A Study to Investigate the Efficacy and Safety of Crizanlizumab (5 mg/kg) Compared With Placebo in Adolescent and Adult Sickle Cell Disease Patients Who Experience Frequent Vaso-Occlusive Crises (SPARKLE)

Key Inclusion Criteria:

1. Participants must be aged 12 years and older on the day of signing informed consent.Adolescents include participants aged 12 to <18 years old and adults includeparticipants aged 18 years and older.

2. Confirmed diagnosis of SCD by Hb electrophoresis or high-performance liquidchromatography (HPLC) (performed locally or by central laboratory if not availablelocally). All SCD genotypes are eligible.

3. Experienced 4 to 12 VOCs (refer to Section 8.3.1 for study definition of VOC) thatare HCP-managed (including VOCs leading to management at a health care facility orthose managed via remote consultation) within the 12 months prior to the screeningvisit. Baseline VOCs are determined by medical history and are required to bedocumented at source.

4. If the participant is on HU/HC, they must be taking it for at least 6 months and atstable dose for at least 3 months prior to the Screening visit and plan to continuetaking it at the same dose and schedule until at least the participant has reached 52 weeks of the planned study treatment. Participants who have initiated HU/HC 6-12months prior to the screening visit must have evidence of insufficient control ofacute pain despite initiation. These participants must have a cumulative of 4-12VOCs in the 12 months prior to the screening period, with at least 2 during the last 6 months while on HU/HC. If receiving erythropoietin stimulating agent, theparticipant must have been receiving the drug for at least 6 months prior toscreening visit and plan to continue taking the drug at the same dose and scheduleuntil the participant has reached 52 weeks of the planned study treatment.

Participants who have not been receiving HU/HC, and/or erythropoietin stimulating agent must not have received it for at least 6 months prior to screening visit.

Key Exclusion Criteria:

1. Fewer than 4 or more than 12 VOCs that are HCP-managed (including VOCs leading tomanagement at a health care facility or those managed via remote consultation)within the 12 months prior to screening visit as determined by medical history anddocumented at source.

2. History of stem cell transplant and/or gene therapy.

3. Received blood products within 30 days prior to Week 1 Day 1 dosing.

4. Any documented history of a clinical stroke or intracranial hemorrhage, or anuninvestigated neurologic finding within the past 12 months before screening visit.Silent infarct only present on imaging is not excluded.

5. Participating in a chronic transfusion program (pre-planned series of transfusionsfor prophylactic purposes) and/or planning to undergo an exchange transfusion duringthe duration of the study; episodic transfusion in response to worsened anemia orVOC is permitted.

6. Contraindication or hypersensitivity to any drug or metabolites from similar classas study drug or to any excipients of the study drug formulation. History of severehypersensitivity reaction to other monoclonal antibodies, which in the opinion ofthe investigator may pose an increased risk of serious infusion reaction.