(21196) A multicenter, prospective, open-label study to evaluate the pharmacokinetics and safety of gadoquatrane in pediatric participants (from birth to <18 years) undergoing contrast-enhanced magnetic resonance imaging (CE-MRI)

The primary objective of this study is to evaluate the **pharmacokinetics** of gadoquatrane following a single intravenous injection of 0.04 mmol Gd/kg body weight in pediatric participants undergoing contrast-enhanced magnetic resonance imaging (CE-MRI). Understanding the pharmacokinetics is clinically relevant as it provides insights into how the drug is absorbed, distributed, metabolized, and excreted in the pediatric population, which is crucial for optimizing dosing regimens and ensuring safety.

Secondary objectives include:

• Evaluating the safety and tolerability of gadoquatrane after a single intravenous injection of 0.04 mmol Gd/kg body weight in pediatric participants undergoing CE-MRI. This is important to ensure that the contrast agent is safe for use in children and does not cause adverse effects.

The clinical trial involves a total of **69 participants** who are pediatric subjects undergoing contrast enhancement in magnetic resonance imaging (**MRI**). The study population includes both male and female participants from birth to less than 18 years of age. Participants are selected based on their clinical indication to undergo a contrast-enhanced MRI for any clinical condition in any body region, as determined by the investigator's judgment. The trial population is characterized by its inclusion of a vulnerable population, given the pediatric nature of the participants. The general health status of the participants is not specified, but they must be able to undergo study procedures. Relevant lifestyle considerations such as diet, physical activity, or habits are not detailed in the available data. Key inclusion criteria include the ability of the legal guardian(s) to provide informed consent and ensure compliance with study requirements. The trial does not specify any exclusion criteria in the provided data.

The clinical trial is designed to evaluate the **pharmacokinetics** and safety of **gadoquatrane** in pediatric participants undergoing contrast-enhanced magnetic resonance imaging (CE-MRI). This is a multicenter, prospective, open-label study involving participants from birth to less than 18 years of age. The trial aims to assess the plasma pharmacokinetics of gadoquatrane following a single intravenous injection of 0.04 mmol Gd/kg body weight. The primary endpoints include the area under the curve (AUC) of gadoquatrane, plasma clearance normalized to body weight (CL/BW), apparent volume of distribution at steady state normalized to body weight (Vss/bw), and simulation of plasma concentration at 20 minutes post-injection (C20). Secondary endpoints focus on the number and intensity of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) occurring within 24 hours post-injection or during the post-treatment period of 7 days.

The trial is expected to commence recruitment on September 29, 2023, and conclude by October 23, 2024. Participants will be involved in the study for a maximum treatment period of one day, with the study drug administered intravenously as a solution for injection. The sequence of study visits includes an initial screening visit to confirm eligibility based on inclusion criteria, followed by the administration of the study drug and subsequent monitoring for adverse events. Follow-up visits will be conducted to assess the safety and pharmacokinetic parameters of gadoquatrane. The end-of-study visit will mark the completion of the participant's involvement in the trial.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or if the investigator deems it necessary for their safety. The trial is not categorized as a low-intervention study and is classified as a Phase III trial. The study is conducted under the sponsorship of Bayer AG, with the investigational product identified as BAY 1747846. The trial does not involve a pediatric formulation, and the product is of chemical origin. The study is designed to ensure compliance with ethical standards and regulatory requirements, with informed consent obtained from the legal guardians of the participants.

The clinical trial involves the administration of **BAY 1747846**, a pharmaceutical product developed by Bayer AG. The active substance in this experimental medication is **gadoquatrane**, which is of chemical origin. The pharmaceutical form of BAY 1747846 is a **solution for injection**, specifically designed for intravenous administration. The dosage for this trial is set at 0.04 mmol of gadolinium per kilogram of body weight, administered as a single dose. The maximum treatment period is limited to one day, ensuring that the total dose does not exceed 0.04 mmol. This study aims to evaluate the pharmacokinetics and safety of gadoquatrane in pediatric participants undergoing contrast-enhanced magnetic resonance imaging (CE-MRI).

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of the experimental medication, BAY 1747846. Participant compliance with the dosing schedule is monitored to ensure accurate assessment of the pharmacokinetic profile and safety of the drug. The trial is conducted in an open-label format, allowing for direct observation of the effects of the medication without the use of blinding.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the **Area under the curve (AUC)** of gadoquatrane after a single administration, plasma clearance normalized to body weight (CL/BW) of gadoquatrane, apparent volume of distribution at steady state normalized to body weight (Vss/bw), and simulation of plasma concentration at 20 minutes post-injection (C20). These parameters will be measured to evaluate the pharmacokinetics of gadoquatrane in pediatric participants undergoing contrast-enhanced magnetic resonance imaging (CE-MRI).

Secondary endpoints focus on safety and include the number and intensity of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), occurring within 24 (±4) hours post-injection or in the post-treatment period of 7 (±1) days after the day of study intervention. The collection and analysis of these endpoints will be conducted according to the study protocol, ensuring a comprehensive evaluation of both the pharmacokinetic profile and safety of the investigational product, BAY 1747846, in the specified pediatric population.