Study to Evaluate the Effect of Ticagrelor Versus Placebo in Reducing Vaso-Occlusive Crises Rate in Pediatric Patients With Sickle Cell Disease. — HESTIA5  

Sickle Cell Disease Clinical Trial

Official title: A Randomised, Double Blind, Parallel Group, Multicentre, Phase III Study to Evaluate the Effect of Ticagrelor Versus Placebo in Reducing the Number of Vaso-Occlusive Crises in Paediatric Patients Aged 6 Months to <18 Years With Sickle Cell Disease (HESTIA5)

Status Withdrawn

Clinical Trial 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

Clinical Trial Description

• HESTIA5 will evaluate the efficacy, safety and tolerability of ticagrelor versus placebo in children with SICKLE CELL DISEASE during treatment for at least 12 months and up to a maximum of 24 months.

• The target population are children (males and females) aged 6 months to <18 years and body weight ≥6 kg diagnosed with homozygous sickle cell or sickle beta-zero-thalassaemia confirmed by high-performance liquid chromatography or hemoglobin electrophoresis. The aim is to randomise 20 patients in the age group 6 to <24 months. At least 50 patients should be randomised in each of the age groups: ≥2 to <12 years and ≥12 to <18 years.

• Prior to randomisation in this study, patients aged 6 to <24 months will undergo a 14-day Run in period in which they will receive open-label ticagrelor twice a day for 14 days according to weight. Run-in period includes 4 visits, called R1, R2, R3 and R4. The run-In period is to ensure that the treatment is well-tolerated, and that the exposure is in line with model-based predictions following repeated twice a day dosing with ticagrelor in this age group. At the end of the Run-in period (Visit R4), the patient will take his/her final dose of open-label IP and await the independent Data Monitoring Committee chairman's evaluation of tolerability, safety and exposure before being eligible to enter the Screening period for randomisation. Patients who complete the Run-in period according to the protocol must also meet all the inclusion/exclusion criteria detailed in Protocol, to proceed to randomisation.

• To be eligible for the study, patients must have experienced at least 2 VASO-OCCLUSIVE CRISES (defined as painful crisis and/or ACUTE CHEST SYNDROME) events in the past 12 months prior to Visit 1, (patients aged 2 to <18 years) and prior to visit R1 (patients aged 6 to <24 months) indicating that the severity of the patient's disease justifies preventive chronic long-term treatment. Even if painful VASO-OCCLUSIVE CRISES are uncommon in infants and become more frequent in older children, data show that symptoms like dactylitis precede more severe events and confirm that children who have early dactylitis are more likely to have severe events later in life.

• Study participants should receive standard of care for SICKLE CELL DISEASE, adjusted to the individual patient at the discretion of the investigator, including routine health care screening examinations and immunizations to local guidelines and health care programmes. Study drug will be given on the background of standard treatments for SICKLE CELL DISEASE. Study participants are not withheld from any other treatments that may be used in SICKLE CELL DISEASE (eg., hydroxyurea) during the trial, which is important considering the use of a placebo control group. However, restrictions apply to some medications and interventions that may be necessary for the patient's health and well-being during the study.

• Patients are to be followed until a common study end date (CSED) is reached defined as 12 months after the last patient is randomized. Treatment duration is at least 12 months for study participants, and patients will continue on treatment until 12 months after last randomized patient or up to a maximum of 24 months. The expected average follow-up is 18 months, assuming a uniformly distributed enrolment period of 12 months. Considering inclusion of patients with at least 2 VASO-OCCLUSIVE CRISES in the past year, this treatment duration is considered long enough to evaluate effects on VASO-OCCLUSIVE CRISES events as well as to capture safety and tolerability data supporting a potential future long term use of ticagrelor.

• Due to ticagrelor mechanism of action and the potential to reduce symptoms caused by ischemia during a vaso-occlusion, a composite endpoint with painful crises and/or ACUTE CHEST SYNDROME has been selected for the primary endpoint. Painful crisis is the most common reason for emergency department visits for patients with SICKLE CELL DISEASE with a significant impact on young patients' lives, affecting them physically and emotionally. Secondary endpoints are included to broaden the understanding of effects in patients with SICKLE CELL DISEASE and to also assess potential benefits on symptomatic disease burden and health-related quality of life (HRQL).

• Patients will be treated with 5, 10, 15, 30 and 45 mg twice a day or matching placebo, depending on body weight. ;

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

• NCT number: NCT04293172
• Study type: Interventional
• Source: AstraZeneca
• Status: Withdrawn
• Phase: Phase 3
• Start date: June 30, 2020
• Completion date: October 10, 2022