CClinicalTrials.gg
CompletedNCT03264989Updated Oct 9, 2024Results posted

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

A Phase 2 interventional study of crizanlizumab in Sickle Cell Disease (SCD), sponsored by Novartis Pharmaceuticals. Completed at 12 sites in United States. Open to participants aged 16 Years to 70 Years. Per ClinicalTrials.gov, last updated 2024-10-09.

Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
57
Allocation
Not applicable
Ages
16 Years to 70 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Sickle Cell Disease (SCD)

Browse trials for

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
03

Who can participate

Ages eligible
16 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
57 participants (actual)

Study arms

  • Experimental
    crizanlizumab

    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

  • Drugcrizanlizumab

    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

05

What researchers measure

Primary outcomes

  1. 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)

    Time frame: 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

  2. 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).

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

  3. 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.

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

  4. 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.

    Time frame: 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

  5. 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.

    Time frame: 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

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

    To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in Sickle cell disease (SCD) patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

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

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

    To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

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

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

    To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of hospitalizations and ER visits = number of hospitalizations and ER visits reported until end date × 365.25/(End date - treatment start date + 1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

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

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

    Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients for hospitalizations and ER visits. Annualized days of all hospitalizations and ER visits = Number of days of all hospitalizations and ER visits × 365.25/(End date - treatment start date + 1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and to treat SCD and or to prevent/reduce VOCs, cut-off date).

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

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

    Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. The baseline (BL) annualized rate of VOC is defined as the number of VOCs reported in the last 12 months in the eCRF. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

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

  6. Annualized Rate of VOC Events (Including Both Healthcare Visit and Home Treatment)

    Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date -date of first dose of study treatment+1). End date is defined as th e minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

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

  7. Number of Participants With Immunogenicity (IG) by Any Positive Status

    Assess safety and tolerability of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients by the percentage of participants with any positive status. Immunogenicity is the measurement of anti-drug antibodies (ADA) to crizanlizumab.

    Time frame: Baseline (Week 1), post-baseline (approx. 45 months (median exposure))

06

Results

Posted Apr 23, 2024
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.

Participant flow

57 patients were enrolled sequentially to study the at 5 mg/kg arm and at 7.5 mg/kg.

Participant flow — Overall Study
MilestoneCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kg
Started4512
Completed00
Not completed4512
Withdrew: Lost to follow-up10
Withdrew: New therapy for study indication10
Withdrew: Protocol violation01
Withdrew: Patient decision130
Withdrew: Physician decision64
Withdrew: Adverse event21
Withdrew: Death11
Withdrew: Pregnancy20
Withdrew: End of study195

Outcome measures

PrimaryPharmacokinetic (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)

Time frame:
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
Reported as:
Mean · hr*μg/mL
Pharmacokinetic (PK): AUCd15 and AUCtau of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients
hr*μg/mLCrizanlizumab 5.0 mg/kg
Starting dose (Week 1): AUCd1513100 ± 2810
Steady State (Week 15): AUCtau20800 ± 5030
PrimaryPK: 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).

Time frame:
After the starting dose (Week 1) and after multiple doses (steady state, Week 15)
Reported as:
Mean · μg/mL
PK: Cmax of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients
μg/mLCrizanlizumab 5.0 mg/kg
Starting dose (Week 1)102 ± 29.8
Steady State (Week 15)123 ± 36.4
PrimaryPre-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.

Time frame:
Pre-dose at Day 1 on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51
Reported as:
Mean · μg/mL
Pre-dose Concentrations Prior to Each Study Drug Dose
μg/mLCrizanlizumab 5.0 mg/kg
Week (W) 3 Day 1 (D)1: 0 hrs pre-dose18.0 ± 6.42
W7 D1: 0 hrs pre-dose10.8 ± 5.21
W11 D1: 0 hrs pre-dose9.04 ± 5.04
W15 D1: 0 hrs pre-dose10.0 ± 5.39
W19 D1: 0 hrs pre-dose9.37 ± 4.95
W23 D1: 0 hrs pre-dose9.91 ± 5.09
W27 D1: 0 hrs pre-dose9.65 ± 4.03
W31 D1: 0 hrs pre-dose9.75 ± 4.66
W35 D1: 0 hrs pre-dose9.48 ± 4.60
W39 D1: 0 hrs pre-dose9.54 ± 5.47
W43 D1: 0 hrs pre-dose8.53 ± 5.24
W47 D1: 0 hrs pre-dose8.96 ± 4.31
W51 D1: 0 hrs pre-dose8.45 ± 4.88
PrimaryPercentage 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.

Time frame:
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
Reported as:
Mean · hours*% of P-selectin inhibition
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
hours*% of P-selectin inhibitionCrizanlizumab 5.0 mg/kg
Starting dose (Week 1): PD-AUCd1533200 ± 1830
Steady state (Week 15): PD-AUCd2966900 ± 5540
SecondaryAnnualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic/Emergency Room (ER)/Hospital

To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in Sickle cell disease (SCD) patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

Time frame:
Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Reported as:
Median · number of events per year
Annualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic/Emergency Room (ER)/Hospital
number of events per yearCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kg
Baseline annualized rate of VOC4.00 (1.0 to 25.0)2.00 (1.0 to 9.0)
Annualized rate of VOC on treatment2.75 (0.0 to 17.3)0.97 (0.0 to 7.9)
SecondaryAnnualized Rate of VOC Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With Patient)

To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

Time frame:
Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Reported as:
Median · number of events per participant-year
Annualized Rate of VOC Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With Patient)
number of events per participant-yearCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kg
Annualized Rate of VOC Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With Patient)0.68 (0.21 to 2.17)0.71 (0.35 to 1.74)
SecondaryAnnualized Rate of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits

To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of hospitalizations and ER visits = number of hospitalizations and ER visits reported until end date × 365.25/(End date - treatment start date + 1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

Time frame:
Baseine (Week 1) through approx. 45 months (median exposure to treatment)
Reported as:
Median · number of events per participant-year
Annualized Rate of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits
number of events per participant-yearCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kg
Annualized rate (total)3.42 (0.0 to 57.8)2.47 (0.0 to 8.1)
Annualized rate (VOC related)3.34 (0.0 to 57.8)0.86 (0.0 to 7.9)
Hospitalizations/ER Annualized rate (total)2.46 (0.0 to 22.1)1.44 (0.0 to 7.9)
Hospitalizations/ER Annualized rate (VOC related)2.27 (0.0 to 22.1)0.48 (0.0 to 7.9)
SecondaryAnnualized Days of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits

Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients for hospitalizations and ER visits. Annualized days of all hospitalizations and ER visits = Number of days of all hospitalizations and ER visits × 365.25/(End date - treatment start date + 1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and to treat SCD and or to prevent/reduce VOCs, cut-off date).

Time frame:
Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Reported as:
Median · number of days per year
Annualized Days of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits
number of days per yearCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kg
Annualized days (total)11.95 (0.0 to 86.2)3.17 (0.0 to 36.8)
Annualized days (VOC related)9.03 (0.0 to 86.2)1.57 (0.0 to 36.8)
Hospitalizations/ER Annualized days (total)10.31 (0.0 to 69.4)2.57 (0.0 to 36.8)
Hospitalizations/ER Annualized days (VOC related)7.27 (0.0 to 69.4)0.60 (0.0 to 36.8)
SecondaryAnnualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs))

Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. The baseline (BL) annualized rate of VOC is defined as the number of VOCs reported in the last 12 months in the eCRF. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

Time frame:
Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Reported as:
Median · number of events per year
Annualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs))
number of events per yearCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kg
BL annualized rate of VOC: ACS0.00 (0.0 to 2.0)0.00 (0.0 to 2.0)
Annualized rate of VOC on treatment: ACS0.62 (0.0 to 2.7)0.25 (0.0 to 0.6)
BL annualized rate of VOC: Priapism1.00 (0.0 to 4.0)—
Annualized rate of VOC on treatment: Priapism1.58 (0.0 to 3.8)—
BL annualized rate of VOC: Uncomplicated SC-VOCs3.00 (1.0 to 25.0)2.00 (1.0 to 9.0)
Annualized rate of VOC on treatment: Uncomplicated SC-VOCs2.58 (0.0 to 17.3)1.04 (0.0 to 7.9)
SecondaryAnnualized Rate of VOC Events (Including Both Healthcare Visit and Home Treatment)

Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date -date of first dose of study treatment+1). End date is defined as th e minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

Time frame:
Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Reported as:
Median · number of events per year
Annualized Rate of VOC Events (Including Both Healthcare Visit and Home Treatment)
number of events per yearCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kg
Annualized Rate of VOC Events (Including Both Healthcare Visit and Home Treatment)3.42 (0.0 to 17.3)1.65 (0.0 to 9.3)
SecondaryNumber of Participants With Immunogenicity (IG) by Any Positive Status

Assess safety and tolerability of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients by the percentage of participants with any positive status. Immunogenicity is the measurement of anti-drug antibodies (ADA) to crizanlizumab.

Time frame:
Baseline (Week 1), post-baseline (approx. 45 months (median exposure))
Reported as:
Number · Participants
Number of Participants With Immunogenicity (IG) by Any Positive Status
ParticipantsCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kgAll Participants
Baseline: Positive000
Post-Baseline: Any Positive000
PrimaryPercentage 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.

Time frame:
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)
Reported as:
Mean · percentage of P-selectin inhibition
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients
percentage of P-selectin inhibitionCrizanlizumab 5.0 mg/kg
Week (W) 3 Day (D) 1: 0 hrs pre-dose97.3 ± 7.49
W7D1: 0 hrs pre-dose93.0 ± 17.1
W11D1: 0 hrs pre-dose87.8 ± 22.6
W15D1: 0 hrs pre-dose94.1 ± 12.8
WD19: 0 hrs pre-dose91.7 ± 18.5
W23D1: 0 hrs pre-dose93.2 ± 14.9
W27D1: 0 hrs pre-dose94.3 ± 13.0
W31D1: 0 hrs pre-dose92.4 ± 18.9
W35D1: 0 hrs pre-dose91.7 ± 14.7
W39D1: 0 hrs pre-dose88.5 ± 21.2
W43D1: 0 hrs pre-dose86.1 ± 24.8
W47D1: 0 hrs pre-dose92.1 ± 16.8
W51D1: 0 hrs pre-dose91.5 ± 17.6

Adverse events

Collected over All deaths, Serious Adverse Events, and Other Adverse Events for both 'Treatment phase' and 'Post-treatment follow-up phase' (up to 105 days after the last dose of study treatment) were reported. The median duration of exposure to crizanlizumab was 206.1 weeks in the 5.0 mg/kg dose group and 169.6 weeks in the 7.5 mg/kg dose group.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Crizanlizumab 5.0 mg/kg1/45 (2.2%)22/45 (48.9%)42/45 (93.3%)
Crizanlizumab 7.5 mg/kg1/12 (8.3%)6/12 (50%)11/12 (91.7%)
All Participants2/57 (3.5%)28/57 (49.1%)53/57 (93%)
Most frequent serious events
Showing 10 of 59
Most frequent serious events
EventCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kgAll Participants
AnaemiaBlood and lymphatic system disorders0/451/121/57
CytopeniaBlood and lymphatic system disorders0/451/121/57
Cardiac arrestCardiac disorders0/451/121/57
PyrexiaGeneral disorders1/451/122/57
CholelithiasisHepatobiliary disorders0/451/121/57
HypertransaminasaemiaHepatobiliary disorders0/451/121/57
Ischaemic hepatitisHepatobiliary disorders0/451/121/57
Anaphylactic reactionImmune system disorders0/451/121/57
AppendicitisInfections and infestations0/451/121/57
COVID-19Infections and infestations3/451/124/57
Most frequent other events
Showing 10 of 76
Most frequent other events
EventCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kgAll Participants
PyrexiaGeneral disorders13/453/1216/57
HypokalaemiaMetabolism and nutrition disorders12/452/1214/57
HeadacheNervous system disorders12/452/1214/57
VomitingGastrointestinal disorders4/453/127/57
Upper respiratory tract infectionInfections and infestations10/452/1212/57
ArthralgiaMusculoskeletal and connective tissue disorders8/452/1210/57
ConstipationGastrointestinal disorders3/452/125/57
DiarrhoeaGastrointestinal disorders4/452/126/57
NauseaGastrointestinal disorders6/452/128/57
Ocular icterusHepatobiliary disorders1/452/123/57

Baseline characteristics

Full Analysis Set (FAS): Consisted of all patients to whom crizanlizumab had been assigned and who received at least 1 dose of study treatment.

Age, Continuous
Age, Continuous(years)Crizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kgTotal
Mean32.3 ± 12.7126.8 ± 12.2531.2 ± 12.71
Age, Customized
Age, Customized(participants)Crizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kgTotal
16 - < 18 years123
18 - < 65 years431053
65 - < 70 years101
Sex: Female, Male
Sex: Female, Male(Participants)Crizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kgTotal
Female25631
Male20626
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Crizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kgTotal
Black or African American441256
White and Black or African American101
07

Study locations

12 sites
  • Novartis Investigative Site
    Orange, Florida 32763, United States
  • Novartis Investigative Site
    Tampa, Florida 33606, United States
  • Childrens Healthcare of Atlanta .
    Atlanta, Georgia 30342, United States
  • Augusta University Georgia Patient Treatment
    Augusta, Georgia 30912, United States
  • University of Maryland Medical Ctr
    Baltimore, Maryland 21201, United States
  • Childrens Hospital at Montefiore
    Bronx, New York 10467, United States
  • Duke University Medical Center Patient Treatment
    Durham, North Carolina 27710, United States
  • East Carolina University East Carolina University
    Greenville, North Carolina 27858, United States
  • Childrens Hospital Of Philadelphia Patient Treatment
    Philadelphia, Pennsylvania 19104-4399, United States
  • Medical Uni of South Carolina Medical Univ of SC
    Charleston, South Carolina 29425, United States
  • M Francisco Gonzalez MD PA .
    Columbia, South Carolina 29203, United States
  • Carolina Blood and Cancer Care of South Carolina
    Rock Hill, South Carolina 29732, United States
08

References and documents

Publications

  • 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. PubMed 36355805 ↗

Study documents

  • Study protocol · Jun 4, 2018
  • Statistical analysis plan · Nov 5, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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

09

Registry details

Key details

Study ID
NCT03264989
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Aug 29, 2017
Start date
Dec 19, 2017
Primary completion
Jun 26, 2023
Completion
Jun 26, 2023
Results posted
Apr 23, 2024
Last update
Oct 9, 2024

Study contacts

Novartis Pharmaceuticals
study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2024. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion