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

A Multicenter, Open-label, Single-arm, Multiple-dose Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Ceftobiprole Medocaril in Term and Pre-term Neonates and Infants up to 3 Months of Age With Late-onset Sepsis

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.

Study Overview

• Status: Completed
• Conditions: Neonatal Sepsis
• Intervention / Treatment: Drug: Ceftobiprole medocaril

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Montana, Bulgaria, 3400
    • MHAT Dr. Stamen Iliev AD Montana, Neonatology Department
  • Plovdiv, Bulgaria, 4000
    • UMHAT "Sveti Georgi" EAD, Pediatric surgery Clinic
  • Sofia, Bulgaria, 1407
    • "Acibadem City Clinic University Hospital Tokuda" EAD, Neonatology Department
• Estonia
  • Tallinn, Estonia, 13419
    • Tallinn Childrens' Hospital
• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 80337
      • Klinikum der Universität München, Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital
• Latvia
  • Riga, Latvia, 1002
    • Pauls Stradins Clinical University Hospital
  • Riga, Latvia, 1004
    • Children Clinical University Hospital - Neonatology Clinic
• Lithuania
  • Kaunas, Lithuania, 50161
    • Lithuanian Health Science University Hospital Kauno klinikos - Neonatology Clinic
  • Vilnius, Lithuania, 08410
    • Vilnius University Hospital Santaros klinikos - Neonatology Center
• Poland
  • Poznan, Poland, 60-535
    • Ginekologiczno-Położniczy Szpital Kliniczny im. Marcinkowskiego
  • Wroclaw, Poland, 50-556
    • Szpital Uniwersytecki - Klinika Neonatologii
• Slovakia
  • Martin, Slovakia, 03659
    • Univerzitna nemocnica MARTIN
• United States
  • Illinois
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Key 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm: Ceftobiprole; Ceftobiprole medocaril: 7.5 mg/kg to 15 mg/kg	Drug: Ceftobiprole medocaril; Ceftobiprole medocaril: 7.5 mg/kg every 12 hours to 15 mg/kg every 8 hours, administered IV as a 2-hour infusion.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Ceftobiprole, Ceftobiprole Medocaril, and Open-ring Metabolite	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	On treatment Day 3 prior to and 2, 4, and 8 hours after the start of the first ceftobiprole infusion of the day
Number of Patients With a Clinical Response	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	Up to 28 days
Number of Participants With Improved Signs and Symptoms of Late Onset Sepsis (LOS)	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.	Up to 28 days
Number of Patients With a Microbiological Response	Microbiological eradication or presumed eradication rate at the EOT and TOC visits.	Up to 28 days

Collaborators and Investigators

• Sponsor: Basilea Pharmaceutica
• Investigators: Study Director: Marc Engelhardt, MD, Basilea Pharmaceutica International Ltd, Allschwil

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2023
• Primary Completion (Actual): December 18, 2024
• Study Completion (Actual): December 18, 2024

Study Registration Dates

• First Submitted: April 17, 2023
• First Submitted That Met QC Criteria: May 3, 2023
• First Posted (Actual): May 12, 2023

Study Record Updates

• Last Update Posted (Actual): July 28, 2025
• Last Update Submitted That Met QC Criteria: July 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Infants; Neonates; Late-onset sepsis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Neonatal Sepsis; Sepsis; Toxemia; Anti-Bacterial Agents; Anti-Infective Agents; Ceftobiprole; Ceftobiprole medocaril
• Other Study ID Numbers: BPR-PIP-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No