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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 : March 26, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE August 4, 2017
First Posted Date  ICMJE August 29, 2017
Last Update Posted Date March 26, 2019
Actual Study Start Date  ICMJE December 19, 2017
Estimated Primary Completion Date February 19, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2018)
  • 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)
  • 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)
  • 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)
  • 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)
Original Primary Outcome Measures  ICMJE
 (submitted: August 25, 2017)
  • To characterize PK (AUC) of crizanlizumab at 5.0 mg/kg in adult 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)
  • To characterize PK (Ctrough) of crizanlizumab at 5.0 mg/kg in adult 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)
  • To characterize PK (Cmax) of crizanlizumab at 5.0 mg/kg in adult 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)
  • To characterize PD (AUC for P-selectin inhibition) of crizanlizumab at 5.0 mg/kg in adult 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)
Change History Complete list of historical versions of study NCT03264989 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2018)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2017)
  • Number 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)
  • Number 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)
  • Number 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)
  • Number of each subcategory of VOC event (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)
  • Number 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)
  • 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)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics and Pharmacodynamics Study of SEG101 (Crizanlizumab) in Sickle Cell Disease (SCD) Patients With Vaso- Occlusive Crisis (VOC)
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE 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
Study Arms  ICMJE 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.
Intervention: Drug: crizanlizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 25, 2017)
55
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 19, 2021
Estimated Primary Completion Date February 19, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.Email@novartis.com
Contact: Novartis Pharmaceuticals
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03264989
Other Study ID Numbers  ICMJE CSEG101A2202
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP