A Pharmacokinetic (PK) and Pharmacodynamic (PD) Dose-ranging Phase II Study of Ticagrelor in Paediatric Patients With Sickle Cell Disease

This is a multicenter, open-label, dose-ranging study of ticagrelor followed by a double
blind, placebo-controlled extension phase in paediatric patients with sickle cell disease
(SCD).

Part A: Patients will be randomised 1:1 to receive one of two dosing schedules consisting of
two single weight-adjusted doses of ticagrelor. Pharmacokinetic (PK) parameters and
pharmacodynamic (PD) measurements will be determined following each dose. Platelet
aggregation will be measured using the VerifyNow™ P2Y12 assay.

Following these 2 single doses, all patients will receive open-label one-week treatment with
ticagrelor twice daily to determine tolerability prior to randomisation into Part B.

Part B: In this part patients will be randomised (2:1 ratio) to ticagrelor twice daily or
placebo for a 4-week treatment phase.

During the study, patients will be followed for the occurrence of vaso-occlusive crisis (VOC)
and for other disease manifestations such as daily pain, analgesic use and complications of
SCD.

Inclusion criteria

- Children aged ≥2 to <18 years of age

- Diagnosed with homozygous sickle cell (HbSS) or sickle beta-zero-thalassaemia (HbS/β0)

Exclusion criteria

- At risk for haemorrhagic or bradycardic events

- Significant hepatic impairment

- Renal failure requiring dialysis

- Concomitant oral or intravenous therapy with strong CYP3A4 (cytochrome) inhibitors,
CYP3A4 substrates with narrow therapeutic indices, or strong CYP3A4 inducers.

- Surgical procedure planned to occur during the study.

- Patients who are currently pregnant or breastfeeding or planning to become pregnant
during the study.

- Patients who have known hypersensitivity or contraindication to ticagrelor.