Study to Evaluate the Effect of Ticagrelor Versus Placebo in Reducing Vaso-Occlusive Crises Rate in Pediatric Patients With Sickle Cell Disease.

• Status: Withdrawn
• Trial end date: 2022-10-10
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to compare the effect of ticagrelor vs placebo for the reduction of Vaso-Occlusive crises in paediatric patients with Sickle Cell Disease

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca
• Collaborator: Iqvia Pty Ltd
• Treatments: Ticagrelor

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. Children aged 6 months to <18 years of age and body weight ≥6 kg diagnosed with HbSS or HbS/β0 as confirmed by high-performance liquid chromatography (HPLC) or haemoglobin electrophoresis.

3. Have experienced at least 2 VASO-OCCLUSIVE CRISES (painful crisis and/or ACUTE CHEST SYNDROME) as judged by the Investigator in the past 12 months prior to Visit R1 (patients aged 6 to <24 months) or Visit 1 (patients aged 2 to <18 years). These VASO-OCCLUSIVE CRISES need to be documented in the patient's medical records or in other documents that can be reconciled.

4. If aged 2 to ≤16 years, must have had a TCD within the past year prior to Visit 2. If this is not the case, a TCD examination must be done before randomisation.

5. If aged ≥10 years, 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 or L-glutamine, 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 Enrolment (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 the study. Sexually active females must use a highly effective method of contraception which results in a low failure rate (ie, less than 1% per year). If use of effective contraception cannot be secured in sexually active females, the patient cannot be included in this study.

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 <6 g/dL 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).

7. Platelets <100 × 109/L 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).

8. Undergoing treatment with chronic red blood cell transfusion therapy.

9. Chronic use of NSAIDs defined as continuous intake >3 days per week that cannot be discontinued.

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 <35 g/L (3.5 g/dL) and INR >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, 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 last 30 days preceding screening.

21. Involvement of member of patient's family, or patient self, in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).