Sickle Cell Disease MedDRA version: 21.0 Level: LLT Classification code 10040645 Term: Sickle cell disease NOS System Organ Class: 100000004850
Conditions
Sponsors
AstraZeneca AB
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). The Informed consent form (ICF) process is described in Appendix A 3 of the protocol. 2 Children aged 6 months to =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1 As judged by the Investigator, any evidence of unsuitability which in the Investigator’s opinion makes it undesirable for the patient to participate in the study. 2 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. 3 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. 4 Pathological finding on any other imaging assay indicating increased risk for intracerebral bleeding or thromboembolism. 5 International normalised ratio (INR) >1.4 or active pathological bleeding or increased risk of bleeding complications according to Investigator. 6 Haemoglobin 3 days per week that cannot be discontinued (see Appendix K of the protocol). 10 Receiving chronic treatment with anticoagulants or antiplatelet drugs that cannot be discontinued. 11 Moderate or severe hepatic impairment defined as laboratory values of alanine aminotransferase (ALT) >2×upper limit 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 Visit R1 and Visit 1 (patients aged 6 to <24 months) or at Enrolment (Visit 1) (patients aged 2 to <18 years). 12 Renal failure requiring dialysis. 13 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. 14 Concomitant oral or intravenous therapy with strong cytochrome P450 3A (CYP3A) inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers (see full list in Appendix K of the protocol), which cannot be stopped at least 5 half-lives before randomisation. 15 Active untreated malaria. Patients with suspected malaria at Visit R1 (patients aged 6 to <24 months) or at Enrolment (Visit 1) (patients aged 2 to <18 years) will be tested. 16 Known hypersensitivity or contraindication to ticagrelor. 17 Patients who are currently pregnant or breastfeeding or planning to become pregnant during the study or have given birth less than 3 months prior to Enrolment (Visit 1). 18 Concern for the inability of the patient or caregiver (defined as legally authorised representative) to comply with study procedures and/or follow-up. 19 Previous randomisation in the present study or participation in any previous HESTIA study. 20 Participation in another clinical study with an IP or device during the l
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the effect of ticagrelor vs placebo for the reduction of VOCs, which is the composite of painful crisis and/or ACS, in paediatric patients with SCD;Secondary Objective: Key secondary objectives are:To compare the effect of ticagrelor vs placebo for the reduction of VOCs, which is the composite of painful crisis and/or ACS, in paediatric patients with SCD aged 2 to <18 years To compare the effect of ticagrelor vs placebo for the reduction of painful crises To compare the effect on ticagrelor vs placebo for the reduction of ACS To compare the effect of ticagrelor vs placebo for the reduction of duration of painful crises To compare the effect of ticagrelor vs placebo on the number of VOCs requiring hospitalisation or emergency department visits To compare the effect of ticagrelor vs placebo on reduction of days hospitalised for VOC To compare the effect of ticagrelor vs placebo on the number of acute SCD complications To compare the effect of ticagrelor vs placebo on reduction of days hospitalised for acute SCD complications To compare the effect of ticagrelor vs placebo on the number of sickle cell-related red blood cell (RBC) transfusions;Primary end point(s): Number of Vaso-occlusive crisis (VOCs);Timepoint(s) of evaluation of this end point: Up to End of Study Visit (12 to 24 months) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Number of VOCs in patients aged 2 to <18 years 2.Number of painful crises 3.Number of ACSs 4.Duration of painful crises 5.Number of VOCs requiring hospitalisation or emergency department visits 6.Number of days hospitalised for VOC 7.Number of acute SCD complications 8.Number of days hospitalised for acute SCD complications 9.Number of sickle cell-related RBC transfusions 10.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 (age appropriate versions: 2 to 4 years; 5 to 7 years; 8 to 12 years; 13 to 18 years); HRQL total score and by dimension using the PedsQL Infant Scale (age appropriate versions: 1 to 12 months; 13 to 24 months) 11.Proportion of days of absence from school or work (only if going to school or work at randomisation) 12.Intensity of worst pain daily during VOC •For patients aged =4 years, observer reported using the Face, Legs, Activity, Cry, Consolability (FLACC) scale 13.Type of analgesics (opioid and non-opioid) use 14. •For patients aged =4 years taking the tablet dispersed or whole, an observer assessment of palatability and swallowability will be undertaken •For patients aged =5 years taking the tablet dispersed or whole, palatability will be assessed and categorised using the Facial Hedonic Scale;Timepoint(s) of evaluation of this end point: 1,2,3,4,5,6,7,8, 9,11, 12,13 - Secondary end points will be measured up to End of Study Visit 10-HRQL (PedsQL) assessment will be performed at randomization visit, visits 9, 15, 21 and End of Study 14-Palatability/swallowability will be performed at randomization visit and visits 2 and 9 | — |
Countries
Egypt, Ghana, India, Italy, Kenya, Lebanon, Nigeria, Oman, Tanzania, United Republic of, Turkey, Uganda, United Kingdom, United States
Contacts
Public ContactInformation Centre
AstraZeneca AB
Outcome results
None listed