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

NCT04335539 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 1802R21352019-002120-32
• Study Type: interventional
• Target: 53
• Locations: 8 countries
• Sites: 21

Brief Summary

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

Conditions

Bloodstream Infections (BSI); Gram-negative Bacterial Infections; Complicated Intra-abdominal Infection (cIAI); Hospital Acquired Pneumonia (HAP); Ventilator-acquired Pneumonia; Complicated Urinary Tract Infection (cUTI); Sepsis

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (2)

• Multiple-Dose Phase: Number of Participants With a Clinical Outcome, as Assessed by the Investigator

  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

  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])

Study Arms (2)

Single Dose Phase: Cefiderocol

EXPERIMENTAL

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; Drug: Standard of Care

Multiple Dose Phase: Cefiderocol

EXPERIMENTAL

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; Drug: Standard of Care

Interventions

Cefiderocol DRUG

Administered intravenously over 3 hours

Also known as: S-649266, Fetroja

Multiple Dose Phase: Cefiderocol; Single Dose Phase: Cefiderocol

Standard of Care DRUG

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.

Multiple Dose Phase: Cefiderocol; Single Dose Phase: Cefiderocol

Eligibility Criteria

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

You may qualify if:

• Participant's parent(s) or legally authorized representative (LAR) provides written informed consent in accordance with regional and country-specific laws and regulations.
• 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).
• 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.
• 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.
• 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.

You may not qualify if:

• 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).
• Multiple-dose only: Participant has an infection caused only by a confirmed Gram-positive pathogen.
• 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).
• Participant has cystic fibrosis.
• 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.
• Participant has end-stage renal disease (ESRD), is on hemodialysis (HD), or receiving continuous venovenous hemofiltration (CVVH).
• Participant has experienced shock in the prior month or is in shock at the time of Screening.
• Participant has severe neutropenia or is severely immunocompromised.
• Participant has multiorgan failure.
• Participant has a life expectancy of \< 30 days due to severity of a concurrent illness.
• Participant is a female who has a positive pregnancy test at Screening.
• Participant is a female who is breastfeeding.
• Participant has received any other investigational medicinal product (IMP) within 30 days.
• 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.

Sponsors & Collaborators

• Shionogi: lead

Study Sites (23)

Universitair Ziekenhuis Brussel

Brussels, 1200, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Tallinn Childrens Hospital

Tallinn, Estonia

Location

Tartu Ulikooli Kliinikum - Anestesioloogia ja Intensiivravi Kliinik

Tartu, Estonia

Location

JSC "Medical Corporation Evex" " M. Iashvili Batumi Maternal and Child Central Hospital"

Batumi, Georgia

Location

JSC "EVEX Medical Corporation"- M Lashvili Childrens Central Hospital

Tbilisi, Georgia

Location

Ltd Unimedi Kakheti Childrens New Clinic

Tbilisi, Georgia

Location

Heim Pl Orszgos Gyermekgygyszati Intzet

Pilisborosjenő, Hungary

Location

Szegedi Tudomnyegyetem

Szegedi Tudomnyegyetem, Hungary

Location

Daugavpils regional Hospital

Daugavpils, Latvia

Location

Bernu Kliniska Universitates Slimnica Childrens Hospital - Tornakalna

Riga, Latvia

Location

St. Petersburg State Pediatric Medical University

Saint Petersburg, Russia

Location

Smolensk State Medical University

Smolensk, Russia

Location

Hospital Germans Trias i Pujol

Barcelona, Spain

Location

Hospital Universitario y Politecnico La Fe

Valencia, Spain

Location

King Chulalongkorn Memorial Hospital, Chulalongkorn University

Bangkok, Thailand

Location

Siriraj Hospital

Bangkok Noi, Thailand

Location

PHPT-Chiangrai PrachanuKroh Hospital

Chiang Mai, Thailand

Location

Khon Kaen University (KKU) - Faculty of Medicine-Srinagarind Hospital

Khon Kaen, Thailand

Location

Dnipropetrovsk Regional Children Clinical Hospital

Kharkiv, Ukraine

Location

Regional Children Clinical Hospital

Kharkiv, Ukraine

Location

National Childrens Specialized Hospital OHMATDYT of the Ministry of Health of Ukraine

Kiev, Ukraine

Location

Higher State Educational Institute of Ukraine Ukrainian Medical Stamatological Academy

Poltava, Ukraine

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; Healthcare-Associated Pneumonia; Pneumonia, Ventilator-Associated

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; Cross Infection; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes

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

Results Point of Contact

• Title: Shionogi Clinical Trials Administrator Clinical Support Help Line
• Organization: Shionogi Inc.

shionogiclintrials-admin@shionogi.co.jp

800-849-9707

Study Officials

• Shionogi Clinical Trials Administrator Clinical Support Help Line

  Shionogi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: April 3, 2020
• First Posted: April 6, 2020
• Study Start: August 21, 2020
• Primary Completion: February 6, 2023
• Study Completion: February 6, 2023
• Last Updated: February 27, 2026
• Results First Posted: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

TH (4); GE (3); UA (4); LA (2); HU (2); ES (2); RU (2); BE (2)