Trial Outcomes & Findings for Study of Two Doses of Crizanlizumab Versus Placebo in Adolescent and Adult Sickle Cell Disease Patients (NCT NCT03814746)

Last Updated: 2026-01-30

Results Overview

VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Healthcare visit is defined as any visit to a medical facility such as emergency room (ER), hospital and/or office visit, which includes pain management of VOC in situ. Annualized rate of corresponding VOC events = (Number of corresponding VOC events \* 365)/(number of days in the observation period). Observation period = time from date of randomization to 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 therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days).

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

255 participants

Primary outcome timeframe

1 year

Results posted on

2026-01-30

Participant Flow

240 participants (including 48 adolescents) were planned to be randomized in a 1:1:1 ratio to either 5 mg/kg, 7.5 mg/kg of crizanlizumab or placebo. This study was conducted in 21 countries and 63 centers.

Screening assessments were done within 1 to 28 days prior to Week 1 Day 1. Re-screening of subjects was only allowed if the subject was not randomized before.

Participant milestones

Participant milestones
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo Participants received 0.5mL/kg placebo drug by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Overall Study STARTED	84	83	85
Overall Study COMPLETED	66	68	58
Overall Study NOT COMPLETED	18	15	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo Participants received 0.5mL/kg placebo drug by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Overall Study Participant decision	9	6	15
Overall Study Physician Decision	2	2	4
Overall Study Death	2	2	2
Overall Study Adverse Event	2	2	1
Overall Study Lost to Follow-up	2	1	2
Overall Study Unsatisfactory therapeutic effect	0	1	2
Overall Study Pregnancy	0	1	1
Overall Study Protocol Violation	1	0	0

Baseline Characteristics

Study of Two Doses of Crizanlizumab Versus Placebo in Adolescent and Adult Sickle Cell Disease Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=84 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=83 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo n=85 Participants Participants received 0.5mL/kg placebo drug by IV infusions on day 1, day 15 and every 4 weeks thereafter.	Total n=252 Participants Total of all reporting groups
Age, Customized Adolescents, 12 - < 18 years	16 participants n=35 Participants	18 participants n=4328 Participants	20 participants n=8687 Participants	54 participants n=269 Participants
Age, Customized 18 - < 65 years	68 participants n=35 Participants	65 participants n=4328 Participants	63 participants n=8687 Participants	196 participants n=269 Participants
Age, Customized 65 - < 85 years	0 participants n=35 Participants	0 participants n=4328 Participants	2 participants n=8687 Participants	2 participants n=269 Participants
Sex: Female, Male Female	45 Participants n=35 Participants	45 Participants n=4328 Participants	49 Participants n=8687 Participants	139 Participants n=269 Participants
Sex: Female, Male Male	39 Participants n=35 Participants	38 Participants n=4328 Participants	36 Participants n=8687 Participants	113 Participants n=269 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	22 Participants n=35 Participants	20 Participants n=4328 Participants	18 Participants n=8687 Participants	60 Participants n=269 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	54 Participants n=35 Participants	56 Participants n=4328 Participants	57 Participants n=8687 Participants	167 Participants n=269 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=35 Participants	7 Participants n=4328 Participants	10 Participants n=8687 Participants	25 Participants n=269 Participants
Race/Ethnicity, Customized Black or African American	46 Participants n=35 Participants	34 Participants n=4328 Participants	43 Participants n=8687 Participants	123 Participants n=269 Participants
Race/Ethnicity, Customized White	27 Participants n=35 Participants	31 Participants n=4328 Participants	26 Participants n=8687 Participants	84 Participants n=269 Participants
Race/Ethnicity, Customized Asian	6 Participants n=35 Participants	7 Participants n=4328 Participants	6 Participants n=8687 Participants	19 Participants n=269 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	3 Participants n=35 Participants	7 Participants n=4328 Participants	6 Participants n=8687 Participants	16 Participants n=269 Participants
Race/Ethnicity, Customized Multiple (White and Black or African American)	1 Participants n=35 Participants	0 Participants n=4328 Participants	0 Participants n=8687 Participants	1 Participants n=269 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=35 Participants	4 Participants n=4328 Participants	4 Participants n=8687 Participants	9 Participants n=269 Participants

PRIMARY outcome

Timeframe: 1 year

Population: The FAS comprises all participants to whom study treatment has been assigned by randomization.

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=84 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=83 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo n=85 Participants Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Annualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to a Healthcare Visit	2.5 number of events per year Standard Deviation 2.98	1.9 number of events per year Standard Deviation 2.30	2.1 number of events per year Standard Deviation 2.81

SECONDARY outcome

Timeframe: 1 year

Population: The FAS comprises all participants to whom study treatment has been assigned by randomization.

VOCs are based on documentation by provider following contact with participant. VOC:pain crisis requiring therapy with oral/parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome, priapism and hepatic or splenic sequestration. Healthcare visit:a visit to a medical facility (ER, hospital \&/or office visit resulting in pain management of VOC. Managed at home: no visit to any medical facility \&/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice is allowed. Annualized rate of corresponding VOC events = (# of corresponding VOC events \* 365)/(# of days in observation period). Observation period = time from date of randomization to 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 \& erythropoietin therapies to treat SCD \&/or to prevent/reduce VOCs), date of randomization + 365 days)

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=84 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=83 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo n=85 Participants Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Annualized Rate of All VOCs Leading to a Healthcare Visit and Treated at Home Over the First-year Post Randomization (Key Secondary)	4.5 number of events per year Standard Deviation 6.49	3.1 number of events per year Standard Deviation 2.89	3.7 number of events per year Standard Deviation 3.78

SECONDARY outcome

Timeframe: 5 years

To compare the efficacy of 5.0 mg/kg vs placebo \& 7.5 mg/kg vs placebo on the annualized rate of all VOCs based on documentation by provider following contact with participant. VOC is defined as pain crisis (an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) requiring therapy with oral/parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome, priapism and hepatic or splenic sequestration. Healthcare visit is defined as a visit to a medical facility (emergency room, hospital and/or office visit resulting in pain management of VOC. Managed at home is defined as no visit to any medical facility and/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice is allowed. The annualized rate of VOC leading to healthcare visit is the number of VOC leading to healthcare visit multiplied by 365 \& divided by the number of days in observation period.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

Population: The FAS comprises all participants to whom study treatment has been assigned by randomization. Participants with no VOC leading to healthcare visits are excluded.

To assess the duration of VOCs leading to healthcare visit in each group. Mean duration of VOC per participant is defined as the average duration of all individual episodes of VOCs leading to healthcare visits of a given participant (a VOC duration is defined as end date of the VOC - start date of the VOC + 1). Participants with no VOC leading to healthcare visits have been excluded.

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=59 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=52 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo n=51 Participants Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Mean Duration of VOCs Leading to a Healthcare Visit Over the First-year Post Randomization	7.7 days Standard Deviation 6.93	6.0 days Standard Deviation 4.54	6.6 days Standard Deviation 5.55

SECONDARY outcome

Timeframe: 1 year

Population: The FAS comprises all participants to whom study treatment has been assigned by randomization.

To assess the number of participants free from VOCs leading to healthcare visit. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. A participant is free from VOC if they do not have a VOC crisis.

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=84 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=83 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo n=85 Participants Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Number of Participants Free From VOCs Leading to a Healthcare Visit Over the First-year Post Randomization	25 Participants	31 Participants	34 Participants

SECONDARY outcome

Timeframe: 1 year

Population: The FAS comprises all participants to whom study treatment has been assigned by randomization.

To assess the percentage of participants free from VOCs leading to healthcare visit. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. A participant is free from VOC if they do not have a VOC crisis.

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=84 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=83 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo n=85 Participants Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Percentage of Participants Free From VOCs Leading to a Healthcare Visit Over the First-year Post Randomization	29.8 Percentage of participants	37.3 Percentage of participants	40.0 Percentage of participants

SECONDARY outcome

Timeframe: 1 year

Population: The FAS comprises all participants to whom study treatment has been assigned by randomization. The estimated time to first and second VOC using Kaplan-Meier analyzed all participants, including those who experienced first (n=59, 52, 51) and second (n=41, 33, 33) events in 5mg/kg, 7.5mg/kg and placebo arms, respectively, those who were at risk, and those who were censored.

To assess the time to first and second VOC leading to healthcare visit in each group. Time to first occurrence of VOC leading to a healthcare visit is defined as the time from the date of randomization to the date of the first occurrence of the VOC. Time to second occurrence of VOC leading to a healthcare visit is defined as the time from date of randomization to the date of the second occurrence of VOC.

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=84 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=83 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo n=85 Participants Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Time to First and Second VOCs Leading to a Healthcare Visit Over the First-year Post Randomization Time to first occurrence of VOC	3.9 Months Interval 2.4 to 6.0	6.2 Months Interval 3.2 to 10.3	6.2 Months Interval 2.8 to 11.9
Time to First and Second VOCs Leading to a Healthcare Visit Over the First-year Post Randomization Time to second occurrence of VOC	10.6 Months Interval 7.7 to NA: there were not enough patients or/and events to estimate the upper limit of CI	NA Months Interval 10.2 to NA: there were not enough patients or/and events to estimate the median and upper limit of CI	NA Months Interval 8.9 to NA: there were not enough patients or/and events to estimate the median and upper limit of CI

SECONDARY outcome

Timeframe: 1 year

Population: The FAS comprises all participants to whom study treatment has been assigned by randomization.

To assess Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) both overall and VOC-related in each group. Annualized rate of corresponding healthcare visits =(Number of corresponding healthcare visits \* 365)/(number of days in the observation period). Observation period = time from date of randomization to 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 therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days)

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=84 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=83 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo n=85 Participants Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Annualized Rate of Visits to Clinic, Emergency Room (ER) and Hospitalizations, Both Overall and VOC-related Over the First-year Post-randomization Annualized rate of all clinic, hospitalizations and ER visits	3.5 number of events per year Standard Deviation 3.65	2.6 number of events per year Standard Deviation 3.21	3.0 number of events per year Standard Deviation 3.87
Annualized Rate of Visits to Clinic, Emergency Room (ER) and Hospitalizations, Both Overall and VOC-related Over the First-year Post-randomization Annualized rate of VOC-related clinic, hospitalizations and ER visits	3.0 number of events per year Standard Deviation 3.52	2.2 number of events per year Standard Deviation 3.01	2.5 number of events per year Standard Deviation 3.53

SECONDARY outcome

Timeframe: 1 year

Population: The FAS comprises all participants to whom study treatment has been assigned by randomization.

To assess Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) both overall and VOC-related in each group. Annualized days of corresponding healthcare visits =(Number of days =(Number of days of corresponding healthcare visits \* 365)/(number of days in the observation period). Observation period = time from date of randomization to 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 therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days).

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=84 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=83 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo n=85 Participants Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Annualized Days of Visits to Clinic, Emergency Room (ER) and Hospitalizations, Both Overall and VOC-related Over the First-year Post-randomization Annualized days of all clinic, hospitalizations and ER visits	17.6 number of days per year Standard Deviation 27.80	11.3 number of days per year Standard Deviation 14.29	12.9 number of days per year Standard Deviation 18.32
Annualized Days of Visits to Clinic, Emergency Room (ER) and Hospitalizations, Both Overall and VOC-related Over the First-year Post-randomization Annualized days of all VOC-related clinic, hospitalizations and ER visits	13.8 number of days per year Standard Deviation 18.12	9.3 number of days per year Standard Deviation 12.62	11.3 number of days per year Standard Deviation 18.35

SECONDARY outcome

Timeframe: Over first year post-randomization (Baseline, Week 27 Day 1, Week 51 Day 1)

Population: The FAS comprises all participants to whom study treatment has been assigned by randomization.

Laboratory values for parameters related to renal function (creatinine, estimated glomerular filtration rate, urine microalbumin, and urine albumin/creatinine ratio) were measured at 6-month intervals over time from baseline.

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=84 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=83 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo n=85 Participants Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Evolution of Albumin Creatinine Ratio (ACR) Over the First-year Post-randomization (Change From Baseline) Chage from baseline at Week 51 Day 1	0.1 g/mol Interval -34.0 to 187.0	-0.1 g/mol Interval -103.0 to 49.0	-0.2 g/mol Interval -21.0 to 59.0
Evolution of Albumin Creatinine Ratio (ACR) Over the First-year Post-randomization (Change From Baseline) Change from baseline at Week 27 Day 1	0.1 g/mol Interval -30.0 to 96.0	-0.0 g/mol Interval -157.0 to 28.0	-0.1 g/mol Interval -20.0 to 40.0

SECONDARY outcome

Timeframe: Over first year post-randomization (Baseline, Week 27 Day 1, Week 51 Day 1)

Population: The FAS comprises all participants to whom study treatment has been assigned by randomization.

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=84 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=83 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo n=85 Participants Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Evolution of Albuminuria (Urine Microalbumin) Over the First-year Post-randomization (Change From Baseline) Change from baseline at Week 27 Day 1	0.0 g/L Interval -1.0 to 1.0	0.0 g/L Interval -1.0 to 0.0	0.0 g/L Interval 0.0 to 0.0
Evolution of Albuminuria (Urine Microalbumin) Over the First-year Post-randomization (Change From Baseline) Change from baseline at Week 51 Day 1	0.0 g/L Interval -1.0 to 1.0	0.0 g/L Interval -1.0 to 1.0	0.0 g/L Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: AUCd15 (first-dose) was assessed at W1D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose) to W3D1; AUCtau (steady-state) was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1

Population: Pharmacokinetic analysis set 1 includes all participants who provided at least one evaluable PK profile: received the planned treatment at 5 mg/kg or 7.5 mg/kg before single dose PK profile or 3 consecutive doses of the planned treatment before the multiple dose PK profile for the multiple dose PK profile; provided at least one PK parameter; did not have any transfusion of blood product in the last 4 weeks before the first PK sample of the full PK profile, or during the full PK profile.

To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: Area under the (concentration-time profile) curve.

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=76 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=75 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Pharmacokinetic (PK) Profile of Crizanlizumab: AUCd15, AUCtau AUCd15 (first dose)	11300 hr*ug/mL Standard Deviation 2950	17000 hr*ug/mL Standard Deviation 4100	—
Pharmacokinetic (PK) Profile of Crizanlizumab: AUCd15, AUCtau AUCtau (steady state)	18800 hr*ug/mL Standard Deviation 5470	30200 hr*ug/mL Standard Deviation 8580	—

SECONDARY outcome

Timeframe: first-dose was assessed at W1D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose) through to W3D1; steady-state was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1

To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: Maximum concentration.

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=76 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=75 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
PK Profile of Crizanlizumab: Cmax Cmax (first dose)	95.9 ug/mL Standard Deviation 29.4	143 ug/mL Standard Deviation 45.3	—
PK Profile of Crizanlizumab: Cmax Cmax (steady state)	108 ug/mL Standard Deviation 60.2	162 ug/mL Standard Deviation 57.4	—

SECONDARY outcome

To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: Time to maximum concentration.

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=76 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=75 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
PK Profile of Crizanlizumab: Tmax Tmax (first dose)	2.08 hr Interval 0.467 to 25.5	2.08 hr Interval 0.5 to 24.2	—
PK Profile of Crizanlizumab: Tmax Tmax (steady state)	2.00 hr Interval 0.25 to 24.9	3.58 hr Interval 0.5 to 24.9	—

SECONDARY outcome

Timeframe: steady-state was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1

To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: half life.

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=43 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=43 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
PK Profile of Crizanlizumab: Half-life	9.51 day Standard Deviation 3.67	11.2 day Standard Deviation 3.55	—

SECONDARY outcome

Timeframe: AUCd15 (first dose): W1D1, W1D2, W1D4, W2D1 and W3D1; steady state: W15D1, W15D2, W15D4, W16D1, W17D1 W18D1 and W19D1

Population: The Pharmacodynamic analysis set 1 includes all participants who provided at least 1 evaluable PD profile: received planned treatment of crizanlizumab at 5 mg/kg or 7.5 mg/kg before single dose PD profile or 3 consecutive doses of planned treatment before the multiple dose PD profile; provided at least 1 PD-AUC (single dose or multiple dose) parameter; did not have any transfusion of blood product in the last 4 weeks before the first PD sample of the full PD profile or during the full PD profile

To characterize the pharmacodynamic (PD) of crizanlizumab at 5.0 and 7.5 mg/kg: P-selectin inhibition (% inhibition multipled by hr)

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=61 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=63 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
PD Parameter (P-selectin Inhibition) PD-AUCd29 (steady state)	65100 h * % Standard Deviation 7000	66100 h * % Standard Deviation 7190	—
PD Parameter (P-selectin Inhibition) PD-AUCd15 (first dose)	32700 h * % Standard Deviation 3830	33100 h * % Standard Deviation 3530	—

SECONDARY outcome

Timeframe: 1 year

Population: The FAS comprises all participants to whom study treatment has been assigned by randomization.

To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOCs leading to healthcare visit. VOC is defined as pain crisis which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Healthcare visit: any visit to a medical facility such as ER, hospital and/or office visit, which includes pain management of VOC in situ. Annualized rate of corresponding VOC events = (Number of corresponding VOC events \* 365)/(number of days in the observation period). Observation period = time from date of randomization to 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 therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days).

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=84 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=83 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo n=85 Participants Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Annualized Rate of Various Subtypes of VOCs Leading to a Healthcare Visit at 1 Year Subtype of VOC: Uncomplicated sickle cell-vaso-occlusive crisis	2.3 number of events per year Standard Deviation 2.74	1.8 number of events per year Standard Deviation 2.27	2.0 number of events per year Standard Deviation 2.79
Annualized Rate of Various Subtypes of VOCs Leading to a Healthcare Visit at 1 Year Subtype of VOC: Acute chest syndrome	0.2 number of events per year Standard Deviation 1.44	0.0 number of events per year Standard Deviation 0.21	0.1 number of events per year Standard Deviation 0.44
Annualized Rate of Various Subtypes of VOCs Leading to a Healthcare Visit at 1 Year Subtype of VOC: Hepatic sequestration	0.0 number of events per year Standard Deviation 0.00	0.0 number of events per year Standard Deviation 0.00	0.0 number of events per year Standard Deviation 0.00
Annualized Rate of Various Subtypes of VOCs Leading to a Healthcare Visit at 1 Year Subtype of VOC: Splenic sequestration	0.0 number of events per year Standard Deviation 0.00	0.0 number of events per year Standard Deviation 0.11	0.0 number of events per year Standard Deviation 0.00
Annualized Rate of Various Subtypes of VOCs Leading to a Healthcare Visit at 1 Year Subtype of VOC: Priapism	0.0 number of events per year Standard Deviation 0.00	0.0 number of events per year Standard Deviation 0.15	0.0 number of events per year Standard Deviation 0.11

SECONDARY outcome

Timeframe: 5 years

To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOCs leading to healthcare visit. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Healthcare visit is defined as any visit to a medical facility such as emergency room, hospital and/or office visit, which includes pain management of VOC in situ. The annualized rate of VOC leading to healthcare visit is the number of VOC leading to healthcare visit multiplied by 365 and divided by the number of days in the observation period.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 5 years

To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the rates of all VOCs (managed at home + leading to healthcare visit).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

Population: The FAS comprises all participants to whom study treatment has been assigned by randomization.

To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the number of VOC events that were managed at home. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Managed at home is defined as no visit to any medical facility and/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice was allowed.

Outcome measures

Outcome measures
Measure	Crizanlizumab (SEG101) at 5.0 mg/kg n=84 Participants Participants received Crizanlizumab (SEG101) 5.0 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Crizanlizumab (SEG101) at 7.5 mg/kg n=83 Participants Participants received Crizanlizumab (SEG101) 7.5 mg/kg IV infusions on day 1, day 15 and every 4 weeks thereafter.	Placebo n=85 Participants Participants received 0.5mL/kg placebo by IV infusions on day 1, day 15 and every 4 weeks thereafter.
Number of VOCs Managed at Home at Year 1	163 total number of VOC events	106 total number of VOC events	129 total number of VOC events

SECONDARY outcome

Timeframe: 5 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 5 years

To assess safety of crizanlizumab over the study period.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 5 years

To assess safety of crizanlizumab over the study period.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 5 years

To assess immunogenicity of crizanlizumab over the study period.

Outcome measures

Outcome data not reported

Adverse Events

Crizanlizumab (SEG101) at 5.0 mg/kg (On-treatment)

Serious events: 35 serious events

Other events: 67 other events

Deaths: 2 deaths

Crizanlizumab (SEG101) at 7.5 mg/kg (On-treatment)

Serious events: 22 serious events

Other events: 71 other events

Deaths: 2 deaths

Placebo (On-treatment)

Serious events: 26 serious events

Other events: 66 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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER