (Week 1) through approx. 45 months (median exposure to treatment)

Study Arms (1)

crizanlizumab

EXPERIMENTAL

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

Drug: crizanlizumab

Interventions

crizanlizumab DRUG

Crizanlizumab was administered IV infusion over 30 minutes at the assigned dose on Week 1 Day 1, Week 3 Day 1, and then Day 1 of every 4-week cycle. Cycle = 28 days

Also known as: SEG101

crizanlizumab

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Novartis Investigative Site

Orange, Florida, 32763, United States

Location

Novartis Investigative Site

Tampa, Florida, 33606, United States

Location

Childrens Healthcare of Atlanta .

Atlanta, Georgia, 30342, United States

Location

Augusta University Georgia Patient Treatment

Augusta, Georgia, 30912, United States

Location

University of Maryland Medical Ctr

Baltimore, Maryland, 21201, United States

Location

Childrens Hospital at Montefiore

The Bronx, New York, 10467, United States

Location

Duke University Medical Center Patient Treatment

Durham, North Carolina, 27710, United States

Location

East Carolina University East Carolina University

Greenville, North Carolina, 27858, United States

Location

Childrens Hospital Of Philadelphia Patient Treatment

Philadelphia, Pennsylvania, 19104-4399, United States

Location

Medical Uni of South Carolina Medical Univ of SC

Charleston, South Carolina, 29425, United States

Location

M Francisco Gonzalez MD PA .

Columbia, South Carolina, 29203, United States

Location

Carolina Blood and Cancer Care of South Carolina

Rock Hill, South Carolina, 29732, United States

Location

Related Publications (3)

• Kanter J, Mennito S, Nair SM, Manwani D, Kutlar A, Shah N, Keefe D, Madhamshetty H, Nassin M, Reshetnyak E, Mendonza AE, Liles D. Pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease: final results from the phase II SOLACE-adults study. Ther Adv Hematol. 2024 Nov 3;15:20406207241292508. doi: 10.1177/20406207241292508. eCollection 2024.

  PMID: 39497751 DERIVED

• Sy SKB, Tanaka C, Grosch K. Population Pharmacokinetics and Pharmacodynamics of Crizanlizumab in Healthy Subjects and Patients with Sickle Cell Disease. Clin Pharmacokinet. 2023 Feb;62(2):249-266. doi: 10.1007/s40262-022-01193-4. Epub 2022 Dec 18.

  PMID: 36529836 DERIVED

• 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.

  PMID: 36355805 DERIVED

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Anemia, Sickle Cell; Vaso-Occlusive Crises; Hemoglobin SC Disease

Interventions

crizanlizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

This study provided a 5-year follow up (f/u) data that fully characterized the safety, tolerability \& treatment of the 5.0 mg/kg \& 7.5 mg/kg doses of crizanlizumab along with the initially planned PK \& PD data. As the goal of study f/u was reached, study was considered completed \& it was in line with the end of study as defined in the study protocol, the sponsor closed the study as the participants were no longer receiving intervention or being examined.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2017
• First Posted: August 29, 2017
• Study Start: December 19, 2017
• Primary Completion: June 26, 2023
• Study Completion: June 26, 2023
• Last Updated: October 9, 2024
• Results First Posted: April 23, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

US (12)