Children, Contrast Enhancement in Magnetic Resonance Imaging
Conditions
Brief summary
Researchers are looking for a better way to help children under the age of 18 with any known or suspected problems scheduled for a "contrast-enhanced" Magnetic Resonance Imaging (MRI). MRI is used by doctors to create detailed images of the inside of the body to identify health problems. Sometimes doctors need to inject a contrast agent into a patient's vein to perform a "contrast-enhanced" MRI (CE-MRI). Such CE-MRI examinations may support doctors to identify certain health problems or improve their evaluation. The contrast agents commonly used in MRI are gadolinium-based contrast agents (GBCAs). GBCAs contain a "rare earth" element called gadolinium (Gd), which is needed for the increase in signal intensity and contrast in MRI. The gadolinium in these contrast agents is caged in a molecule (chelate complex). Researchers are developing new contrast agents with a lower amount of Gd needed per CE-MRI investigation. Gadoquatrane is one of these new contrast agents. It has been tested in several studies previously. The main purpose of this study is to learn how gadoquatrane moves into, through, and out of the body and how safe it is in children. The researchers will measure the amount of gadoquatrane in the blood at different time points after a single injection. The participants will undergo an MRI examination and receive gadoquatrane once at a dose of 0.04 mmol Gd/kg (corresponding to 0.1 mL/kg). It is injected into the participant's vein (also called an intravenous injection) during the MRI examination. Each participant will be in the study for between 8 and 38 days with up to 5 doctor visits, including the screening phase of up to 28 days with no more than 2 visits. Once a participant has received the injection of gadoquatrane, the remaining study duration is 7 (±1) days. At the start or during the study, the doctors and their study team will: * check the weight and height of the participant, * ask for information including age and medical history, * take participants' blood samples, * ask participants and/or their guardians questions about medicines they are taking, * check blood pressure, heart rate and body temperature, * check the area where the participants had the intravenous injection, * do pregnancy tests in girls of childbearing age, * review the MRI scans obtained in the study and decide on the diagnosis * ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatments.
Interventions
0.04 mmol Gd/kg body weight, solution for intravenous injection, single dose
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Participants from birth to \<18 years of age at the time of signing the informed consent form. * Participants who have a clinical indication to undergo a CE-MRI for any clinical condition in any body region and who can undergo study procedures as per Investigator judgement. * Participants can be male or female (according to their reproductive organs and functions assigned by chromosomal complement). * Female contraception and barriers as well as pregnancy testing is required as appropriate for the age and sexual activity of pediatric participants and as required by local regulations. * The legal guardian(s) is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. * When applicable by law for a participant, a legal guardian must be available to help the study-site personnel ensure follow up, accompany the participant to the study site on each assessment day, and consistently and consecutively be available to provide information on the participant during the scheduled study visits.
Exclusion criteria
* Body weight \<2500 g at screening and baseline * The medical condition and/or local allowance for maximum blood draw in the pediatric participant is not suitable for study procedures, including pharmacokinetics (PK) and safety blood draws, without compromising any expected clinical care/procedure need. * Acute kidney injury (i.e., acute renal failure). * Age-adjusted renal function is "decreased" (eGFR \<80% of age adjusted normal renal function) as evaluated by the investigator based on a serum or plasma creatinine result obtained within 2 weeks prior to study intervention. * Considered clinically unstable or has a concurrent/concomitant condition that may not allow participation for the full planned study period, in the judgement of the investigator. * History of moderate to severe allergic-like reaction to any GBCA. * Bronchial asthma considered unstable or had major therapeutical modification within last 4 weeks. * Severe cardiovascular disease, except for cardiac or vascular magnetic resonance (MR), if considered clinically justified by the investigator. * Planned or expected intervention (e.g., treatment or procedure) or change in treatment (e.g. start of chemotherapy) that may significantly affect study parameters (i.e. safety/adverse events \[AEs\] \[e.g. confounding AEs or safety events due to surgery or chemotherapy\], PK parameters) or would prevent the participant from performing study procedures, from the administration of gadoquatrane up to the 24 h ± 4 h follow-up. * Participants who received or will receive any other contrast agent within 72 hours prior to gadoquatrane injection or up to 72 hours after gadoquatrane injection. * Contraindications to the administration of GBCAs (depending on local product label), or history of adverse reaction to GBCAs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) of Gadoquatrane After Single Administration | Up to 8 hours post injection | Median values (5th and 95th percentile) |
| Plasma Clearance Normalized to Body Weight (CL/BW) of Gadoquatrane After Single Administration | Up to 8 hours post injection | Median values (5th and 95th percentile) |
| Apparent Volume of Distribution at Steady State Normalized to Body Weight (Vss/BW) of Gadoquatrane After Single Administration | Up to 8 hours post injection | Median values (5th and 95th percentile) |
| Simulation of Plasma Concentration at 10, 20 and 30 Minutes Post-injection (C10, C20 and C30) | At 10, 20 and 30 minutes post injection | Median values (5th and 95th percentile) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events, Including Serious Adverse Events | Within 24 (± 4) hours post injection | Number of participants with treatment emergent adverse events (TEAEs) including serious adverse events (SAEs). An AE is considered treatment-emergent, if it started or worsened within 24 (±4) hours post-injection of gadoquatrane. |
| Number of Participants With Treatment Emergent Adverse Events Per Intensity | Within 24 (± 4) hours post injection | Number of participants with TEAEs per severity. An AE is considered treatment-emergent, if it started or worsened within 24 (±4) hours post-injection of gadoquatrane. |
| Number of Participants With Post-treatment Adverse Events, Including Serious Adverse Events | Between 24 (± 4) hours and 7 (± 1) days after the day of study intervention | Number of participants with post-treatment adverse events (PTAEs). An AE is considered a PTAE if it started or worsened between the 24 ± 4 hours after gadoquatrane administration and the follow-up period of 7 ± 1 day post-injection. |
| Number of Participants With Post-treatment Adverse Events Per Intensity | Between 24 (± 4) hours to 7 (± 1) days after the day of study intervention | Number of participants with PTAEs. An AE is considered a PTAE if it started or worsened between the 24 ± 4 hours after gadoquatrane administration and the follow-up period of 7 ± 1 day post-injection. |
Countries
Argentina, Bulgaria, Canada, China, Czechia, Germany, Japan, Poland, Sweden, United States
Participant flow
Recruitment details
A total of 105 participants signed the ICF. 8 participants were screen failures, 3 withdrew their consent and 1 participant could not continue due to internal site issues. Of the 105 participants, 93 received the study drug. 92 completed the overall study. 1 participant did not finish the FUP visit. The study was conducted in 29 sites in 10 countries from 16 August 2023 (First Patient First Visit) to 25 September 2024 (Last Patient Last Visit).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous Total | 7.13 Years STANDARD_DEVIATION 5.48 |
| Body Weight (Bw) | 29.98 Kg STANDARD_DEVIATION 23.65 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 74 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 35 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 53 Participants |
| Sex: Female, Male Female | 38 Participants |
| Sex: Female, Male Male | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 93 |
| other Total, other adverse events | 20 / 93 |
| serious Total, serious adverse events | 3 / 93 |
Outcome results
None listed