Trial Outcomes & Findings for Pharmacokinetics and Pharmacodynamics Study of SEG101 (Crizanlizumab) in Sickle Cell Disease (SCD) Patients With Vaso- Occlusive Crisis (VOC) (NCT NCT03264989)

Last Updated: 2024-10-09

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

57 participants

Primary outcome timeframe

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

Results posted on

2024-10-09

Participant Flow

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

This study was conducted in 12 centers in the United States only.

Participant milestones

Participant milestones
Measure	Crizanlizumab 5.0 mg/kg Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.
Overall Study STARTED	45	12
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	45	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Crizanlizumab 5.0 mg/kg Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.
Overall Study Lost to Follow-up	1	0
Overall Study New Therapy for study Indication	1	0
Overall Study Protocol Violation	0	1
Overall Study Patient decision	13	0
Overall Study Physician Decision	6	4
Overall Study Adverse Event	2	1
Overall Study Death	1	1
Overall Study Pregnancy	2	0
Overall Study End of Study	19	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Crizanlizumab 5.0 mg/kg n=45 Participants Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg n=12 Participants Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	Total n=57 Participants Total of all reporting groups
Age, Continuous	32.3 years STANDARD_DEVIATION 12.71 • n=5 Participants	26.8 years STANDARD_DEVIATION 12.25 • n=7 Participants	31.2 years STANDARD_DEVIATION 12.71 • n=5 Participants
Age, Customized 16 - < 18 years	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Age, Customized 18 - < 65 years	43 participants n=5 Participants	10 participants n=7 Participants	53 participants n=5 Participants
Age, Customized 65 - < 70 years	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	6 Participants n=7 Participants	31 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	6 Participants n=7 Participants	26 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	44 participants n=5 Participants	12 participants n=7 Participants	56 participants n=5 Participants
Race/Ethnicity, Customized White and Black or African American	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Population: The PK analysis set 1 (PAS1) included all patients who provided at least one evaluable PK profile in the 5.0 mg/kg arm.

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg n=45 Participants Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	All Participants Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion.
Pharmacokinetic (PK): AUCd15 and AUCtau of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients Starting dose (Week 1): AUCd15	13100 hr*μg/mL Standard Deviation 2810	—	—
Pharmacokinetic (PK): AUCd15 and AUCtau of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients Steady State (Week 15): AUCtau	20800 hr*μg/mL Standard Deviation 5030	—	—

PRIMARY outcome

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

Population: 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).

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).

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg n=45 Participants Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	All Participants Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion.
PK: Cmax of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients Starting dose (Week 1)	102 μg/mL Standard Deviation 29.8	—	—
PK: Cmax of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients Steady State (Week 15)	123 μg/mL Standard Deviation 36.4	—	—

PRIMARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg n=45 Participants Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	All Participants Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion.
Pre-dose Concentrations Prior to Each Study Drug Dose Week (W) 3 Day 1 (D)1: 0 hrs pre-dose	18.0 μg/mL Standard Deviation 6.42	—	—
Pre-dose Concentrations Prior to Each Study Drug Dose W7 D1: 0 hrs pre-dose	10.8 μg/mL Standard Deviation 5.21	—	—
Pre-dose Concentrations Prior to Each Study Drug Dose W11 D1: 0 hrs pre-dose	9.04 μg/mL Standard Deviation 5.04	—	—
Pre-dose Concentrations Prior to Each Study Drug Dose W15 D1: 0 hrs pre-dose	10.0 μg/mL Standard Deviation 5.39	—	—
Pre-dose Concentrations Prior to Each Study Drug Dose W19 D1: 0 hrs pre-dose	9.37 μg/mL Standard Deviation 4.95	—	—
Pre-dose Concentrations Prior to Each Study Drug Dose W23 D1: 0 hrs pre-dose	9.91 μg/mL Standard Deviation 5.09	—	—
Pre-dose Concentrations Prior to Each Study Drug Dose W27 D1: 0 hrs pre-dose	9.65 μg/mL Standard Deviation 4.03	—	—
Pre-dose Concentrations Prior to Each Study Drug Dose W31 D1: 0 hrs pre-dose	9.75 μg/mL Standard Deviation 4.66	—	—
Pre-dose Concentrations Prior to Each Study Drug Dose W35 D1: 0 hrs pre-dose	9.48 μg/mL Standard Deviation 4.60	—	—
Pre-dose Concentrations Prior to Each Study Drug Dose W39 D1: 0 hrs pre-dose	9.54 μg/mL Standard Deviation 5.47	—	—
Pre-dose Concentrations Prior to Each Study Drug Dose W43 D1: 0 hrs pre-dose	8.53 μg/mL Standard Deviation 5.24	—	—
Pre-dose Concentrations Prior to Each Study Drug Dose W47 D1: 0 hrs pre-dose	8.96 μg/mL Standard Deviation 4.31	—	—
Pre-dose Concentrations Prior to Each Study Drug Dose W51 D1: 0 hrs pre-dose	8.45 μg/mL Standard Deviation 4.88	—	—

PRIMARY outcome

Timeframe: 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

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg n=43 Participants Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	All Participants Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion.
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 Starting dose (Week 1): PD-AUCd15	33200 hours*% of P-selectin inhibition Standard Deviation 1830	—	—
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 Steady state (Week 15): PD-AUCd29	66900 hours*% of P-selectin inhibition Standard Deviation 5540	—	—

PRIMARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg n=44 Participants Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	All Participants Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion.
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients Week (W) 3 Day (D) 1: 0 hrs pre-dose	97.3 percentage of P-selectin inhibition Standard Deviation 7.49	—	—
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients W7D1: 0 hrs pre-dose	93.0 percentage of P-selectin inhibition Standard Deviation 17.1	—	—
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients W11D1: 0 hrs pre-dose	87.8 percentage of P-selectin inhibition Standard Deviation 22.6	—	—
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients W15D1: 0 hrs pre-dose	94.1 percentage of P-selectin inhibition Standard Deviation 12.8	—	—
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients WD19: 0 hrs pre-dose	91.7 percentage of P-selectin inhibition Standard Deviation 18.5	—	—
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients W23D1: 0 hrs pre-dose	93.2 percentage of P-selectin inhibition Standard Deviation 14.9	—	—
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients W27D1: 0 hrs pre-dose	94.3 percentage of P-selectin inhibition Standard Deviation 13.0	—	—
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients W31D1: 0 hrs pre-dose	92.4 percentage of P-selectin inhibition Standard Deviation 18.9	—	—
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients W35D1: 0 hrs pre-dose	91.7 percentage of P-selectin inhibition Standard Deviation 14.7	—	—
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients W39D1: 0 hrs pre-dose	88.5 percentage of P-selectin inhibition Standard Deviation 21.2	—	—
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients W43D1: 0 hrs pre-dose	86.1 percentage of P-selectin inhibition Standard Deviation 24.8	—	—
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients W47D1: 0 hrs pre-dose	92.1 percentage of P-selectin inhibition Standard Deviation 16.8	—	—
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients W51D1: 0 hrs pre-dose	91.5 percentage of P-selectin inhibition Standard Deviation 17.6	—	—

SECONDARY outcome

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

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg n=45 Participants Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg n=12 Participants Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	All Participants Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion.
Annualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic/Emergency Room (ER)/Hospital Baseline annualized rate of VOC	4.00 number of events per year Interval 1.0 to 25.0	2.00 number of events per year Interval 1.0 to 9.0	—
Annualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic/Emergency Room (ER)/Hospital Annualized rate of VOC on treatment	2.75 number of events per year Interval 0.0 to 17.3	0.97 number of events per year Interval 0.0 to 7.9	—

SECONDARY outcome

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

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg n=45 Participants Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg n=12 Participants Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	All Participants Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion.
Annualized Rate of VOC Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With Patient)	0.68 number of events per participant-year Interval 0.21 to 2.17	0.71 number of events per participant-year Interval 0.35 to 1.74	—

SECONDARY outcome

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

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg n=45 Participants Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg n=12 Participants Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	All Participants Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion.
Annualized Rate of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits Annualized rate (VOC related)	3.34 number of events per participant-year Interval 0.0 to 57.8	0.86 number of events per participant-year Interval 0.0 to 7.9	—
Annualized Rate of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits Hospitalizations/ER Annualized rate (total)	2.46 number of events per participant-year Interval 0.0 to 22.1	1.44 number of events per participant-year Interval 0.0 to 7.9	—
Annualized Rate of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits Hospitalizations/ER Annualized rate (VOC related)	2.27 number of events per participant-year Interval 0.0 to 22.1	0.48 number of events per participant-year Interval 0.0 to 7.9	—
Annualized Rate of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits Annualized rate (total)	3.42 number of events per participant-year Interval 0.0 to 57.8	2.47 number of events per participant-year Interval 0.0 to 8.1	—

SECONDARY outcome

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

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg n=45 Participants Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg n=12 Participants Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	All Participants Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion.
Annualized Days of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits Annualized days (total)	11.95 number of days per year Interval 0.0 to 86.2	3.17 number of days per year Interval 0.0 to 36.8	—
Annualized Days of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits Annualized days (VOC related)	9.03 number of days per year Interval 0.0 to 86.2	1.57 number of days per year Interval 0.0 to 36.8	—
Annualized Days of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits Hospitalizations/ER Annualized days (total)	10.31 number of days per year Interval 0.0 to 69.4	2.57 number of days per year Interval 0.0 to 36.8	—
Annualized Days of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits Hospitalizations/ER Annualized days (VOC related)	7.27 number of days per year Interval 0.0 to 69.4	0.60 number of days per year Interval 0.0 to 36.8	—

SECONDARY outcome

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

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg n=45 Participants Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg n=12 Participants Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	All Participants Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion.
Annualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs)) BL annualized rate of VOC: ACS	0.00 number of events per year Interval 0.0 to 2.0	0.00 number of events per year Interval 0.0 to 2.0	—
Annualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs)) Annualized rate of VOC on treatment: ACS	0.62 number of events per year Interval 0.0 to 2.7	0.25 number of events per year Interval 0.0 to 0.6	—
Annualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs)) BL annualized rate of VOC: Priapism	1.00 number of events per year Interval 0.0 to 4.0	—	—
Annualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs)) Annualized rate of VOC on treatment: Priapism	1.58 number of events per year Interval 0.0 to 3.8	—	—
Annualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs)) BL annualized rate of VOC: Uncomplicated SC-VOCs	3.00 number of events per year Interval 1.0 to 25.0	2.00 number of events per year Interval 1.0 to 9.0	—
Annualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs)) Annualized rate of VOC on treatment: Uncomplicated SC-VOCs	2.58 number of events per year Interval 0.0 to 17.3	1.04 number of events per year Interval 0.0 to 7.9	—

SECONDARY outcome

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

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg n=45 Participants Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg n=12 Participants Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	All Participants Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion.
Annualized Rate of VOC Events (Including Both Healthcare Visit and Home Treatment)	3.42 number of events per year Interval 0.0 to 17.3	1.65 number of events per year Interval 0.0 to 9.3	—

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg n=45 Participants Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg n=12 Participants Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	All Participants n=57 Participants Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion.
Number of Participants With Immunogenicity (IG) by Any Positive Status Baseline: Positive	0 Participants	0 Participants	0 Participants
Number of Participants With Immunogenicity (IG) by Any Positive Status Post-Baseline: Any Positive	0 Participants	0 Participants	0 Participants

Adverse Events

Crizanlizumab 5.0 mg/kg

Serious events: 22 serious events

Other events: 42 other events

Deaths: 1 deaths

Crizanlizumab 7.5 mg/kg

Serious events: 6 serious events

Other events: 11 other events

Deaths: 1 deaths

All Participants

Serious events: 28 serious events

Other events: 53 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Crizanlizumab 5.0 mg/kg n=45 participants at risk Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg n=12 participants at risk Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	All Participants n=57 participants at risk Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion.
Blood and lymphatic system disorders Anaemia	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Blood and lymphatic system disorders Cytopenia	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Blood and lymphatic system disorders Sickle cell anaemia with crisis	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Cardiac disorders Acute myocardial infarction	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Cardiac disorders Cardiac arrest	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Ear and labyrinth disorders Vertigo positional	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Gastrointestinal disorders Abdominal pain	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Gastrointestinal disorders Diverticulum	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Gastrointestinal disorders Haemorrhoidal haemorrhage	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Gastrointestinal disorders Mouth ulceration	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Gastrointestinal disorders Small intestinal obstruction	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Gastrointestinal disorders Stomatitis	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Gastrointestinal disorders Tooth erosion	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
General disorders Chest pain	4.4% 2/45 • 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.	0.00% 0/12 • 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.	3.5% 2/57 • 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.
General disorders Gait disturbance	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
General disorders Multiple organ dysfunction syndrome	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
General disorders Pyrexia	2.2% 1/45 • 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.	8.3% 1/12 • 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.	3.5% 2/57 • 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.
Hepatobiliary disorders Cholelithiasis	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Hepatobiliary disorders Hypertransaminasaemia	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Hepatobiliary disorders Ischaemic hepatitis	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Immune system disorders Anaphylactic reaction	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Infections and infestations Appendicitis	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Infections and infestations Arthritis infective	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Infections and infestations COVID-19	6.7% 3/45 • 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.	8.3% 1/12 • 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.	7.0% 4/57 • 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.
Infections and infestations Cystitis	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Infections and infestations Device related bacteraemia	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Infections and infestations Endocarditis	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Infections and infestations Pneumonia	6.7% 3/45 • 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.	0.00% 0/12 • 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.	5.3% 3/57 • 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.
Infections and infestations Rhinovirus infection	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Infections and infestations Salmonella bacteraemia	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Infections and infestations Sepsis	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Infections and infestations Staphylococcal bacteraemia	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Infections and infestations Staphylococcal infection	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Infections and infestations Upper respiratory tract infection	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Infections and infestations Urinary tract infection	4.4% 2/45 • 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.	0.00% 0/12 • 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.	3.5% 2/57 • 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.
Infections and infestations Wound sepsis	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Injury, poisoning and procedural complications Gun shot wound	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Injury, poisoning and procedural complications Post-traumatic pain	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Injury, poisoning and procedural complications Tendon rupture	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.
Investigations SARS-CoV-2 test positive	2.2% 1/45 • 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.	0.00% 0/12 • 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.	1.8% 1/57 • 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.

Other adverse events
Measure	Crizanlizumab 5.0 mg/kg n=45 participants at risk Participants were administered crizanlizumab at a dose of 5.0 mg/kg by IV infusion.	Crizanlizumab 7.5 mg/kg n=12 participants at risk Participants were administered crizanlizumab at a dose of 7.5 mg/kg by IV infusion.	All Participants n=57 participants at risk Participants were administered either crizanlizumab at a dose of 5.0 mg/kg or at 7.5 mg/kg by IV infusion.
Cardiac disorders Supraventricular extrasystoles	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Cardiac disorders Tachycardia	2.2% 1/45 • 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.	8.3% 1/12 • 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.	3.5% 2/57 • 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.
Congenital, familial and genetic disorders Tornwaldt cyst	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Ear and labyrinth disorders Deafness neurosensory	4.4% 2/45 • 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.	8.3% 1/12 • 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.	5.3% 3/57 • 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.
Ear and labyrinth disorders Ear pain	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Ear and labyrinth disorders Tympanic membrane perforation	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Eye disorders Retinal detachment	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Eye disorders Retinal drusen	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Eye disorders Retinopathy sickle cell	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Gastrointestinal disorders Abdominal pain upper	6.7% 3/45 • 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.	0.00% 0/12 • 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.	5.3% 3/57 • 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.
Gastrointestinal disorders Constipation	6.7% 3/45 • 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.	16.7% 2/12 • 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.	8.8% 5/57 • 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.
Gastrointestinal disorders Diarrhoea	8.9% 4/45 • 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.	16.7% 2/12 • 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.	10.5% 6/57 • 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.
Gastrointestinal disorders Gastritis	6.7% 3/45 • 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.	0.00% 0/12 • 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.	5.3% 3/57 • 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.
Gastrointestinal disorders Nausea	13.3% 6/45 • 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.	16.7% 2/12 • 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.	14.0% 8/57 • 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.
Gastrointestinal disorders Pancreatitis	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Gastrointestinal disorders Toothache	8.9% 4/45 • 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.	0.00% 0/12 • 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.	7.0% 4/57 • 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.
Gastrointestinal disorders Vomiting	8.9% 4/45 • 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.	25.0% 3/12 • 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.	12.3% 7/57 • 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.
General disorders Chest pain	13.3% 6/45 • 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.	8.3% 1/12 • 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.	12.3% 7/57 • 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.
General disorders Drug withdrawal syndrome	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
General disorders Fatigue	8.9% 4/45 • 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.	8.3% 1/12 • 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.	8.8% 5/57 • 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.
General disorders Oedema peripheral	13.3% 6/45 • 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.	0.00% 0/12 • 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.	10.5% 6/57 • 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.
General disorders Pain	4.4% 2/45 • 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.	8.3% 1/12 • 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.	5.3% 3/57 • 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.
General disorders Peripheral swelling	2.2% 1/45 • 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.	8.3% 1/12 • 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.	3.5% 2/57 • 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.
General disorders Pyrexia	28.9% 13/45 • 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.	25.0% 3/12 • 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.	28.1% 16/57 • 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.
Hepatobiliary disorders Cholelithiasis	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Hepatobiliary disorders Ocular icterus	2.2% 1/45 • 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.	16.7% 2/12 • 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.	5.3% 3/57 • 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.
Infections and infestations Acute sinusitis	4.4% 2/45 • 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.	8.3% 1/12 • 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.	5.3% 3/57 • 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.
Infections and infestations COVID-19	11.1% 5/45 • 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.	16.7% 2/12 • 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.	12.3% 7/57 • 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.
Infections and infestations Cystitis	4.4% 2/45 • 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.	8.3% 1/12 • 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.	5.3% 3/57 • 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.
Infections and infestations Gastroenteritis	6.7% 3/45 • 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.	8.3% 1/12 • 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.	7.0% 4/57 • 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.
Infections and infestations Nasopharyngitis	2.2% 1/45 • 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.	8.3% 1/12 • 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.	3.5% 2/57 • 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.
Infections and infestations Otitis media acute	0.00% 0/45 • 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.	8.3% 1/12 • 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.	1.8% 1/57 • 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.
Infections and infestations Pharyngitis	8.9% 4/45 • 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.	8.3% 1/12 • 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.	8.8% 5/57 • 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.
Infections and infestations Pneumonia	4.4% 2/45 • 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.	8.3% 1/12 • 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.	5.3% 3/57 • 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.
Infections and infestations Tooth infection	6.7% 3/45 • 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.	0.00% 0/12 • 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.	5.3% 3/57 • 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.
Infections and infestations Upper respiratory tract infection	22.2% 10/45 • 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.	16.7% 2/12 • 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.	21.1% 12/57 • 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.
Infections and infestations Urinary tract infection	8.9% 4/45 • 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.	0.00% 0/12 • 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.	7.0% 4/57 • 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.
Injury, poisoning and procedural complications Post-traumatic pain	6.7% 3/45 • 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.	0.00% 0/12 • 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.	5.3% 3/57 • 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.
Injury, poisoning and procedural complications Road traffic accident	11.1% 5/45 • 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.	16.7% 2/12 • 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.	12.3% 7/57 • 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.
Injury, poisoning and procedural complications Skin laceration	4.4% 2/45 • 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.	8.3% 1/12 • 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.	5.3% 3/57 • 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.