Late-onset Sepsis in Term and Pre-term Neonates and Infants up to 3 Months of Age
- Registration Number
- NCT05856227
- Lead Sponsor
- Basilea Pharmaceutica
- Brief Summary
This study will evaluate the safety, pharmacokinetics and efficacy of ceftobiprole in term and pre-term newborn babies and infants up to 3 months of age with late-onset sepsis (LOS). Ceftobiprole is an antibiotic which belongs to a group of medicines called 'cephalosporin antibiotics'. It is approved for its use to treat adults and children with pneumonia in many European and non-European countries.
- Detailed Description
This is a multicenter, open-label, single-arm, multiple-dose study of intravenous (IV) ceftobiprole medocaril (prodrug of the active moiety ceftobiprole). It may be combined with ampicillin and/or an aminoglycoside based on the Investigator's judgement according to manufacturer's instructions and/or local standard of care.
Following screening, ceftobiprole will be administered as a 2-hour infusion at a dose of 7.5 mg/kg every 12 hours to 15 mg/kg every 8 hours, depending on age and weight.
The target treatment duration is 7-10 days, which may be either extended to 14 days if considered clinically necessary by the Investigator or may be may be stopped after 5 days at the discretion of the Investigator based on resolution of signs and symptoms of sepsis and blood inflammation markers, in accordance with local standard of care.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 9
- Informed consent from parent(s) or other legally acceptable representative (LAR) to participate in the study
- Male or female, with a gestational age of ≥ 24 weeks and a post-natal age ranging from ≥ 3 days to ≤ 3 months
- Diagnosis of documented or presumed bacterial LOS requiring administration of systemic antibiotic treatment
- Sufficient vascular access to receive study drug and to allow blood sampling at a site separate from the study drug infusion line
Key
- Refractory septic shock not responding to 60 minutes of vasopressor treatment within 48 hours before enrollment
- Proven ventilator-associated pneumonia
- Proven central nervous system infection (e.g., meningitis, brain abscess)
- Proven osteomyelitis, infective endocarditis, or necrotising enterocolitis
- Impaired renal function or known significant renal disease, as evidenced by an estimated glomerular filtration rate (using the Schwartz formula or other applicable formula) calculated to be less than 2/3 of normal for the applicable age group, OR urinary output < 0.5 mL/kg/h (measured over at least 8 hours), OR requirement for dialysis
- Progressively fatal underlying disease, or life expectancy < 30 days
- Use of systemic antibacterial therapy for longer than 48 hours within 7 days before start of study medication
- Participation in another clinical study with an investigational product within 30 days of enrollment in the current study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Arm: Ceftobiprole Ceftobiprole medocaril Ceftobiprole medocaril: 7.5 mg/kg to 15 mg/kg
- Primary Outcome Measures
Name Time Method Safety and tolerability by incidence of adverse events (AEs) and serious adverse events (SAEs) Up to 5-7 weeks Descriptive statistics of AEs, SAEs, deaths, and discontinuations due to AEs during treatment with ceftobiprole
Number of participants with clinically relevant findings in laboratory tests Up to 5-7 weeks Descriptive statistics of clinical laboratory tests (including hematology, blood chemistry, urinalysis) and the change from baseline to each post-baseline visit value will also be summarized
Number of participants with clinically relevant findings in vital signs Up to 5-7 weeks Descriptive statistics of vital signs findings including body temperature, respiratory rate, pulse rate, and systolic and diastolic blood pressures
Number of participants with clinically relevant findings in physical examination Up to 5-7 weeks Descriptive statistics of physical examination findings including examination of general appearance, skin, head, neck, eyes, ears, nose, throat, cardiovascular system, thorax/lungs, abdomen, lymph nodes, extremities, and nervous system
- Secondary Outcome Measures
Name Time Method Observed plasma concentrations of ceftobiprole, ceftobiprole medocaril, and open-ring metabolite At day 3 Descriptive analyses of these concentrations will be summarised by timepoint for term and pre-term neonates with post-natal age up to 3 months.
Clinical response 5-7 weeks Clinical cure rate at the end of treatment (EOT) at day 3-14 and test of cure (TOC) at 7-14 days after last ceftobiprole dose visits in the Intent-to-Treat (ITT) and Clinically Evaluable (CE) populations
All-cause mortality through Day 28 All-cause mortality (ITT population)
Microbiological response 5-7 weeks Microbiological eradication or presumed eradication rate at the EOT and TOC visits (in the Microbiological Intent-to-Treat \[mITT\] and Microbiologically Evaluable \[ME\] populations)
Number of participants with improved signs and symptoms of LOS At the Day 3 and up to 5-7 weeks Improved signs and symptoms of LOS (including fever, hypothermia, abnormal heart rate, signs of impaired circulation, petechial rash or sclerema neonatorum, respiratory distress, gastrointestinal distress, irritability, lethargy and/or muscular or arterial hypotonia) will be assessed at Day 3, EOT, and TOC visits (ITT and CE populations)
Trial Locations
- Locations (14)
"Acibadem City Clinic University Hospital Tokuda" EAD, Neonatology Department
🇧🇬Sofia, Bulgaria
Tallinn Childrens' Hospital
🇪🇪Tallinn, Estonia
NorthShore University HealthSystem-Evanston Hospital
🇺🇸Evanston, Illinois, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
MHAT Dr. Stamen Iliev AD Montana, Neonatology Department
🇧🇬Montana, Bulgaria
UMHAT "Sveti Georgi" EAD, Pediatric surgery Clinic
🇧🇬Plovdiv, Bulgaria
Klinikum der Universität München, Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital
🇩🇪Munich, Bavaria, Germany
Pauls Stradins Clinical University Hospital
🇱🇻Riga, Latvia
Children Clinical University Hospital - Neonatology Clinic
🇱🇻Riga, Latvia
Lithuanian Health Science University Hospital Kauno klinikos - Neonatology Clinic
🇱🇹Kaunas, Lithuania
Vilnius University Hospital Santaros klinikos - Neonatology Center
🇱🇹Vilnius, Lithuania
Ginekologiczno-Położniczy Szpital Kliniczny im. Marcinkowskiego
🇵🇱Poznan, Poland
Szpital Uniwersytecki - Klinika Neonatologii
🇵🇱Wroclaw, Poland
Univerzitna nemocnica Martin
🇸🇰Martin, Slovakia