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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 : Recruiting
First Posted : August 29, 2017
Last Update Posted : October 9, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

The purpose of the CSEG101A2202 study is 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 is designed as a Phase II, multicenter, open-label study. The first 45 patients (to identify 27 evaluable patients) will be 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 will also be collected prior to each dose. In addition, throughout the study (and when possible), all patients will have 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 are enrolled, 10 additional patients will be enrolled to the exploratory treatment group and begin at 7.5 mg/kg of crizanlizumab.


Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: crizanlizumab Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
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 : November 9, 2020
Estimated Study Completion Date : November 9, 2020


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: 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 ]
    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. To characterize PD (AUC for P-selectin 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 ]
    PD (AUC for P-selectin inhibition)


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)



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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

Other protocol-defined Inclusion/Exclusion criteria may apply.


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


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.Email@novartis.com
Contact: Novartis Pharmaceuticals

Locations
United States, Florida
University of Miami Patient Treatment Recruiting
Miami, Florida, United States, 33136
Contact: Vanessa Cumming    305-243-9431    v.cumming@med.miami.edu   
Principal Investigator: Ofelia Alvarez         
Florida Cancer Affiliates of Ocala Recruiting
Ocala, Florida, United States, 34471
Contact: Stacy McCombs    352-732-4032    stacy.mccombs@usoncology.com   
Principal Investigator: Rama Balaraman         
Mid Florida Hematology and Oncology Center Recruiting
Orange City, Florida, United States, 32763
Contact: Kiran Kumar Penta    386-774-1223    kiran@clorene.org   
Principal Investigator: Santosh Nair         
Tampa General Hospital Recruiting
Tampa, Florida, United States, 33606
Contact: Stephenie Yapchanyk    (813) 541-0254    syapchanyk@tgh.org   
Principal Investigator: Juan Felipe Rico         
United States, Georgia
Childrens Healthcare of Atlanta Recruiting
Atlanta, Georgia, United States, 30342
Contact: Katherine Garrett    407-785-2025    Katherine.garrett@choa.org   
Principal Investigator: Robert Clark Brown         
Augusta University Georgia Cancer Center Pharmacy Patient Treatment Recruiting
Augusta, Georgia, United States, 30912
Contact: Leigh G. Wells    706-721-2171    lwells@augusta.edu   
Principal Investigator: Abdullah Kutlar         
United States, Maryland
University of Maryland Medical Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Carolynn Harris    420-438-8199    charris@umm.edu   
Principal Investigator: Jennie Law         
United States, New Jersey
Regional Cancer Care Associates RCCA MD LLC Recruiting
Cherry Hill, New Jersey, United States, 08003
Contact: Jennifer Cipriano    301-571-2016    jcipriano@ccbdmd.com   
Principal Investigator: Ralph V Boccia         
Rutgers Robert Wood Johnson Medical School Recruiting
New Brunswick, New Jersey, United States, 08901
Contact: Kim White    732-235-7678    kim.a.white@rutgers.edu   
Principal Investigator: Amanda Kaveney         
United States, New York
Children's Hospital at Montefiore Recruiting
Bronx, New York, United States, 10467
Contact: Jill Fillipelli    718-741-2384    jfilipelli@brany.com   
Principal Investigator: Deepa Manwani         
United States, North Carolina
Duke University Medical Center Patient Treatment Recruiting
Durham, North Carolina, United States, 27710
Contact: Elizabeth Thames    919-668-5178    elizabeth.thames@dm.duke.edu   
Principal Investigator: Nirmish Shah         
East Carolina University East Carolina University Recruiting
Greenville, North Carolina, United States, 27858
Contact: Sue Ann Joyner    +1 252 744 0456    joynersu@ecu.edu   
Principal Investigator: Darla K. Liles         
United States, Pennsylvania
Children's Hospital of Philadelphia Patient Treatment Recruiting
Philadelphia, Pennsylvania, United States, 19104-4399
Contact: Courtney Babb    267-426-9338    babbc@email.chop.edu   
Principal Investigator: Kim Smith Whitley         
United States, South Carolina
Medical University of South Carolina Medical Univ of SC Recruiting
Charleston, South Carolina, United States, 29425
Contact: Joannie Hayes    843-876-8614    hayesj@musc.edu   
Principal Investigator: Julie Kanter-Washko         
M Francisco Gonzalez MD PA Recruiting
Columbia, South Carolina, United States, 29203
Contact: Sharon Goff    803-840-8890    skgoff2002@yahoo.com   
Principal Investigator: M. Francisco Gonzalez         
Carolina Blood and Cancer Care of South Carolina Recruiting
Rock Hill, South Carolina, United States, 29732
Contact: Dhwani Mehta    803-329-7772    dmehta@cbcca.net   
Principal Investigator: Niyati Nathwani         
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03264989     History of Changes
Other Study ID Numbers: CSEG101A2202
First Posted: August 29, 2017    Key Record Dates
Last Update Posted: October 9, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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
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