Study of Dose Confirmation and Safety of Crizanlizumab in Pediatric Sickle Cell Disease Patients

Eligibility Criteria: Inclusion Criteria:

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

- Confirmed diagnosis of sickle cell disease (SCD) (e.g. any genotype including HbSS,
HbSC, HbSβ0-thalassemia, HbSβ+-thalassemia, and others) by hemoglobin electrophoresis
or high-performance liquid chromatography (HPLC) performed locally.

- Experienced at least 1 VOC within the preceding 12 months, as determined by medical
history. Prior VOC must have resolved at least 7 days prior to the first dose in the
study and should include all the following:

1. the occurrence of appropriate symptoms (see VOC definition in protocol Section
7.2.1.1)

2. either a visit to a medical facility or healthcare professional,

3. receipt of oral/parenteral opioid or other non-opioid parenteral analgesia.

- If receiving HU/HC or erythropoietin stimulating agent, must have been receiving the
drug for at least 6 months prior to Screening and plan to continue taking at the same
dose and schedule during the trial. Dose alterations of HU/HC during Part A are not
allowed, and if this occurs, the patient will enter directly to the Part B.

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

- Transcranial Doppler (TCD) considered low risk within the past 6 months (for 2 to 16
years).

Exclusion Criteria:

- History of stem cell transplant.

- Received any blood products within 30 days of Day 1 dosing.

- Participating in a chronic transfusion program (preplanned series of transfusions for
prophylactic purposes).

- Patients with bleeding disorders

- Planning on undergoing an exchange transfusion during the duration of the study.
Patients requiring episodic transfusion in response to worsened anemia or VOC are
permitted.

- Contraindication or hypersensitivity to any drug from similar class as study drug or
to any excipients of the study drug formulation.

- Received a monoclonal antibody or immunoglobulin-based therapy within 6 months of
Screening, or has documented immunogenicity to a prior monoclonal antibody.

- Received active treatment on another investigational trial within 30 days (or 5 half
lives of that agent, whichever is greater) prior to Screening or plans to participate
in another investigational drug trial.

- Pregnant females or females who have given birth within the past 90 days or who are
breastfeeding.

- Any documented history of a stroke or intracranial hemorrhage, or an uninvestigated
neurologic finding within the past 12 months

- Any conditional TCD within the past 12 months

- Use of therapeutic anticoagulation (prophylactic doses permitted) or antiplatelet
therapy (other than aspirin) within the 10 days prior to Week 1 Day 1 dosing

- Hospitalized at Screening

- Planning to undergo a major surgical procedure during the duration of the study

- Planning to initiate or terminate HU/HC while on study, other than for safety reasons

- Patient with active HIV infection (detectable viral load)

- Patients with known active Hepatitis B infection.

- Patients with known Hepatitis C history.

- Significant active infection or immune deficiency (including chronic use of
immunosuppressive drugs) in the opinion of the investigator.

- Malignant disease. Exceptions to this exclusion include the following: malignancies
that were treated curatively and have not recurred within 2 years prior to study
treatment; any completely resected carcinoma in situ.

- Has a serious mental or physical illness, which, in the opinion of the Investigator
would compromise participation in the study.

- Resting QTcF ≥450 msec at pretreatment (baseline) for patients under 12 years of age
and ≥450 msec for males and ≥460 msec for female patients 12 years and older.

- Cardiac or cardiac repolarization abnormality

- Long QT syndrome, family history of idiopathic sudden death or congenital long QT
syndrome

- Sexually active females who are unwilling to comply with reliable method of birth
control until 15 weeks following last dose of study drug.

- Current drug or alcohol abuse:

1. Has a positive qualitative urine drug test at Screening for cocaine,
phencyclidine (PCP), or amphetamines (opioids are permitted).

2. Consumes >12 (for males) or >8 (for females) standard alcoholic beverages per
week.

- Not able to understand and to comply with study instructions and requirements.

- Subjects, who are an employee of the sponsor or investigator or otherwise dependent on
them.

- Subjects, who are committed to an institution by virtue of an order issued either by
the judicial or the administrative authorities.