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 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.

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Marc Engelhardt, MD; Phone Number: +41 79 701 0551; Email: marc.engelhardt@basilea.com
• Study Contact Backup: Name: Manuel Häckl, MD; Phone Number: +41 615671533; Email: manuel.haeckl@basilea.com

Study Locations

• Bulgaria
  • Montana, Bulgaria, 3400
    • Recruiting
    • MHAT Dr. Stamen Iliev AD Montana, Neonatology Department
  • Plovdiv, Bulgaria, 4000
    • Recruiting
    • UMHAT "Sveti Georgi" EAD, Pediatric surgery Clinic
  • Sofia, Bulgaria, 1407
    • Recruiting
    • "Acibadem City Clinic University Hospital Tokuda" EAD, Neonatology Department
• Estonia
  • Tallinn, Estonia, 13419
    • Recruiting
    • Tallinn Childrens' Hospital
• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 80337
      • Recruiting
      • Klinikum der Universität München, Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital
• Latvia
  • Riga, Latvia, 1002
    • Recruiting
    • Pauls Stradins Clinical University Hospital
  • Riga, Latvia, 1004
    • Recruiting
    • Children Clinical University Hospital - Neonatology Clinic
• Lithuania
  • Kaunas, Lithuania, 50161
    • Recruiting
    • Lithuanian Health Science University Hospital Kauno klinikos - Neonatology Clinic
  • Vilnius, Lithuania, 08410
    • Recruiting
    • Vilnius University Hospital Santaros klinikos - Neonatology Center
• Poland
  • Poznan, Poland, 60-535
    • Recruiting
    • Ginekologiczno-Położniczy Szpital Kliniczny im. Marcinkowskiego
  • Wroclaw, Poland, 50-556
    • Recruiting
    • Szpital Uniwersytecki - Klinika Neonatologii
• Slovakia
  • Martin, Slovakia, 03659
    • Recruiting
    • Univerzitna Nemocnica Martin
• United States
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Recruiting
      • NorthShore University HealthSystem-Evanston Hospital
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Recruiting
      • 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 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 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
Safety and tolerability by incidence of adverse events (AEs) and serious adverse events (SAEs)	Descriptive statistics of AEs, SAEs, deaths, and discontinuations due to AEs during treatment with ceftobiprole	Up to 5-7 weeks
Number of participants with clinically relevant findings in laboratory tests	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	Up to 5-7 weeks
Number of participants with clinically relevant findings in vital signs	Descriptive statistics of vital signs findings including body temperature, respiratory rate, pulse rate, and systolic and diastolic blood pressures	Up to 5-7 weeks
Number of participants with clinically relevant findings in physical examination	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	Up to 5-7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observed plasma concentrations of ceftobiprole, ceftobiprole medocaril, and open-ring metabolite	Descriptive analyses of these concentrations will be summarised by timepoint for term and pre-term neonates with post-natal age up to 3 months.	At day 3
Clinical response	Clinical cure rate at the end of treatment (EOT) at day 7-14 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	5-7 weeks
All-cause mortality	All-cause mortality (ITT population)	through Day 28
Microbiological response	Microbiological eradication or presumed eradication rate at the EOT and TOC visits (in the Microbiological Intent-to-Treat [mITT] and Microbiologically Evaluable [ME] populations)	5-7 weeks
Number of participants with improved signs and symptoms of 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) will be assessed at Day 3, EOT, and TOC visits (ITT and CE populations)	At the Day 3 and up to 5-7 weeks

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 (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 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): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

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; Sepsis; Toxemia; Neonatal Sepsis; Anti-Infective Agents; Anti-Bacterial Agents; Ceftobiprole; Ceftobiprole medocaril
• Other Study ID Numbers: BPR-PIP-003

Drug and device information, study documents

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