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

NCT04293172 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: D5136C00013
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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

Conditions

Sickle Cell Disease

Keywords

Ticagrelor; Vaso-Occlusive Crises; Paediatric Patients; 6 Months to <18 Years; Sickle Cell Disease; Sickle Cell Anemia; Platelet aggregation; Brillinta; Acute Chest Syndrome; painful crisis

Outcome Measures

Primary Outcomes (1)

• Number of Vaso-Occlusive Crises

  Vaso-occlusive crises (VOC) defined as the composite of a painful crisis and/or an Acute Chest Syndrome (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 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.

  Up to end of study visit (12 to 24 months)

Secondary Outcomes (16)

• Number of Vaso-Occlusive Crises in patients aged 2 to <18 years

  Up to end of study visit (12 to 24 months)

• Number of painful crises

  Up to end of study visit (12 to 24 months)

• Number of Acute Chest Syndromes

  Up to end of study visit (12 to 24 months)

• Duration of painful crises

  Up to end of study visit (12 to 24 months)

• Number of Vaso-Occlusive Crises requiring hospitalisation or emergency department visits

  Up to end of study visit (12 to 24 months)

Study Arms (2)

Ticagrelor

EXPERIMENTAL

The double-blinded study drug dose will be weight dependent.

Drug: Brilinta

Placebo

PLACEBO COMPARATOR

The double-blinded study drug dose will be weight dependent

Drug: Placebo

Interventions

Brilinta DRUG

Patients in the open-label Run-in period (patients aged 6 to \<24 months only) will receive ticagrelor 5 mg twice a day (body weight 6 to ≤9 kg), 10 mg twice a day (body weight \>9 to ≤12 kg) or 15 mg twice a day (body weight \>12 to ≤24 kg) for 14 days. The double-blind IP will be based on 5 weight bands: * 6 to ≤9 kg: ticagrelor 5 mg or matching placebo, twice a day * \>9 to ≤12 kg: ticagrelor 10 mg or matching placebo, twice a day * \>12 to ≤24 kg: ticagrelor 15 mg or matching placebo, twice a day * \>24 to ≤48 kg: ticagrelor 30 mg or matching placebo, twice a day * \>48 kg: ticagrelor 45 mg or matching placebo, twice a day

Ticagrelor

Placebo DRUG

Patients in the open-label Run-in period (patients aged 6 to \<24 months only) will receive ticagrelor 5 mg twice a day (body weight 6 to ≤9 kg), 10 mg twice a day (body weight \>9 to ≤12 kg) or 15 mg twice a day (body weight \>12 to ≤24 kg) for 14 days. The double-blind IP will be based on 5 weight bands: * 6 to ≤9 kg: ticagrelor 5 mg or matching placebo, twice a day * \>9 to ≤12 kg: ticagrelor 10 mg or matching placebo, twice a day * \>12 to ≤24 kg: ticagrelor 15 mg or matching placebo, twice a day * \>24 to ≤48 kg: ticagrelor 30 mg or matching placebo, twice a day * \>48 kg: ticagrelor 45 mg or matching placebo, twice a day

Placebo

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).
• 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.
• 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.
• 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.
• 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.
• If treated with hydroxyurea or L-glutamine, the weight-adjusted dose must be stable for 3 months before screening.
• Suitable venous access for the study-related blood sampling.
• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• 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.
• Pathological finding on any other imaging assay indicating increased risk for intracerebral bleeding or thromboembolism.
• International normalised ratio (INR) \>1.4 or active pathological bleeding or increased risk of bleeding complications according to Investigator.
• 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).
• 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).
• Undergoing treatment with chronic red blood cell transfusion therapy.
• Chronic use of NSAIDs defined as continuous intake \>3 days per week that cannot be discontinued.
• Receiving chronic treatment with anticoagulants or antiplatelet drugs that cannot be discontinued.
• 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).
• Renal failure requiring dialysis.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Iqvia Pty Ltd: collaborator

MeSH Terms

Conditions

Anemia, Sickle Cell; Vaso-Occlusive Crises; Acute Chest Syndrome

Interventions

Ticagrelor

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Anders Berggren, MD, PhD

  AstraZeneca

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2020
• First Posted: March 3, 2020
• Study Start: June 30, 2020
• Primary Completion: October 10, 2022
• Study Completion: October 10, 2022
• Last Updated: July 15, 2020

Record last verified: 2020-07