A clinical trial to be conducted in many hospitals and in different countries with the medicinal substance Regadenoson to be used in a type of heart scan called 'radionuclide myocardial perfusion imaging' to see the blood flow in the heart muscle in patients aged between 1 month - 18 years.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GE Healthcare Limited

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Trial duration

9 Sep 2024 → ongoing

Decision date (initial)

2024-09-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GE HealthCare Ltd.

External identifiers

EU CT number

2024-515244-22-00

EudraCT number

2019-002615-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic

1. To evaluate the safety and tolerability of a single, body-weight adjusted intravenous (i.v.) bolus dose of regadenoson in paediatric patients aged 2 to <18 years and who weigh at least 6 kg.
2. To characterise the pharmacokinetics (PK) of a single, body-weight adjusted i.v. dose of regadenoson and the effects on heart rate (HR) in 2 paediatric populations: adolescents aged 12 to <18 years and children aged 2 to <12 years.

Secondary objectives 1

1. "1. To determine the relationship between regadenoson PK variables/exposure and changes in HR, including impact of patient factors. 2. To determine the associated myocardial hyperaemic response after administration of regadenoson using dynamic first-pass perfusion magnetic resonance imaging (MRI) and quantitative myocardial perfusion reserve (MPR) analysis."

Conditions and MedDRA coding

Patients who need to undergo a clinically indicated pharmacologic stress perfusion CMR test and who are considered fit for a pharmacological stress perfusion CMR by the investigator. The pharmacologic stress perfusion CMR may be performed in patients for further evaluation of cardiovascular conditions or diseases, such as, but not limited to, Kawasaki disease, congenital heart diseases, congenital coronary abnormalities, and post-cardiac surgery / transplantation, etc.

Study design 1 period

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000410-PIP01-08

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Male or female patient aged 2 to <18 years. 2. Patient weighs at least 6 kg. 3. Patients who need to undergo a clinically indicated pharmacologic stress perfusion CMR test and who are considered fit for a pharmacological stress perfusion CMR by the investigator. The pharmacologic stress perfusion CMR may be performed in patients for further evaluation of cardiovascular conditions or diseases such as, but not limited to, Kawasaki disease, congenital heart diseases, congenital coronary abnormalities, and post-cardiac surgery/transplantation, etc. 4. Stable medication regimen for at least 7 days prior to dosing. Stable is defined as no addition, discontinuation, or change of any medications (or their doses) that could alter the rate-pressure product (HR × BP). 5. Patients and those whose parents or legally authorised representatives are, in the investigator’s view, likely to be compliant and complete the study will be eligible to participate. 6. Post-menarcheal female patients must have a negative urine pregnancy test at screening and at pre-dose on the dosing day. 7. Post-menarcheal female patients and male patients must be practicing abstinence or be using an effective form of birth control (e.g., intrauterine device, oral contraceptives, contraceptive implants or injections, diaphragm with spermicide, cervical cap, or consort use of condom) for at least 30 days before being enrolled in the study. 8. Parents or legally authorised representatives have signed the Informed Consent Form for this study approved by the Ethics Committee or the Institutional Review Board (IRB) for the patient to participate in the study indicating that the patient (and/or a legally acceptable representative) has been informed of all pertinent aspects of the study, and, for patients who are able, have signed age-appropriate paediatric assent.

Exclusion criteria 1

1. Patients must be excluded from participating in this study if they meet any of the following criteria: 1. Prior allergic reaction to Gd contrast agents and/or regadenoson or any component of its formulation or to aminophylline or to its components (ethylenediamine and theophylline). 2. Standard clinical contraindications to MRI as per institutional guidance, including patients with cochlear implants and implanted cardiac devices, or considered unfit for a pharmacologic stress perfusion CMR test by the investigator. 3. All patients will be screened for eGFR within 24 hours before the exam, and patients presenting with eGFR <30 mL/min/1.73 m2 (by the Schwartz formula) will be excluded. 4. Pregnant or lactating females or females of childbearing potential not using an acceptable form of birth control (negative urine pregnancy test also required). 5. In the judgment of the investigator, any clinically significant ongoing medical condition (e.g., myocardial infarction, or unstable angina within 5 days, pericardial inflammatory disease, severe cardiac outflow tract obstruction, acutely decompensated heart failure, uncontrolled epilepsy, high risk for seizures, etc.) or clinically significant laboratory abnormality that is considered to potentially jeopardise the patient’s safety. 6. Patients with 2nd or 3rd degree atrioventricular block or sick sinus syndrome with or without an artificial pacemaker. 7. Known or suspected bronchoconstrictive and bronchospastic lung disease either being unstable or requiring active treatment (e.g., wheezing noted on physical exam, frequent exacerbations, or active treatment with a bronchodilator or corticosteroids). 8. Out of acceptable range sitting or semi-recumbent resting BP or HR (beats per minute [bpm]) at screening and dosing day as provided below: a) Acceptable range for BP (systolic / diastolic mmHg): 85 to 130 / 45 to 90 b) Acceptable range for HR: 55 to 100 bpm for 12 to <18 years old, and 60 to 120 bpm for 2 to <12 years old. 9. Use of any experimental or investigational drug or device within 30 days prior to dosing with study drug. 10. Consumption of methylxanthine-containing products such as caffeinated coffee, tea, caffeinated soft drinks, cocoa, or chocolate in the 48 hours prior to dosing. 11. Aminophylline or theophylline use within 24 hours, dipyridamole use within 48 hours prior to dosing. 12. History of alcohol abuse or drug addiction. 13. Positive urine drug screen at the screening visit, including amphetamines, barbiturates, cannabinoids, cocaine, ethanol and opiates, unless it is a prescribed medication containing any of these ingredients, the investigator finds it acceptable, and after agreement from the Sponsor medical monitor. 14. Currently smokes more than 5 cigarettes or equivalent per day, and if eligible for the study, would not be able to abstain from smoking from midnight prior to dosing until the end of the study period.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Primary Safety Endpoints: Occurrence of AEs, including AEs of special interest (AESIs), changes in physical examination, vital signs (BP, HR, RR, oxygen saturation, body temperature), ECG evaluation, clinical laboratory tests (serum chemistry), and post-regadenoson dosing concomitant medications. Evaluation will begin at the time of patient consent for the trial and continue through completion of the study or early withdrawal/termination. Collection of AEs will continue through study completion
2. or withdrawal/termination after the final PK blood draw (at 2 hours post-regadenoson dose) with an additional recommended observation as considered appropriate based on the patient’s condition and/or local standard of care practice and during the follow-up phone call or clinic visit at 48 hours (±12 hours).
3. Primary Pharmacokinetic Endpoints: The plasma samples for measurement of regadenoson concentrations will be collected at 1, 3, 5, 10, and 20 minutes and 1 and 2 hours post-regadenoson dose. Concentration-time profiles will be evaluated using compartmental methods and a population approach with mixed-effect modelling.
4. The effect of patient factors (such as, but not limited to, age, gender, body weight, height, body mass index [BMI], body surface area [BSA], renal function [SCr, eGFR]) on the PK variables will be assessed.

Secondary endpoints 1

1. "Secondary Pharmacodynamic Endpoints: The relationship between regadenoson PK variables/exposure and changes in HR will be assessed, including impact of patient factors (e.g., age, gender, body weight, height, BMI, BSA, renal function [SCr, eGFR])."

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GE Healthcare Limited

Sponsor organisation

GE Healthcare Limited

Address

Pollards Wood, Nightingales Lane Nightingales Lane

City

Chalfont St. Giles

Postcode

HP8 4SP

Country

United Kingdom

Scientific contact point

Organisation

GE Healthcare Limited

Contact name

David Thompson

Public contact point

Organisation

GE Healthcare Limited

Contact name

Medical Affairs

Third parties 4

Locations

3 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications