This study aimed to learn what levels of rezafungin were in the blood after dosing and how safe it was, in children and adolescents below 18 years old who were already receiving treatment for a fungal infection, a suspected fungal infection or at risk of fungal infection. The main question the researchers wanted to answer in this trial was: • What were the levels of rezafungin in the blood after the participants were dosed? The researchers also wanted to know what medical problems happened during this trial. The participants in this trial received one dose of rezafungin on day 1 through a needle into a vein, called an intravenous (IV) infusion. The dose of rezafungin was measured in milligrams (mg) and given to the participants according to their body weight in kilograms (mg/kg). The doctors checked the participants' health and asked questions about what medications they were taking and took blood samples to check the levels of rezafungin in the participants' blood. After receiving the treatment at day 30, the doctors checked the participants' health. This was an "open-label" trial. This means each participant knew what they were receiving, and the doctors and trial staff also knew.
To date, there are no clinical studies evaluating rezafungin in paediatric subjects. The primary objective of the trial was to evaluate the pharmacokinetics (PK) of a single intravenous (IV) dose of rezafungin in paediatric participants from birth to \< 18 years, receiving concomitant systemic antifungals as prophylaxis for invasive fungal infection (IFI) or to treat a suspected or confirmed fungal infection. The secondary objective was to assess the safety and tolerability of a single IV dose of rezafungin in the subjects. This is a Phase 1, multicentre, open-label, single-dose study. The study will be conducted at approximately 10 sites across at least 3 countries in Europe. The study will be conducted in 3 parts: * Part 1 will include subjects aged 12 to \<18 years (Group 1) * Part 2 will include subjects aged 6 to \<12 years (Group 2), and subjects aged 2 to \<6 years (Group 3). * Part 3 will include subjects from birth to \<2 years (Group 4) The study design for the 3 parts is similar and comprises a Screening (pre-treatment) period from Day -3 to Day -1, Dosing on Day 1 (single IV infusion of rezafungin) followed by multiple PK sampling, and a Follow up visit on Day 30 (± 5 days). PK sampling will be performed at specified timepoints for each group. Limitations and Caveats Due to recruitment challenges, the study was terminated following enrollment of 2 participants aged between 12-17 years in Group 1 (Part 1). Group 2, 3 (Part 2) and Group 4 (Part 3) were not initiated prior to study termination. Due to the low number of participants in this study, baseline characteristics, outcome measure results and adverse events have not been reported to reduce the potential of re-identification.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
This is a Phase 1, multicentre, open-label, single-dose study. The study will be conducted at 10 sites across at least 3 countries in Europe.
Universitätsklinikum Essen Zentrum für Kinder- und Jugendmedizin
Essen, Germany
Universitätsklinikum Frankfurt, Goethe Universität Klinik für Kinder- und Jugendmedizin
Frankfurt, Germany
Universitätsklinikum Münster Klinik für Kinder- und Jugendmedizin
Münster, Germany
Hospital Universitario de Burgos
Burgos, Spain
Hospital Universitario 12 de Octubre.
Madrid, Spain
Hospital Universitario La Paz
Madrid, Spain
Great Ormond Street Hospital for Children NHS Foundation Trust
London, United Kingdom
Saint Mary's Hospital, Imperial College Healthcare NHS Trust
London, United Kingdom
St. George's University Hospitals, NHS Foundation Trust
London, United Kingdom
Southampton General Hospital, University Hospital Southampton NHS Foundation Trust
Southampton, United Kingdom
Maximum Observed Plasma Concentration (Cmax) of Rezafungin
Blood samples of 1 mL each were collected for the analysis of rezafungin plasma concentration. PK parameters were determined from the rezafungin concentration-time data using non-compartmental methods and actual sampling times.
Time frame: At end-of-infusion ± 15 minutes, then between 3 and 4 hours after start of infusion, between 6 and 8 hours after start of infusion, at 48 hours (± 4 hours) after start of infusion, and at 168 hours (± 12 hours) after start of infusion
Time at which the Cmax of Rezafungin Was Observed (Tmax)
Blood samples of 1 mL each were collected for the analysis of rezafungin plasma concentration. PK parameters were determined from the rezafungin concentration-time data using non-compartmental methods and actual sampling times.
Time frame: End of infusion and 3-4, 6-8, 48, and 168 hours after start of infusion
Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t) of Rezafungin
Blood samples of 1 mL each were collected for the analysis of rezafungin plasma concentration. PK parameters were determined from the rezafungin concentration-time data using non-compartmental methods and actual sampling times.
Time frame: End of infusion and 3-4, 6-8, 48, and 168 hours after start of infusion
Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of Rezafungin
Blood samples of 1 mL each were collected for the analysis of rezafungin plasma concentration. PK parameters were determined from the rezafungin concentration-time data using non-compartmental methods and actual sampling times.
Time frame: End of infusion and 3-4, 6-8, 48, and 168 hours after start of infusion
Total Clearance (CL) of Rezafungin
Blood samples of 1 mL each were collected for the analysis of rezafungin plasma concentration. PK parameters were determined from the rezafungin concentration-time data using non-compartmental methods and actual sampling times.
Time frame: End of infusion and 3-4, 6-8, 48, and 168 hours after start of infusion
Volume of Distribution of Rezafungin at Steady-state (Vss)
Blood samples of 1 mL each were collected for the analysis of rezafungin plasma concentration. PK parameters were determined from the rezafungin concentration-time data using non-compartmental methods and actual sampling times.
Time frame: End of infusion and 3-4, 6-8, 48, and 168 hours after start of infusion
Apparent Volume of Distribution of Rezafungin During the Terminal Phase (Vz)
Blood samples of 1 mL each were collected for the analysis of rezafungin plasma concentration. PK parameters were determined from the rezafungin concentration-time data using non-compartmental methods and actual sampling times.
Time frame: End of infusion and 3-4, 6-8, 48, and 168 hours after start of infusion
Terminal Elimination Half-life of Rezafungin (t1/2)
Blood samples of 1 mL each were collected for the analysis of rezafungin plasma concentration. PK parameters were determined from the rezafungin concentration-time data using non-compartmental methods and actual sampling times.
Time frame: End of infusion and 3-4, 6-8, 48, and 168 hours after start of infusion
Incidence of treatment-emergent adverse events (TEAEs)
A TEAE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of rezafungin, whether or not considered related to the rezafungin that was not present prior to the administration of rezafungin or any event present that worsened in either severity or frequency following exposure to rezafungin. Clinically significant changes in laboratory evaluations (including haematology, blood chemistry and urinalysis), vital signs, 12-lead electrocardiogram (ECG) and physical examination findings were also reported as TEAEs.
Time frame: From start of study on Day 1 to follow up Day 30 (+/- days)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.