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

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ClinicalTrials.gov Identifier: NCT03264989
Recruitment Status : Active, not recruiting
First Posted : August 29, 2017
Last Update Posted : July 28, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

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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 : June 30, 2021
Estimated Study Completion Date : June 30, 2021


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




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)



Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03264989


Locations
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United States, Florida
Mid Florida Hematology and Oncology Center
Orange City, Florida, United States, 32763
Tampa General Hospital
Tampa, Florida, United States, 33606
United States, Georgia
Childrens Healthcare of Atlanta
Atlanta, Georgia, United States, 30342
Augusta University Georgia Cancer Center Pharmacy Patient Treatment
Augusta, Georgia, United States, 30912
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, New York
Children's Hospital at Montefiore
Bronx, New York, United States, 10467
United States, North Carolina
Duke University Medical Center Patient Treatment
Durham, North Carolina, United States, 27710
East Carolina University East Carolina University
Greenville, North Carolina, United States, 27858
United States, Pennsylvania
Children s Hospital of Philadelphia Patient Treatment
Philadelphia, Pennsylvania, United States, 19104-4399
United States, South Carolina
Medical University of South Carolina Medical Univ of SC
Charleston, South Carolina, United States, 29425
M Francisco Gonzalez MD PA
Columbia, South Carolina, United States, 29203
Carolina Blood and Cancer Care of South Carolina
Rock Hill, South Carolina, United States, 29732
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Statistical Analysis Plan  [PDF] November 5, 2018
Study Protocol  [PDF] June 4, 2019

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03264989    
Other Study ID Numbers: CSEG101A2202
First Posted: August 29, 2017    Key Record Dates
Last Update Posted: July 28, 2020
Last Verified: July 2020
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

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