Haematological Disorders
Conditions
Interventions
Ticagrelor
Placebo
Sponsors
AstraZeneca
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed and dated informed consent prior to any study specific procedures not part of standard medical care (local regulations and international guidelines are to be followed in determining the assent/consent requirements for children). 2. Male or female paediatric patients aged =2 to <18 years and body weight of =12 kg (at Visit 1), diagnosed with HbSS or HbS/ß0 as confirmed by highperformance liquid chromatography or haemoglobin electrophoresis. Note: Diagnosis of SCD (if not confirmed prior to screening and records available on the medical file) should be confirmed for HbSS or HbS/ß0 by high-performance liquid chromatography or haemoglobin electrophoresis, performed at the site’s local lab, in order to confirm the type of mutation. 3. Have experienced at least 2 VOCs (painful crisis and/or ACS) as judged by the Investigator in the past 12 months prior to Visit 1. These VOCs need to be documented in the patient’s medical records or in other documents that can be reconciled. 4. If =16 years old, must have had transcranial Doppler (TCD) within the past year prior to Visit 1. If this is not the case, a TCD examination must be done before proceeding in the study. 5. If =10 years old, must have had an ophthalmological examination within the past year prior to Visit 1. If this is not the case, the patient must be examined by an ophthalmologist before proceeding in the study. If local guidelines dictate ophthalmological examination at younger ages, those local guidelines should be followed. 6. If treated with hydroxyurea, the weight-adjusted dose must be stable for 3 months before screening. 7. Suitable venous access for the study-related blood sampling 8. Prior to dosing on day of randomisation (Visit 2), a negative urine (dipstick) pregnancy test performed at Screening (Visit 1) and at Visit 2 must be available for female patients of childbearing potential. 9. Females of childbearing potential (after menarche) must not become pregnant during study. Sex
Exclusion criteria
Exclusion criteria: 1. History of transient ischaemic attack (TIA) or cerebrovascular accident (ischaemic or haemorrhagic), severe head trauma, intracranial haemorrhage, intracranial neoplasm, arteriovenous malformation, aneurysm, or proliferative retinopathy. 2. Findings on TCD: Current or previous values for time averaged mean of the maximum velocity (TAMMV) that are Conditional or Abnormal. Patients with Conditional TAMMV values or higher (=153 cm/sec using TCD imaging technique [TCDi] which is corresponding to =170 cm/sec by the non-imaging technique). Both the middle cerebral artery and the internal carotid artery should be considered. Any other criteria that would locally be considered as TCD indications for chronic transfusion would also exclude the patient. 3. Active pathological bleeding or increased risk of bleeding complications according to Investigator 4. Haemoglobin 3 days per week that cannot be discontinued 8. Receiving chronic treatment with anticoagulants or antiplatelet drugs that cannot be discontinued 9. Moderate or severe hepatic impairment defined as laboratory values of alanine aminotransferase (ALT) >2 × upper limits of normal (ULN), total bilirubin >2 × ULN (unless judged by the Investigator to be caused by haemolysis), albumin 1.4, or symptoms of liver disease (eg, ascites) from test performed at Screening (Visit 1). 10. Renal failure requiring dialysis 11. Patient considered to be at risk of bradycardic events (eg, known sick sinus syndrome or second or third degree atrioventricular block) unless already treated with a permanent pacemaker. 12. Concomitant oral or intravenous therapy with strong cytochrome P450 3A (CYP3A) inhibitors, CYP3A substr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the number of VOCs which is the composite of painful crisis and/or ACS. Each component is defined as: • A painful crisis is an onset or worsening of pain that lasts at least 2 hours, for which there is no explanation other than vaso-occlusion and which requires therapy with oral or parenteral opioids, parenteral non-steroidal anti-inflammatory drugs (NSAIDs), or other analgesics prescribed by a health care provider in a medical setting (such as a hospital, clinic, or emergency room visit) or at home. An ACS is an acute illness characterized by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on a chest X-ray. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Objectives and outcome measures: 1. To compare the effect of ticagrelor vs placebo for the reduction of painful crisesOutcome measure: Number of painful crises 2. To compare the effect on ticagrelor vs placebo for the reduction of ACS Outcome measure: Number of ACSs 3. To compare the effect of ticagrelor vs placebo for the reduction of duration of painful crises Outcome measure: Duration of painful crises 4. To compare the effect of ticagrelor vs placebo on the number of VOCs requiring hospitalisation or emergency department visits. Outcome measure: Number of VOCs requiring hospitalisation or emergency department visits 5. To compare the effect of ticagrelor vs placebo on reduction of days hospitalised for VOC Outcome measure: Number of days hospitalised for VOC 6. To compare the effect of ticagrelor vs placebo on the number of acute SCD complications.Outcome measure: Number of acute SCD complications 7. To compare the effect of ticagrelor vs placebo on reduction of days hospitalised for acute SCD complications.Outcome measure: Number of acute SCD complications 8. To compare the effect of ticagrelor vs placebo on the number of sickle cell-related red blood cell (RBC) transfusions Outcome measure: Number of sickle cell-related RBC transfusions 9. To describe the health-related quality of life (HRQL) and fatigue Outcome measure: HRQL total score and by dimension using Paediatric Quality of Life Inventory (PedsQL) SCD Module and Fatigue total score and by dimension using the PedsQL Multidimensional Fatigue Scale as presented in Appendix I (age appropriate versions) 10. To describe absence from school or work due to SCD Outcome measure: Proportion of days of absence from school or work (only if going to school or work at randomisation) 11. To describe intensity of pain during VOC utcome measure: Intensity of worst pain daily during VOC -For patients =4 years of age, observer reported using the Face, Legs, Activity, Cry, Consolability | — |
Countries
United Republic of Tanzania
Contacts
Public ContactDanielle Erasmus
Snr RSU Specialist
Outcome results
None listed