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

NCT06086626 | Completed Phase 2 FDA Drug

• 1 other identifier: 1904R2136
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 4

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.

Conditions

Gram-Negative Bacterial Infections

Keywords

Complicated urinary tract infection (cUTI); Complicated intra-abdominal infection (cIAI); Hospital-acquired bacterial pneumonia (HABP); Ventilator-associated (VABP); Bloodstream infection (BSI)/sepsis

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (1)

• Number of Participants With Adverse Events (AEs)

  Up to 28 days

Study Arms (2)

Single-Dose Cefiderocol

EXPERIMENTAL

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

Drug: Cefiderocol; Drug: Standard of Care

Multiple-Dose Cefiderocol

EXPERIMENTAL

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

Drug: Standard of Care

Interventions

Cefiderocol DRUG

Administered via intravenous (IV) infusion

Also known as: S-649266

Single-Dose Cefiderocol

Standard of Care DRUG

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

Multiple-Dose Cefiderocol; Single-Dose Cefiderocol

Eligibility Criteria

• Age: Up to 3 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shionogi: lead

Study Sites (4)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Tygerberg Hospital

Cape Town, Western Cape, 8000, South Africa

Location

Chang Gung Memorial Hospital, Linkou Department of Pediatrics

Taoyuan, 333, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 39230271 DERIVED

MeSH Terms

Conditions

Gram-Negative Bacterial Infections; Sepsis

Interventions

Cefiderocol; Standard of Care

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Medical Director

  Shionogi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2023
• First Posted: October 17, 2023
• Study Start: March 14, 2024
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); ZA (1); TW (1)