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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| crizanlizumab | Experimental | SEG101 (crizanlizumab) drug at a dose of 5.0 mg/kg (or 7.5 mg/kg for exploratory group) by IV infusion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| crizanlizumab | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 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 |
| 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). | After the starting dose (Week 1) and after multiple doses (steady state, Week 15) |
| 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. | Pre-dose at Day 1 on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51 |
| 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. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Orange | Florida | 32763 | United States | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39497751 | Derived | 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. | |
| 36529836 |
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on www.novctrd.com | View source |
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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
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This study was conducted in 12 centers in the United States only.
57 patients were enrolled sequentially to study the at 5 mg/kg arm and at 7.5 mg/kg.
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| ID | Title | Description |
|---|---|---|
| FG000 | Crizanlizumab 5.0 mg/kg | Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion. |
| FG001 | Crizanlizumab 7.5 mg/kg | Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 4, 2018 | Dec 14, 2019 |
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|
| 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. | 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) |
| Baseline (Week 1) through approx. 45 months (median exposure to treatment) |
| 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). | Baseline (Week 1) through approx. 45 months (median exposure to treatment) |
| 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). | Baseine (Week 1) through approx. 45 months (median exposure to treatment) |
| 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). | Baseline (Week 1) through approx. 45 months (median exposure to treatment) |
| 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). | Baseline (Week 1) through approx. 45 months (median exposure to treatment) |
| 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). | Baseline (Week 1) through approx. 45 months (median exposure to treatment) |
| 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. | Baseline (Week 1), post-baseline (approx. 45 months (median exposure)) |
| 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 | The 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 |
| Derived |
| 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. |
| 36355805 | Derived | 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. |
| COMPLETED | Completed = Treatment ongoing. Not Completed = Discontinued from treatment |
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| NOT COMPLETED |
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Full Analysis Set (FAS): Consisted of all patients to whom crizanlizumab had been assigned and who received at least 1 dose of study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Crizanlizumab 5.0 mg/kg | Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion. |
| BG001 | Crizanlizumab 7.5 mg/kg | Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Number | participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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) | The PK analysis set 1 (PAS1) included all patients who provided at least one evaluable PK profile in the 5.0 mg/kg arm. | Posted | Mean | Standard Deviation | hr*μg/mL | 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 |
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| Primary | 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). | The PK analysis set 1 (PAS1) included all patients who provided at least one evaluable PK profile in the 5.0 mg/kg arm. The Cmax analysis was done on all participants including those for at starting dose (n =42) and steady state (n = 36). | Posted | Mean | Standard Deviation | μg/mL | After the starting dose (Week 1) and after multiple doses (steady state, Week 15) |
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| Primary | 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. | PK Analysis set 2 (PAS2): Included all patients who received at least one planned treatment of 5 mg/kg and provided at least one corresponding evaluable PK concentration. | Posted | Mean | Standard Deviation | μg/mL | Pre-dose at Day 1 on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51 |
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| Primary | 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. | PDS1 included all patients who provided at least 1 evaluable PD profile. The P-selectin inhibition analysis was done on all participants including those starting dose (n = 36) and steady state (n = 33). | Posted | Mean | Standard Deviation | hours*% of P-selectin inhibition | 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 |
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| Secondary | 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). | The Full analysis set (FAS) consisted of all patients to whom crizanlizumab had been assigned and who received at least one dose of study treatment. | Posted | Median | Full Range | number of events per year | Baseline (Week 1) through approx. 45 months (median exposure to treatment) |
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| Secondary | 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). | The Full analysis set (FAS) consisted of all patients to whom crizanlizumab had been assigned and who received at least one dose of study treatment. The annualized rate of VOC events treated at home analyzed all participants including those who had a VOC event treated at home in the Crizanlizumab 5.0 mg/kg arm and in the Crizanlizumab 7.5 mg/kg arm. | Posted | Median | Full Range | number of events per participant-year | Baseline (Week 1) through approx. 45 months (median exposure to treatment) |
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| Secondary | 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). | The Full analysis set (FAS) consisted of all patients to whom crizanlizumab had been assigned and who received at least one dose of study treatment. | Posted | Median | Full Range | number of events per participant-year | Baseine (Week 1) through approx. 45 months (median exposure to treatment) |
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| Secondary | 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). | The Full analysis set (FAS) consisted of all patients to whom crizanlizumab had been assigned and who received at least one dose of study treatment. | Posted | Median | Full Range | number of days per year | Baseline (Week 1) through approx. 45 months (median exposure to treatment) |
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| Secondary | 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). | The Full analysis set (FAS) consisted of all patients to whom crizanlizumab had been assigned and who received at least one dose of study treatment. | Posted | Median | Full Range | number of events per year | Baseline (Week 1) through approx. 45 months (median exposure to treatment) |
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| Secondary | 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). | The Full analysis set (FAS) consisted of all patients to whom crizanlizumab had been assigned and who received at least one dose of study treatment. | Posted | Median | Full Range | number of events per year | Baseline (Week 1) through approx. 45 months (median exposure to treatment) |
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| Secondary | 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. | The Full analysis set (FAS) consisted of all patients to whom crizanlizumab had been assigned and who received at least one dose of study treatment. | Posted | Number | Participants | Baseline (Week 1), post-baseline (approx. 45 months (median exposure)) |
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| Primary | 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. | Patients in the PD analysis set 2 (PDS2) with an available value for the outcome measure. PDS2 included all patients who received at least one planned treatment of 5.0 mg/kg and provided at least one corresponding evaluable PD assessment. | Posted | Mean | Standard Deviation | percentage of P-selectin inhibition | 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) |
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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.
Any sign or symptom that occurs during the conduct of the trial and safety follow-up.
Other Adverse Event: An adverse event that is not a serious adverse event, meaning that it does not result in death, is not life-threatening, does not require inpatient hospitalization or extend a current hospital stay, does not result in an ongoing or significant incapacity or interfere substantially with normal life functions, and does not cause a congenital anomaly or birth defect.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Crizanlizumab 5.0 mg/kg | Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion. | 1 | 45 | 22 | 45 | 42 | 45 |
| EG001 | Crizanlizumab 7.5 mg/kg | Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion. | 1 | 12 | 6 | 12 | 11 | 12 |
| EG002 | All Participants | Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion. | 2 | 57 | 28 | 57 | 53 | 57 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
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| Cytopenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
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| Sickle cell anaemia with crisis | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
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| Acute myocardial infarction | Cardiac disorders | MedDRA (26.0) | Systematic Assessment |
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| Cardiac arrest | Cardiac disorders | MedDRA (26.0) | Systematic Assessment |
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| Vertigo positional | Ear and labyrinth disorders | MedDRA (26.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
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| Diverticulum | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
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| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
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| Mouth ulceration | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
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| Tooth erosion | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
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| Chest pain | General disorders | MedDRA (26.0) | Systematic Assessment |
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| Gait disturbance | General disorders | MedDRA (26.0) | Systematic Assessment |
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| Multiple organ dysfunction syndrome | General disorders | MedDRA (26.0) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Ischaemic hepatitis | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Arthritis infective | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Device related bacteraemia | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Endocarditis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Rhinovirus infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Salmonella bacteraemia | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Staphylococcal bacteraemia | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Wound sepsis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Gun shot wound | Injury, poisoning and procedural complications | MedDRA (26.0) | Systematic Assessment |
| |
| Post-traumatic pain | Injury, poisoning and procedural complications | MedDRA (26.0) | Systematic Assessment |
| |
| Tendon rupture | Injury, poisoning and procedural complications | MedDRA (26.0) | Systematic Assessment |
| |
| SARS-CoV-2 test positive | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Hyperglycaemic hyperosmolar nonketotic syndrome | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (26.0) | Systematic Assessment |
| |
| Brain injury | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Nervous system disorder | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Subarachnoid haemorrhage | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Prostatomegaly | Reproductive system and breast disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Supraventricular extrasystoles | Cardiac disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Tornwaldt cyst | Congenital, familial and genetic disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Deafness neurosensory | Ear and labyrinth disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Tympanic membrane perforation | Ear and labyrinth disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Retinal detachment | Eye disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Retinal drusen | Eye disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Retinopathy sickle cell | Eye disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Drug withdrawal syndrome | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Ocular icterus | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Acute sinusitis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Otitis media acute | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Post-traumatic pain | Injury, poisoning and procedural complications | MedDRA (26.0) | Systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA (26.0) | Systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA (26.0) | Systematic Assessment |
| |
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA (26.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Haematocrit decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hyperamylasaemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Osteosclerosis | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Tendon disorder | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Microalbuminuria | Renal and urinary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Micturition urgency | Renal and urinary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Urine odour abnormal | Renal and urinary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Dermal cyst | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (26.0) | Systematic Assessment |
|
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.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | novartis.email@novartis.com |
| Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 5, 2018 | Dec 14, 2019 | SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| D000098644 | Vaso-Occlusive Crises |
| D006450 | Hemoglobin SC Disease |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Not provided
Not provided
| ID | Term |
|---|---|
| C000614139 | crizanlizumab |
Not provided
Not provided
Not provided
| 18 - < 65 years |
|
| 65 - < 70 years |
|
| Male |
|
| White and Black or African American |
|
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| Participants |
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| Participants |
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