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

Neonatal Sepsis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05856227
• Other study ID #: BPR-PIP-003
• Status: Recruiting
• Phase: Phase 3
• Start date: August 6, 2023
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Basilea Pharmaceutica
• Contact: Marc Engelhardt, MD
• Phone: +41 79 701 0551
• Email: marc.engelhardt[@]basilea.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Days to 3 Months

Eligibility

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

Related Conditions & MeSH terms

• Neonatal Sepsis
• Sepsis
• Toxemia

Intervention

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.

Locations

Country	Name	City	State
Bulgaria	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
Estonia	Tallinn Childrens' Hospital	Tallinn
Germany	Klinikum der Universität München, Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital	Munich	Bavaria
Latvia	Children Clinical University Hospital - Neonatology Clinic	Riga
Latvia	Pauls Stradins Clinical University Hospital	Riga
Lithuania	Lithuanian Health Science University Hospital Kauno klinikos - Neonatology Clinic	Kaunas
Lithuania	Vilnius University Hospital Santaros klinikos - Neonatology Center	Vilnius
Poland	Ginekologiczno-Polozniczy Szpital Kliniczny im. Marcinkowskiego	Poznan
Poland	Szpital Uniwersytecki - Klinika Neonatologii	Wroclaw
Slovakia	Univerzitna nemocnica Martin	Martin
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	West Virginia University	Morgantown	West Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Basilea Pharmaceutica

Countries where clinical trial is conducted

United States,  Bulgaria,  Estonia,  Germany,  Latvia,  Lithuania,  Poland,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	All-cause mortality	All-cause mortality (ITT population)	through Day 28
Secondary	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
Secondary	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