A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Cefiderocol in Hospitalized Neonates and Infants

Sponsor

Shionogi (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06086626

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The primary purpose of this study is to understand the pharmacokinetics (PK) of single and multiple doses of cefiderocol in children from birth to less than 3 months of age with suspected or confirmed aerobic Gram-negative bacterial infections.

Condition or Disease	Intervention/Treatment	Phase
Gram-Negative Bacterial Infections	Drug: Cefiderocol Drug: Standard of Care	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Single-arm, Open-label Study to Assess the Pharmacokinetics, Safety, and Tolerability of Cefiderocol in Hospitalized Pediatric Patients From Birth to < 3 Months of Age With Suspected or Confirmed Aerobic Gram-negative Bacterial Infections

Anticipated Study Start Date :

Oct 31, 2023

Anticipated Primary Completion Date :

Apr 25, 2024

Anticipated Study Completion Date :

Aug 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single-Dose Cefiderocol Participants will receive a single dose cefiderocol on Day 1, along with standard of care antibiotics	Drug: Cefiderocol Administered via intravenous (IV) infusion Other Names: S-649266 Drug: Standard of Care Antibiotics selected by the investigator based on the participant's symptoms, in accordance with local standards
Experimental: Multiple-Dose Cefiderocol Participants will receive cefiderocol every 8 hours for 5 to 14 days, along with standard of care antibiotics	Drug: Standard of Care Antibiotics selected by the investigator based on the participant's symptoms, in accordance with local standards

Arm

Intervention/Treatment

Experimental: Single-Dose Cefiderocol

Participants will receive a single dose cefiderocol on Day 1, along with standard of care antibiotics

Drug: Cefiderocol

Administered via intravenous (IV) infusion

Other Names:

S-649266

Drug: Standard of Care

Antibiotics selected by the investigator based on the participant's symptoms, in accordance with local standards

Experimental: Multiple-Dose Cefiderocol

Participants will receive cefiderocol every 8 hours for 5 to 14 days, along with standard of care antibiotics

Drug: Standard of Care

Antibiotics selected by the investigator based on the participant's symptoms, in accordance with local standards

Outcome Measures

Primary Outcome Measures

Maximum Observed Plasma Concentration (Cmax) After a Single Dose of Cefiderocol [Up to 8 hours postdose]
Cmax After a Minimum of 4 Doses of Cefiderocol [Up to 8 hours postdose]
Area Under the Concentration-Time Curve Extrapolated From Time 0 to Infinity (AUC0-inf) After Single Dose of Cefiderocol [Up to 8 hours postdose]
Area Under the Concentration-Time Curve Over the Dosing Interval (AUC0-†) After a Minimum of 4 Doses of Cefiderocol [Up to 3 hours]
Terminal Elimination Half-Life (t1/2) After a Single Dose of Cefiderocol [Up to 8 hours postdose]
Terminal Elimination Half-Life (t1/2) After a Minimum of 4 Doses of Cefiderocol [Up to 8 hours postdose]

Secondary Outcome Measures

Number of Participants With Adverse Events (AEs) [Up to 28 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 3 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Eligibility Criteria: Key Inclusion Criteria:

Written informed consent has been provided by parent(s) or legally authorized representative(s) in accordance with local regulatory requirements
Hospitalized infants from birth to < 3 months (< 90 days) of age at the time written informed consent is provided. Enrollment of premature infants will not be restricted, but they must have a GA ≥ 26 weeks, PNA of 0 to 3 months, and weight of at least 1 kilogram (kg)
Require systemic IV antibiotic treatment for suspected or confirmed aerobic Gram-negative infections including, but not limited to, complicated urinary tract infection, complicated intra-abdominal infection, hospital-acquired/ ventilator-associated bacterial pneumonia, and BSI/sepsis
For the multiple-dose phase, within 72 hours of the start of potentially effective treatment with SOC antibiotics for the suspected or confirmed primary aerobic Gram-negative infection

Key Exclusion Criteria:

Documented history of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antibiotic
Life expectancy of < 72 hours after enrollment
Urine output < 1.0 milliliter (mL)/kg/hour within the 24 hours prior to study drug administration on Day 1
Serum creatinine value greater than the maximum for GA and PNA shown below within the 24 hours prior to study drug administration on Day 1
Neonatal acute kidney injury (AKI), defined as a serum creatinine level greater than 1.5 milligrams per decilieter (mg/dL) (133 micromoles[μmol]/liter [L]) or an increase of 0.3 mg/dL (17 to 27 μmol/L) per day from a previous lower value
Acute kidney injury based on an increase in serum creatinine ≥ 0.3 mg/dL within 48 hours from an established baseline value
Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the participant or the quality of the study data
Receiving renal replacement therapy
Received any other investigational medicinal product within 30 days of study drug administration
Receiving treatment with a vasopressor at Screening
Has a confirmed or strongly suspected infection at Screening with a pathogen known to be resistant to cefiderocol or only a Gram-positive pathogen or viral, fungal, or parasitic pathogen as the sole cause of infection
Anticipated need for antibacterial therapy longer than 14 days (example , osteomyelitis or endocarditis); this applies to both study treatment with cefiderocol, as well as adjunctive IV antibacterial treatment for suspected coinfection with Gram-positive organisms or multidrug resistant Gram-negative organisms
Suspected or confirmed central nervous system (CNS) infection, including suspected CNS infection who do not have a lumbar puncture (LP) but who are treated for potential CNS infection, evidence suggestive of CNS infection based on LP results (polymorphonuclear pleocytosis, hypoglycorrhachia, and increased protein concentration), regardless of culture results, LP with organisms on Gram stain or culture-positive cerebrospinal fluid