Late-onset Sepsis in Term and Pre-term Neonates and Infants up to 3 Months of Age

Phase 3

Completed

Brief Summary: This study evaluated 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 was a multicenter, open-label, single-arm, multiple-dose study of intravenous (IV) ceftobiprole medocaril (prodrug of the active moiety ceftobiprole). It could 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 was 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 was 3-10 days, which could be extended to 14 days if considered clinically necessary by the Investigator.

Recruitment & Eligibility

Inclusion Criteria

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

Exclusion Criteria

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 necrotizing 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 72 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

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
Number of Patients With Adverse Events (AEs)	Up to 5-7 weeks	Number of patients with AEs, serious adverse events (SAEs), AEs leading to discontinuations and AEs of special interest

Secondary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax) of Ceftobiprole, Ceftobiprole Medocaril, and Open-ring Metabolite	On treatment Day 3 prior to and 2, 4, and 8 hours after the start of the first ceftobiprole infusion of the day	Observed pharmacokinetic parameter Cmax of ceftobiprole (the active moiety), its pro-drug ceftobiprole medocaril and the open-ring metabolite in term and pre-term neonates with post-natal age up to 3 months
Number of Patients With a Clinical Response	Up to 28 days	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) population
Number of Participants With Improved Signs and Symptoms of Late Onset Sepsis (LOS)	Up to 28 days	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) assessed at Day 3, EOT, and TOC visits (ITT) populations.
Number of Patients With a Microbiological Response	Up to 28 days	Microbiological eradication or presumed eradication rate at the EOT and TOC visits.

Locations (14): 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
"Acibadem City Clinic University Hospital Tokuda" EAD, Neonatology Department
🇧🇬
Sofia, Bulgaria
Tallinn Childrens' Hospital
🇪🇪
Tallinn, Estonia
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
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NorthShore University HealthSystem-Evanston Hospital
🇺🇸Evanston, Illinois, United States