A Phase 1, Multicentre, Open-Label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a Single IV Dose of Rezafungin Acetate in Paediatric Subjects from Birth to <18 Years of Age, Receiving Systemic Antifungals as Prophylaxis for Invasive Fungal Infection or to Treat a Suspected or Confirmed Fungal Infection

The primary objective of this study is to evaluate the **pharmacokinetics** of a single intravenous (IV) dose of rezafungin in pediatric subjects from birth to less than 18 years of age. These subjects are receiving concomitant systemic antifungals either as prophylaxis for invasive fungal infection (IFI) or to treat a suspected or confirmed fungal infection. Understanding the pharmacokinetics in this population is clinically relevant as it informs dosing strategies and ensures effective and safe use of rezafungin in pediatric patients, who may have different metabolic rates and drug clearance compared to adults.

The secondary objective is to assess the safety and tolerability of a single IV dose of rezafungin in the same pediatric population. This evaluation is crucial to ensure that the treatment is not only effective but also safe for use in children, who may have different adverse reaction profiles compared to adults. The study aims to provide comprehensive data on the safety profile of rezafungin when used alongside other systemic antifungals in this vulnerable population.

The clinical trial involves a total of **16 participants** who are pediatric subjects ranging from birth to less than 18 years of age. The study population includes both male and female subjects who are receiving concomitant systemic antifungals, either orally or intravenously, as prophylaxis for invasive **fungal infections** or to treat a suspected or confirmed fungal infection. Participants were selected based on their current antifungal treatment regimen, and the trial includes a vulnerable population due to the age range of the subjects. The health status of the participants is characterized by their need for antifungal prophylaxis or treatment, indicating a susceptibility to or presence of fungal infections. Lifestyle considerations such as diet and physical activity are not specified, as the primary focus is on the pharmacokinetics of the investigational drug in this specific pediatric population.

The clinical trial is a **Phase 1**, multicentre, open-label study designed to evaluate the pharmacokinetics, safety, and tolerability of a single intravenous dose of **rezafungin acetate** in paediatric subjects from birth to less than 18 years of age. The trial targets individuals receiving systemic antifungals as prophylaxis for invasive **fungal infections** or to treat a suspected or confirmed fungal infection. The study is expected to commence recruitment on July 24, 2023, and conclude by February 25, 2027. Participants will be involved in the study for a duration that includes an initial screening visit, followed by the administration of the investigational product, and subsequent follow-up visits to monitor pharmacokinetic parameters and safety outcomes.

The trial will assess primary endpoints such as Cmax, Tmax, AUC0-t, AUC0-∞, CL, Vss, Vz, and t1/2, with secondary endpoints focusing on the incidence of treatment-emergent adverse events, clinical laboratory evaluations, vital signs, 12-lead electrocardiograms, and physical examination findings. The inclusion criteria specify that eligible participants are male or female paediatric subjects from birth to less than 18 years of age who are receiving concomitant systemic antifungals. The study does not list specific exclusion criteria. Participants may be withdrawn from the study if they experience significant adverse events or if they do not comply with the study protocol.

The sequence of study visits includes an initial screening visit to determine eligibility, followed by the administration of the investigational product. Subsequent follow-up visits will be scheduled to collect pharmacokinetic data and monitor safety parameters. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any adverse events are addressed. The study is not categorized as low intervention, and it is not a randomized or double-blind trial, given its open-label design. The investigational product, REZZAYO 200 mg powder for concentrate for solution for infusion, is administered via intravenous infusion, and the study is sponsored by Mundipharma Research Ltd.

The clinical trial involves the administration of **REZAFUNGIN ACETATE**, marketed under the name **REZZAYO 200 mg powder for concentrate for solution for infusion**. This investigational medicinal product is formulated as a **powder for concentrate for solution for infusion**. The active substance, rezafungin acetate, is classified as a protein of other origin. The pharmaceutical form is specifically designed for intravenous infusion, ensuring direct delivery into the bloodstream. The trial protocol specifies a single intravenous dose to be administered to pediatric subjects ranging from birth to less than 18 years of age. The primary objective is to evaluate the pharmacokinetics, safety, and tolerability of this single dose in subjects receiving systemic antifungals as prophylaxis for invasive fungal infection or for the treatment of a suspected or confirmed fungal infection. The product is not a pediatric formulation, and it holds an orphan drug designation under the number EU/3/20/2385.

In addition to the experimental treatment, participants may receive concomitant systemic antifungals as part of the standard-of-care therapy. These non-experimental treatments are administered to provide prophylaxis against invasive fungal infections or to treat existing fungal infections. The study does not include a placebo or comparator treatment, focusing solely on the pharmacokinetic profile of rezafungin acetate. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol and to accurately assess the pharmacokinetic parameters of the investigational drug.

Efficacy in this clinical trial will be assessed through the evaluation of pharmacokinetic (PK) parameters of a single intravenous dose of **rezafungin acetate** in pediatric subjects. The primary endpoints include the assessment of PK parameters such as maximum concentration (Cmax), time to reach maximum concentration (Tmax), area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t), area under the concentration-time curve from time zero to infinity (AUC0-∞), clearance (CL), steady-state volume of distribution (Vss), volume of distribution during the terminal phase (Vz), and half-life (t1/2). Additionally, rezafungin plasma concentrations will be measured in Part 3 of the study.

The secondary endpoints focus on safety evaluations, which will be based on the clinical review of several parameters. These include the incidence of treatment-emergent adverse events (TEAEs), clinical laboratory evaluations such as hematology, blood chemistry, and urinalysis, vital signs, 12-lead electrocardiograms (ECGs) for clinically significant abnormalities, and findings from physical examinations. The study is designed to provide comprehensive data on the pharmacokinetics, safety, and tolerability of rezafungin acetate in the specified pediatric population.