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

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

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.

Study Overview

• Status: Completed
• Conditions: Gram-Negative Bacterial Infections
• Intervention / Treatment: Drug: Cefiderocol; Drug: Standard of Care

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa, 8000
      • Tygerberg hospital
• Taiwan
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital, Linkou Department of Pediatrics
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Eligibility Criteria: Key Inclusion Criteria:

1. Written informed consent has been provided by parent(s) or legally authorized representative(s) in accordance with local regulatory requirements
2. 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)
3. 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
4. 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:

1. Documented history of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antibiotic
2. Life expectancy of < 72 hours after enrollment
3. Urine output < 1.0 milliliter (mL)/kg/hour within the 24 hours prior to study drug administration on Day 1
4. 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
5. 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
6. Acute kidney injury based on an increase in serum creatinine ≥ 0.3 mg/dL within 48 hours from an established baseline value
7. 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
8. Receiving renal replacement therapy
9. Received any other investigational medicinal product within 30 days of study drug administration
10. Receiving treatment with a vasopressor at Screening
11. 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
12. 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
13. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shionogi
• Investigators: Study Director: Medical Director, Shionogi

Publications and helpful links

General Publications

• Bradley JS, Orchiston E, Portsmouth S, Ariyasu M, Baba T, Katsube T, Makinde O. Pharmacokinetics, Safety and Tolerability of Single-dose or Multiple-dose Cefiderocol in Hospitalized Pediatric Patients Three Months to Less Than Eighteen Years Old With Infections Treated With Standard-of-care Antibiotics in the PEDI-CEFI Phase 2 Study. Pediatr Infect Dis J. 2025 Feb 1;44(2):136-142. doi: 10.1097/INF.0000000000004529. Epub 2024 Sep 4.

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2024
• Primary Completion (Actual): March 31, 2025
• Study Completion (Actual): March 31, 2025

Study Registration Dates

• First Submitted: October 11, 2023
• First Submitted That Met QC Criteria: October 11, 2023
• First Posted (Actual): October 17, 2023

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Complicated urinary tract infection (cUTI); Complicated intra-abdominal infection (cIAI); Hospital-acquired bacterial pneumonia (HABP); Ventilator-associated (VABP); Bloodstream infection (BSI)/sepsis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Pathological Conditions, Signs and Symptoms; Sepsis; Gram-Negative Bacterial Infections; Health Services Administration; Health Care Quality, Access, and Evaluation; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quality of Health Care; Quality Indicators, Health Care; Amides; beta-Lactams; Lactams; Cephalosporins; Thiazines; Cefiderocol; Standard of Care
• Other Study ID Numbers: 1904R2136

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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