A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of Cefiderocol in Hospitalized Pediatric Participants

A Single Arm, Open-label Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of Cefiderocol in Hospitalized Paediatric Subjects 3 Months to <18 Years of Age With Suspected or Confirmed Aerobic Gram-negative Bacterial Infections

The primary objectives of this study are:

• To assess the safety and tolerability of cefiderocol after single-dose administration in hospitalized paediatric participants 3 months to < 18 years of age with suspected or confirmed aerobic Gram-negative bacterial infections
• To assess the pharmacokinetics (PK) of cefiderocol after single-dose administration of cefiderocol in hospitalized paediatric participants 3 months to < 18 years of age with suspected or confirmed aerobic Gram-negative bacterial infections
• To assess the safety and tolerability of cefiderocol after multiple-dose administration in hospitalized paediatric participants 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections
• To assess the PK of cefiderocol after multiple-dose administration in hospitalized paediatric participants 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections

Study Overview

• Status: Completed
• Conditions: Sepsis; Gram-negative Bacterial Infections; Bloodstream Infections (BSI); Complicated Intra-abdominal Infection (cIAI); Hospital Acquired Pneumonia (HAP); Ventilator-acquired Pneumonia; Complicated Urinary Tract Infection (cUTI)
• Intervention / Treatment: Drug: Cefiderocol; Drug: Standard of Care

Detailed Description

This is a multicenter, single-arm, open-label, single- and multiple-dose study to assess the safety, tolerability, and PK of cefiderocol in hospitalized paediatric participants.

The single-dose phase will include 4 separate cohorts of participants, grouped according to age range:

• Cohort 1: 12 to < 18 years
• Cohort 2: 6 to < 12 years
• Cohort 3: 2 to < 6 years
• Cohort 4: 3 months to < 2 years Cohorts 1, 2, and 3 in the single-dose phase will be initiated in parallel. Cohort 4 will begin after safety and PK data from at least 6 participants from the single-dose Cohorts 1, 2, and 3 (with a minimum of 3 participants from Cohort 3) have been assessed.

The multiple-dose phase will include 3 cohorts according to age range (Cohorts 2, 3, and 4) and will begin after safety and PK data from 6 participants in the corresponding single-dose cohort have been assessed.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Cliniques Universitaires Saint-Luc
  • Brussels, Belgium, 1200
    • Universitair Ziekenhuis Brussel
• Estonia
  • Tallinn, Estonia
    • Tallinn Childrens Hospital
  • Tartu, Estonia
    • Tartu Ulikooli Kliinikum - Anestesioloogia ja Intensiivravi Kliinik
• Georgia
  • Batumi, Georgia
    • JSC "Medical Corporation Evex" " M. Iashvili Batumi Maternal and Child Central Hospital"
  • Tbilisi, Georgia
    • JSC "EVEX Medical Corporation"- M Lashvili Childrens Central Hospital
  • Tbilisi, Georgia
    • Ltd Unimedi Kakheti Childrens New Clinic
• Hungary
  • Pilisborosjenő, Hungary
    • Heim Pl Orszgos Gyermekgygyszati Intzet
  • Szegedi Tudomnyegyetem, Hungary
    • Szegedi Tudomnyegyetem
• Latvia
  • Daugavpils, Latvia
    • Daugavpils Regional Hospital
  • Riga, Latvia
    • Bernu Kliniska Universitates Slimnica Childrens Hospital - Tornakalna
• Russia
  • Saint Petersburg, Russia
    • St. Petersburg State Pediatric Medical University
  • Smolensk, Russia
    • Smolensk State Medical University
• Spain
  • Barcelona, Spain
    • Hospital Germans Trias i Pujol
  • Valencia, Spain
    • Hospital Universitario y Politécnico La Fe
• Thailand
  • Bangkok, Thailand
    • King Chulalongkorn Memorial Hospital, Chulalongkorn University
  • Bangkok Noi, Thailand
    • Siriraj Hospital
  • Chiang Mai, Thailand
    • PHPT-Chiangrai PrachanuKroh Hospital
  • Khon Kaen, Thailand
    • Khon Kaen University (KKU) - Faculty of Medicine-Srinagarind Hospital
• Ukraine
  • Kharkiv, Ukraine
    • Dnipropetrovsk Regional Children Clinical Hospital
  • Kharkiv, Ukraine
    • Regional Children Clinical Hospital
  • Kiev, Ukraine
    • National Childrens Specialized Hospital OHMATDYT of the Ministry of Health of Ukraine
  • Poltava, Ukraine
    • Higher State Educational Institute of Ukraine Ukrainian Medical Stamatological Academy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant's parent(s) or legally authorized representative (LAR) provides written informed consent in accordance with regional and country-specific laws and regulations.
2. Participant provides written informed assent, when feasible (age of assent to be determined by institutional review boards/independent ethics committees [IRB's/IEC's] or be consistent with local legal requirements).
3. Hospitalized participant is 3 months to <18 years of age at the time written informed consent/assent is obtained for the single-dose phase. Hospitalized participant is 3 months to <12 years of age at the time written informed consent/assent is obtained for the multiple-dose phase. Premature babies will not be restricted, but the participant must have an adjusted or postnatal age of 3 months.
4. Participant has a suspected or confirmed infection (including but not limited to complicated urinary tract infection [cUTI], complicated intra-abdominal infection [cIAI], hospital-acquired pneumonia [HAP] /ventilator-acquired pneumonia [VAP], sepsis, or bloodstream infections [BSI]) that requires hospitalization for treatment with IV antibiotics.
5. If participant is a sexually active female of childbearing potential and has reached menarche or Tanner stage 3, participant agrees to use barrier contraception (including condom, diaphragm, or cervical cap) with spermicide or agrees to use a highly effective method of contraception (including contraceptive implant, injectable contraceptive, combination oral contraceptive, or an intrauterine [IUD] contraceptive device) from Screening up to 28 days after administration of the last dose of cefiderocol.

Exclusion Criteria:

1. Participant has a documented history of any hypersensitivity or allergic reaction to any β-lactam antibiotic (Note: for β-lactams, a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment).
2. Multiple-dose only: Participant has an infection caused only by a confirmed Gram-positive pathogen.
3. Participant has a suspected or confirmed central nervous system (CNS) infection (eg, meningitis, brain abscess, shunt infection) or osteomyelitis (which would require prolonged antibiotic therapy).
4. Participant has cystic fibrosis.

5. Single-dose phase: Participant has moderate or severe renal impairment based on estimated glomerular filtration rate (eGFR) (based on Schwartz equation if ≥ 3 months to < 1 year of age and modified Bedside Schwartz equation if ≥ 1 to < 18 years of age) of < 60 milliliter (mL) per minute (min)/1.73 ^2² at Screening.

   Multiple-dose phase: Participant has an eGFR (based on Schwartz equation if ≥ 3 months to < 1 year of age and modified Bedside Schwartz equation if ≥ 1 to < 18 years of age) of < 15 mL/min/1.73 ^2² at Screening.

6. Participant has end-stage renal disease (ESRD), is on hemodialysis (HD), or receiving continuous venovenous hemofiltration (CVVH).
7. Participant has experienced shock in the prior month or is in shock at the time of Screening.
8. Participant has severe neutropenia or is severely immunocompromised.
9. Participant has multiorgan failure.
10. Participant has a life expectancy of < 30 days due to severity of a concurrent illness.
11. Participant is a female who has a positive pregnancy test at Screening.
12. Participant is a female who is breastfeeding.
13. Participant has received any other investigational medicinal product (IMP) within 30 days.
14. Participant has 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, including acute trauma to the pelvis or urinary tract.
15. Participant is receiving vasopressor therapy at Screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Dose Phase: Cefiderocol; Participants will receive a single dose of cefiderocol administered intravenously (IV) on Day 1, in addition to standard of care. Participants weighing less than 34 kilograms (kg) will receive 60 milligrams (mg)/kg of cefiderocol and participants ≥34 kg will receive 2000 mg.	Drug: Cefiderocol; Administered intravenously over 3 hours; Other Names: S-649266; Fetroja; Drug: Standard of Care; Standard of care antibiotics will be selected by the investigator based on the suspected or confirmed pathogen(s) for the infection in accordance with local standards.
Experimental: Multiple Dose Phase: Cefiderocol; Participants will receive cefiderocol administered via IV every 8 hours on Day 1 and continuing for 5 to 14 days in addition to standard of care. Participants weighing less than 34 kg will receive 60 mg/kg of cefiderocol and participants ≥34 kg will receive 2000 mg. Dosage may be adjusted based on renal function.	Drug: Cefiderocol; Administered intravenously over 3 hours; Other Names: S-649266; Fetroja; Drug: Standard of Care; Standard of care antibiotics will be selected by the investigator based on the suspected or confirmed pathogen(s) for the infection in accordance with local standards.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single-Dose Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as AEs reported after the initial dose of study drug. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.	Day 1 up to Day 28
Multiple-Dose Phase: Number of Participants With TEAEs	An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as AEs reported after the initial dose of study drug. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.	Day 1 up to Day 42
Single Dose Phase: Maximum Observed Plasma Concentration (Cmax) of Cefiderocol		Up to 8 hours postdose
Single Dose Phase: Area Under the Plasma Concentration Time Curve Extrapolated From Time 0 to Infinity (AUCinf) of Cefiderocol		Up to 8 hours postdose
Single Dose Phase: Apparent Terminal Elimination Half-life (t1/2) of Cefiderocol		Up to 8 hours postdose
Multiple Dose Phase: Cmax of Cefiderocol		Up to 8 hours postdose
Multiple Dose Phase: Area Under the Plasma Concentration Time Curve Extrapolated From Time 0 to the Last Measurable Concentration (AUC0-t) of Cefiderocol		Up to 8 hours postdose
Multiple Dose Phase: t1/2 of Cefiderocol		Up to 8 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multiple-Dose Phase: Number of Participants With a Clinical Outcome, as Assessed by the Investigator	The clinical outcomes were clinical cure, clinical failure, and indeterminate. Clinical Cure: Resolution or substantial improvement of baseline signs and symptoms. Participants with bacteremia must have had eradication of bacteremia caused by the Gram-negative pathogen. Clinical Failure: No apparent response to therapy; persistence or worsening of baseline signs and/or symptoms, reappearance of signs and/or symptoms; development of new signs and/or symptoms requiring antibiotic therapy other than, or in addition to, study treatment therapy; or death due to pneumonia/complicated intra-abdominal infection (cIAI) or complicated urinary tract infections (cUTI) or bloodstream infection (BSI)/sepsis. Indeterminate: Lost to follow-up such that a determination of clinical cure/failure could not be made.	End of treatment (EOT; up to Day 14), post-treatment (7 days after EOT [up to Day 21]), and end of study (EOS; 28 days after last dose [up to Day 42])
Multiple-Dose Phase: Number of Participants With a Microbiological Outcome, as Assessed by the Investigator	Microbiological outcomes were eradication, persistence, and indeterminate. For hospital-acquired pneumonia (HAP)/ventilator-acquired pneumonia (VAP)/cIAI and BSI/sepsis- Eradication: Absence of baseline Gram-negative pathogen from an appropriate clinical specimen; Persistence: Continued presence of baseline Gram-negative pathogen from an appropriate clinical specimen; Indeterminate: No culture obtained from an appropriate clinical specimen or additional antibiotic therapy for the treatment of current infection including missed sampling. For cUTI- Eradication: A urine culture showed baseline Gram-negative uropathogen found at entry at ≥10^5 colony forming units (CFU)/milliliters (mL) was reduced to <10^3 CFU/mL; Persistence: A urine culture showed that the baseline Gram-negative uropathogen found at entry at ≥10^5 CFU/mL remained at ≥10^3 CFU/mL; Indeterminate: No urine culture obtained or additional antibiotic therapy for the treatment of current infection including missed sampling.	EOT (up to Day 14), post-treatment (7 days after EOT [up to Day 21]), and EOS (28 days after last dose [up to Day 42])

Collaborators and Investigators

• Sponsor: Shionogi
• Investigators: Study Director: Shionogi Clinical Trials Administrator Clinical Support Help Line, 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): August 21, 2020
• Primary Completion (Actual): February 6, 2023
• Study Completion (Actual): February 6, 2023

Study Registration Dates

• First Submitted: April 3, 2020
• First Submitted That Met QC Criteria: April 3, 2020
• First Posted (Actual): April 6, 2020

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Lung Diseases; Pneumonia; Bacterial Infections; Bacterial Infections and Mycoses; Cross Infection; Iatrogenic Disease; Pathological Conditions, Signs and Symptoms; Healthcare-Associated Pneumonia; Sepsis; Pneumonia, Ventilator-Associated; 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: 1802R2135; 2019-002120-32 (EudraCT Number)

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
• product manufactured in and exported from the U.S.: No