A Study to Assess the Effect of Ticagrelor in Reducing the Number of Days With Pain in Patients With Sickle Cell Disease

This is a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, study
evaluating 2 doses of ticagrelor in 90 patients aged 18 to 30 years, with sickle cell disease
(SCD). Patients will be randomised to double-blind double-dummy treatment period in a 1:1:1
ratio (30 to each treatment group) to receive ticagrelor 10 mg twice daily (bid), or
ticagrelor 45 mg bid, or placebo bid to determine the frequency of days with pain using an
electronic diary (eDiary) every day. Approximately 180 patients will be enrolled. Patient
will be followed for safety assessment during and after 2 weeks of treatment completion.

During the 16 week treatment period, patients will complete a daily eDiary concerning daily
pain intensity, pain location, use of analgesics and absence from school or work. At the end
of the study patients will be asked to rate the change in their sickle cell pain compared to
the start of treatment. Platelet aggregation will be measured and reported as P2Y12 reaction
units (PRU) pre-dose and 2 hours post-dose at week 4 and week 5 after treatment start.
Pharmacokinetic (PK) parameters will be measured at 2 hours post-dose at week 4, and pre-dose
and at 2 hours post-dose at week 5. Biomarkers will be assessed pre-dose at week 4, week 5
and week 8. During the study, patients will be evaluated for adverse events (AEs) including
bleeding and vaso-occlusive crisis (VOC).

Inclusion Criteria:

- Confirmed medical history or diagnosis of homozygous sickle cell (HbSS) or sickle
beta-zero-thalassaemia (HbS/β0) by HPLC

- If treated with hydroxyurea, the dose must have been stable for 3 months

Exclusion Criteria:

- History of transient ischaemic attack or clinically overt cerebrovascular accident

- Moderate or severe hepatic impairment

- Treatment with chronic red blood cell transfusion therapy

- Pre-dominate cause of pain is not sickle cell disease related

- Chronic treatment with anticoagulants or antiplatelet drugs.