A clinical study to evaluate the safety and effect of the study drug (Ticagrelor) vs placebo ("dummy drug") in children, aged 2 to less than 18 years with Sickle Cell Disease

• Register: EUCTR
• Last refreshed on: 4 January 2022
• Main ID: EUCTR2017-002421-38-BE
• Date of registration: 12/04/2018
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A clinical study to evaluate the safety and effect of the study drug (Ticagrelor) vs placebo ("dummy drug") in children, aged 2 to less than 18 years with Sickle Cell Disease
• Scientific title: A Randomised, Double-Blind, Parallel-Group, Multicentre, Phase III Study to Evaluate the Effect of Ticagrelor versus Placebo in Reducing the Rate of Vaso-Occlusive Crises in Paediatric Patients with Sickle Cell Disease (HESTIA3) - HESTIA3
• Date of first enrolment: 02/07/2018
• Target sample size: 182
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002421-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Brazil, Canada, Egypt, Ghana, Greece, India, Italy, Kenya, Lebanon, Saudi Arabia, South Africa, Spain, Tanzania, United Republic of, Turkey, Uganda, United Kingdom, United States

Contacts

• Name: Information Centre
• Affiliation: AstraZeneca AB

• Name: Information Centre
• Affiliation: AstraZeneca AB

Key inclusion & exclusion criteria

Inclusion criteria:
1. 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 high-performance liquid chromatography or haemoglobin electrophoresis.
2. 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.
3. 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.
4. 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 182
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 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)
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 (TB) >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 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 authorised 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 enrolment.
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).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Sickle Cell Disease
MedDRA version: 20.0 Level: LLT Classification code 10040644 Term: Sickle cell disease System Organ Class: 100000004850

Intervention(s)

Product Name: Ticagrelor
Pharmaceutical Form: Tablet
INN or Proposed INN: Ticagrelor
CAS Number: 274693-27-5
Current Sponsor code: AZD6140
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Number of VOCs

Timepoint(s) of evaluation of this end point: Up to End of Study Visit {12 to 24 months}

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: - compare the effect of ticagrelor vs placebo for reduction of; painful crises, ACS, duration of painful crises, days hospitalised for VOC, days hospitalised for acute SCD complications
- compare the effect of ticagrelor vs placebo on the number of VOCs requiring hospitalisation or emergency department visits
- compare the effect of ticagrelor vs placebo on the number of acute SCD complications
- compare the effect of ticagrelor vs placebo on the number of sickle cell-related red blood cell (RBC) transfusions
- describe the health-related quality of life (HRQL) and fatigue
- describe intensity of pain during VOC

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - Secondary end points will be measured up to Safety Follow up Visit (End of Study + 14 days)
- HRQL (PedsQL) assessment will be performed at visits on day 0, 6mo, 12mo, 18mo, EOS (12-24 months)

Secondary end point(s): - Number of painful crises
- Number of ACSs
- Duration of painful crises
- Number of VOCs requiring hospitalisation or emergency department visits
- Number of days hospitalised for VOC
- Number of acute SCD complications
- Number of days hospitalised for acute SCD complications
- Number of sickle cell-related RBC transfusions
- 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
- Intensity of worst pain daily during VOC

Secondary ID(s)

NCT03615924

D5136C00009

2017-002421-38-GB

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date: 02/07/2018
Contact:

Results

• Results available: Yes
• Date Posted: 22/02/2021
• Date Completed: 13/08/2020
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-002421-38/results