A Phase III, multicenter, randomized, double-blind study to assess efficacy and safety of two doses of crizanlizumab versus placebo, with or without hydroxyureal/hydroxycarbamide therapy, in adolescent and adult sickle cell disease patients with vaso-occlusive crises (STAND)

1. Written informed consent must be obtained prior to any screening procedures
2. Male or female patients aged 12 years and older on the day of signing
informed consent.
3. Confirmed diagnosis of SCD by Hb electrophoresis or HPLC (performed
locally). All SCD genotypes are eligible, genotyping is not required for study
entry,
4. Experienced at least 2 VOCs leading to healthcare visit within the 12 months
prior to screening visit as determined by medical history. Prior VOC leading to
healthcare visit must resolve at least 7 days prior to Week 1 Day 1 and must
include:
a. Pain crisis defined as an acute onset of pain for which there is no other
medically determined explanation other than vaso- occlusion
b. a visit to a medical facility and/or healthcare professional,
c. and receipt of oral/parenteral opioids or parenteral nonsteroidal
antiinflammatory drug (NSAID) analgesia,
Acute chest syndrome (ACS), priapism and hepatic or splenic sequestration will
be considered VOC in this study.

5. If receiving HU/HC or erythropoietin stimulating agent or L-glutamine, must
have been receiving the drug for at least 6 months prior to screening visit and
plan to continue taking at the same dose and schedule until the subject has
reached one year of study treatment,
6. Patients must meet the following central laboratory values at the screening
visit:
* Absolute Neutrophil Count >=1.0 x 109/L
* Platelet count >=75 x 109/L
* Hemoglobin: for adults (Hb) >=4.0 g/dL and for adolescents (Hb) >=5.5 g/dL
* Glomerular filtration rate >= 45 mL/min/1.73 m2 using CKD-EPI formula in
adults, and Schwartz formula in adolescents
* Direct (conjugated) bilirubin < 2.0 x ULN
* Alanine transaminase (ALT) < 3.0 x ULN, 7. ECOG performance status <=2.0 for
adults and Karnofsky >= 50% for adolescents

1. History of stem cell transplant.
2. Participating in a chronic transfusion program (pre-planned series of
transfusions for prophylactic purposes) and/or planning on undergoing an
exchange
transfusion during the duration of the study; episodic transfusion in response
to worsened anemia or VOC is permitted., 3. Contraindication or
hypersensitivity to any drug or metabolites from similar class as study drug or
to any excipients of the study drug formulation.
4. Received active treatment on another investigational trial within 30 days
(or 5 half-lives of that agent, whichever is greater) prior to Screening visit
or plans to
participate in another investigational drug trial., 5. Women of child-bearing
potential, defined as all women physiologically capable of becoming pregnant
unless they are using highly effective methods of
contraception during dosing and for 15 weeks after stopping treatment.
6. Concurrent severe and/or uncontrolled medical conditions which, in the
opinion of the Investigator, could cause unacceptable safety risks or compromise
participation in the study.
7. History or current diagnosis of ECG abnormalities indicating significant
risk of safety
8. Not able to understand and to comply with study instructions and
requirements.