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 include
participants aged 18 years and older.

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

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

4. If the participant is on HU/HC, they must be taking it for at least 6 months and at
stable dose for at least 3 months prior to the Screening visit and plan to continue
taking 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 6-12
months prior to the screening visit must have evidence of insufficient control of
acute pain despite initiation. These participants must have a cumulative of 4-12
VOCs 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, the
participant must have been receiving the drug for at least 6 months prior to
screening visit and plan to continue taking the drug at the same dose and schedule
until 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 to
management at a health care facility or those managed via remote consultation)
within the 12 months prior to screening visit as determined by medical history and
documented 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 an
uninvestigated 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 transfusions
for prophylactic purposes) and/or planning to undergo an exchange transfusion during
the duration of the study; episodic transfusion in response to worsened anemia or
VOC is permitted.

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