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

NCT ID: NCT03264989

Last Updated: 2024-10-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-19
• Study Completion Date: 2023-06-26

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.

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 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.

Conditions

Sickle Cell Disease (SCD)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

crizanlizumab

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

Group Type: EXPERIMENTAL

crizanlizumab

Intervention Type: 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

Interventions

crizanlizumab

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

Intervention Type: DRUG

Other Intervention Names

SEG101

Eligibility 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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Orange, Florida, United States

Novartis Investigative Site

Tampa, Florida, United States

Childrens Healthcare of Atlanta .

Atlanta, Georgia, United States

Augusta University Georgia Patient Treatment

Augusta, Georgia, United States

University of Maryland Medical Ctr

Baltimore, Maryland, United States

Childrens Hospital at Montefiore

The Bronx, New York, United States

Duke University Medical Center Patient Treatment

Durham, North Carolina, United States

East Carolina University East Carolina University

Greenville, North Carolina, United States

Childrens Hospital Of Philadelphia Patient Treatment

Philadelphia, Pennsylvania, United States

Medical Uni of South Carolina Medical Univ of SC

Charleston, South Carolina, United States

M Francisco Gonzalez MD PA .

Columbia, South Carolina, United States

Carolina Blood and Cancer Care of South Carolina

Rock Hill, South Carolina, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 39497751 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36529836 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36355805 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1912

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

Other Identifiers

CSEG101A2202

Identifier Type: -

Identifier Source: org_study_id