Phase 4 Paediatric Study to Evaluate Sonazoid™ Safety and Efficacy for Contrast-Enhanced Ultrasound Liver Imaging.

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]

Decision date (initial)

2025-07-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GE HealthCare Ltd and its Affiliates

External identifiers

EU CT number

2023-505569-95-00

ClinicalTrials.gov

NCT06639828

ISRCTN

ISRCTN17927667

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Safety, Efficacy

To evaluate the diagnostic accuracy of ultrasound images enhanced with Sonazoid™ (perflubutane microbubbles) for differentiating benign vs malignant focal liver lesions (FLL) in paediatric patients during vascular phase imaging.

Secondary objectives 6

1. To assess the safety profile of intravenous administration of Sonazoid™ in the paediatric population.
2. To compare the diagnostic accuracy of Sonazoid™-enhanced ultrasound images vs unenhanced ultrasound images for differentiating benign from malignant FLL in paediatric patients during vascular phase imaging.
3. To compare the diagnostic accuracy of Sonazoid™-enhanced ultrasound images vs unenhanced ultrasound images for differentiating benign from malignant FLL in paediatric patients during vascular and Kupffer phases imaging.
4. To assess whether the use of Sonazoid™-enhanced ultrasound images vs unenhanced ultrasound images affects the reader’s confidence in their diagnosis of benign vs malignant FLL in paediatric patients during vascular phase imaging.
5. Exploratory Objective: To assess whether the use of Sonazoid™-enhanced ultrasound images vs unenhanced ultrasound images affects the reader’s confidence in their diagnosis of benign vs malignant FLL in paediatric patients during both vascular phase imaging and Kupffer phase imaging.
6. Exploratory Objective: To describe the CEUS specific FLL diagnosis observed in paediatric patients during both vascular phase imaging and combined vascular and Kupffer phase imaging.

Conditions and MedDRA coding

Focal Liver Lesion

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003037-PIP02-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. The subject is <18 years of age on the day of consent.
2. The subject has at least 1 untreated FLL with ≤8 lesions (excluding cysts), with ≤8 cm confirmed in a diagnostic examination performed in the past month (or past 3 months if the lesion was benign) and that could also be visualised when obtained via unenhanced ultrasound imaging.
3. The subject has had a dynamic CECT or CEMRI examination within the past month for malignant lesions, or 3 months for benign lesions if performed retrospectively, or is scheduled to have one in the month following inclusion in the study, and these images are/would be available.
4. The subject can comply with study procedures.
5. Parents or legally authorised representatives have signed the Informed Consent Form approved for this study by the Independent Review Board (IRB)/Independent Ethics Committee (IEC). The form will indicate that the patient (and/or a legally acceptable representative) has been informed of all pertinent aspects of the study. Patients who are able to provide assent have signed an age-appropriate paediatric assent form
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 who are sexually active with a partner of childbearing potential must be practicing abstinence or be using an effective form of birth control (See Section 8.6) for ≥30 days before being enrolled in the study.
8. The subject has a body weight of 3 kg or greater.
9. The subject has a negative egg allergy test if the egg allergy status of the subject is unknown.

Exclusion criteria 9

1. The subject has a known or suspected hypersensitivity to any of the components of Sonazoid™, including a history of allergies to eggs or egg products (i.e., manifested by full body rash, respiratory difficulty, oral or laryngeal swelling, hypotension, or shock), or a positive result from an egg-allergy test performed at screening. Note: If the egg-allergy status is unknown, an egg-allergy test must be performed at screening and the result must be negative.
2. The subject has an acute clinically fatal condition (i.e., the expected survival is ≤6 months).
3. The subject has previously received Sonazoid™ or another ultrasound contrast agent within the past 30 days.
4. The subject had undergone or is planning to undergo an examination with a contrast agent (i.e., iodinated x-ray contrast agent, MRI contrast agent or another ultrasound contrast agent) within the 24 hours before or after Sonazoid™ injection.
5. The subject has undergone or was undergoing systemic or loco-regional chemotherapy or radiation therapy.
6. The subject is participating in another clinical trial with an unregistered medicinal product, or less than 30 days has passed since the subject completed participation in such a trial.
7. The subject is a pregnant or lactating female.
8. The physician judges that a large-enough needle (24-gauge or larger) cannot be inserted.
9. The subject has a known right-left cardiac shunt.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The accuracy, sensitivity and specificity of the diagnosis based on the independent blinded read of the Sonazoid™-enhanced imaging for lesion differentiation (benign or malignant FLLs) during vascular phase imaging. The WFUMB-EFSUMB guidelines for interpreting CEUS of the liver in adults shall be used for interpreting the images and the subject’s baseline diagnosis (well-established by CECT, CEMRI or biopsy) will be used as the reference diagnosis/standard of truth.

Secondary endpoints 8

1. Accuracy, sensitivity and specificity of the diagnosis (benign or malignant FLL) based on the Sonazoid™-enhanced imaging by vascular phase imaging, as compared with the unenhanced ultrasound imaging, when the baseline diagnosis is used as the reference standard.
2. Accuracy, sensitivity and specificity of the diagnosis (benign or malignant FLL) based on the Sonazoid™-enhanced imaging by vascular phase and Kupffer phase imaging, as compared with the unenhanced ultrasound imaging, when the baseline diagnosis is used as the reference standard.
3. The difference in the diagnostic confidence score for the unenhanced ultrasound imaging and that for the Sonazoid™-enhanced ultrasound imaging based on the vascular phase.
4. Exploratory outcome measure: The difference in the diagnostic confidence score for the unenhanced ultrasound imaging and that for the Sonazoid™-enhanced ultrasound imaging based on the vascular and Kupffer phase.
5. Exploratory outcome measure: CEUS specific FLL diagnosis throughout the vascular phase of imaging and the vascular and Kupffer phases of imaging according to WFUMB-EFSUMB guidelines (HCC, metastasis, haemangioma, FNH, focal fatty infiltration, focal fatty sparing) observed in paediatric patients.
6. Safety outcome measure: Treatment-emergent AEs (TEAEs) defined as AEs that occurred at any timepoint from the administration of Sonazoid™ to the end of the study (72 hours after Sonazoid™ administration), including drug-related TEAEs
7. Safety outcome measure: Serious AEs (SAEs)
8. Safety outcome measure: Physical examination, vital signs, blood and urine samples for clinical laboratory testing and injection site monitoring

Investigational products

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

Test 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

GE Healthcare

Third parties 2

Locations

2 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Results and documents

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

Documents 29 files

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

Application history

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