The purpose of the Phase 2 CSEG101B2201 study is to confirm and to establish appropriate
dosing and to evaluate the safety in pediatric participants ages 6 months to <18 years
with a history of VOC with or without HU/HC, receiving crizanlizumab for 2 years. The
efficacy and safety of crizanlizumab was already demonstrated in adults with sickle cell
disease. The approach is to extrapolate from the PK/pharmacodynamics (PD) already
established in the adult population. The study is designed as a Phase II, multicenter,
open-label study

1. Male or female patients ages 2 to <18 years (Group 3 will be expanded to allow
enrolment of patients ages 6 to <24 months (and at least 7 kg) in Part B once the
appropriate dose is confirmed in 2 to <6 year old participants).

2. Confirmed diagnosis of SCD (any genotype including HbSS, HbSC, HbSβ0-thalassemia,
HbSβ+-thalassemia patients, and others) by hemoglobin electrophoresis or/and
high-performance liquid chromatography (HPLC) [performed locally]. Confirmation of
diagnosis by two accepted methods is recommended.

3. Experienced at least 1 VOC within the preceding 12 months prior to screening, as
determined by medical history. Prior VOC must have resolved at least 7 days prior to
the first dose in the study and must include all the following: a.the occurrence of
appropriate symptoms (see VOC definition in Section 7.2.1.1), b.either a visit to a
medical facility or healthcare professional, c.receipt of oral/parenteral opioid or
parenteral NSAIDs

4. If receiving HU/HC, L-glutamine or erythropoietin stimulating agent, must have been
receiving the drug consistently for at least 6 months prior to screening and plan to
continue taking it at the same dose and schedule during the trial. Patients who have
not been receiving such drugs must have been off them for at least 6 months prior to
screening. . Dose alterations of HU/HC, L-glutamine or erythropoietin stimulating
agent during Part A are not allowed, and if this occurs, the participant will enter
directly to Part B.

5. Received standard age-appropriate care for SCD, including penicillin prophylaxis,
pneumococcal immunization, and parental education.

6. Performance status: Karnofsky ≥ 50% for patients >10 years of age, and Lansky ≥ 50
for patients ≤ 10 years of age.

7. Patient must meet the following laboratory values prior to Week 1 Day 1: Absolute
Neutrophil Count ≥1.0 x 109/L , Platelets ≥75 x 109/L, Hemoglobin (Hgb) > 5.5 g/dL

8. Patient must have adequate renal and hepatic function as defined:Estimated
Glomerular filtration rate (eGFR) ≥ 75 mL/min/1.73 m2 using Schwartz formula, Direct
(conjugated) bilirubin ≤ 2.0 x ULN, Alanine transaminase (ALT) ≤ 3.0 x ULN,

9. Transcranial Doppler (TCD) for patients aged 2 to < 16 years at time of screening,
with HbSS, HbSβ0-thalassemia, and HbSD disease indicating low risk for stroke (per
investigator). Please refer to Section 7.2.2.6 for details

10. Written informed consent/assent, according to local guidelines, signed by the
patient and / or by the parents or legal guardian prior to any study related
screening procedures are performed.

11. Female of non-childbearing potential or with negative serum pregnancy test on
Screening and a negative urine pregnancy test (dipstick) prior to dosing on Day 1.