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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Gram-Negative Bacterial Infections

Intervention / Treatment
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* Drug: Cefiderocol
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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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 Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Maximum Age: 3 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) |  | Up to 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Complicated urinary tract infection (cUTI), Complicated intra-abdominal infection (cIAI), Hospital-acquired bacterial pneumonia (HABP), Ventilator-associated (VABP), Bloodstream infection (BSI)/sepsis