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

Sponsor

Basilea Pharmaceutica (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05856227

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patient Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neonatal Sepsis	Drug: Ceftobiprole medocaril	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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 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
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Days to 3 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles, Department of Pediatrics	Los Angeles	California	United States	90095
2	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
3	West Virginia University	Morgantown	West Virginia	United States	26506
4	MHAT Dr. Stamen Iliev AD Montana, Neonatology Department	Montana		Bulgaria	3400
5	UMHAT "Sveti Georgi" EAD, Pediatric surgery Clinic	Plovdiv		Bulgaria	4000
6	"Acibadem City Clinic University Hospital Tokuda" EAD, Neonatology Department	Sofia		Bulgaria	1407
7	Tallinn Childrens' Hospital	Tallinn		Estonia	13419
8	Klinikum der Universität München, Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital	Munich	Bavaria	Germany	80337
9	Pauls Stradins Clinical University Hospital	Riga		Latvia	1002
10	Children Clinical University Hospital - Neonatology Clinic	Riga		Latvia	1004
11	Lithuanian Health Science University Hospital Kauno klinikos - Neonatology Clinic	Kaunas		Lithuania	50161
12	Vilnius University Hospital Santaros klinikos - Neonatology Center	Vilnius		Lithuania	08410
13	Ginekologiczno-Położniczy Szpital Kliniczny im. Marcinkowskiego	Poznan		Poland	60-535
14	Szpital Uniwersytecki - Klinika Neonatologii	Wroclaw		Poland	50-556
15	Univerzitna nemocnica Martin	Martin		Slovakia	03659