Effect of Ticagrelor vs. Placebo in the Reduction of Vaso-occlusive Crises in Pediatric Patients With Sickle Cell Disease
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Intervention: Ticagrelor; Placebo
Intervention description: The double-blinded study drug dose will be weight dependent:
≥12 to ≤24kg: Ticagrelor 15 mg, twice a day
>24 to ≤48 kg: Ticagrelor 30 mg, twice a day
>48 kg: Ticagrelor 45 mg, twice a day.; The double-blinded study drug dose will be weight dependent:
≥12 to ≤24kg: Placebo to match ticagrelor 15 mg, twice a day
>24 to ≤48 kg: Placebo to match ticagrelor 30 mg, twice a day
>48 kg: Placebo to match ticagrelor 45 mg, twice a day.
Intervention MeSH terms: Ticagrelor
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 193.0
Sex: All
Minimum age: 2 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Sickle Cell Disease; Sickle Cell Anemia; SCD; Platelet aggregation; Ticagrelor; Brilinta; VOC; Vaso-Occlusive Crises; ACS; painful crisis

Summary:

      The purpose of the study is to Evaluate the Effect of Ticagrelor versus Placebo in Reducing
      the Rate of Vaso-Occlusive Crises in Paediatric Patients with Sickle Cell Disease
    

Eligibility 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/β0 as confirmed by high-performance 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/β0 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. 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. 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 <6 g/dL from test performed at Screening (Visit 1)

          5. Platelets <100 x 10^9/L from test performed at Screening (Visit 1) Undergoing
             treatment with chronic red blood cell transfusion therapy.

          6. Undergoing treatment with chronic red blood cell transfusion therapy.

          7. Chronic use of NSAIDs defined as continuous intake >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 <35 g/L (3.5
             g/dL) and International normalised ratio (INR) >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 or moderate 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.

         13. Active untreated malaria. Patients with suspected malaria at Screening (Visit 1) will
             be tested.

         14. Known hypersensitivity or contraindication to ticagrelor

         15. 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 Screening (Visit 1)

         16. Any condition which, in the opinion of the Investigator, would make it unsafe or
             unsuitable for the patient to participate in this study

         17. Concern for the inability of the patient or caregiver (defined as legally authorized
             representative) to comply with study procedures and/or follow-up

         18. Previous randomisation in the present study.

         19. Participation in another clinical study with an IP or device during the last 30 days
             preceding screening.

         20. 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).