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Gram-negative Bacterial InfectionsPhase 2NCT04335539

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

A Phase 2 study testing Cefiderocol in people with Gram-negative Bacterial Infections and Bloodstream Infections (BSI), run by Shionogi at 23 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 3 months to 17 years
What is being tested?
Cefiderocol
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
23 sitesin 9 countries
Study dates
21 Aug 2020to 6 Feb 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 months to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 16Show fewer
  • 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.
  • Participant is receiving vasopressor therapy at Screening.

Trial locations and contacts

23 sites in 9 countries.

23 sites in 9 countries

Thailand4 sites
  • King Chulalongkorn Memorial Hospital, Chulalongkorn University

    Bangkok

  • Siriraj Hospital

    Bangkok Noi

  • PHPT-Chiangrai PrachanuKroh Hospital

    Chiang Mai

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

    Khon Kaen

Other trials in Thailand

Ukraine4 sites
  • Dnipropetrovsk Regional Children Clinical Hospital

    Kharkiv

  • Regional Children Clinical Hospital

    Kharkiv

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

    Kiev

  • Higher State Educational Institute of Ukraine Ukrainian Medical Stamatological Academy

    Poltava

Other trials in Ukraine

Georgia3 sites
  • JSC "Medical Corporation Evex" " M. Iashvili Batumi Maternal and Child Central Hospital"

    Batumi

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

    Tbilisi

  • Ltd Unimedi Kakheti Childrens New Clinic

    Tbilisi

Other trials in Georgia

Belgium2 sites
  • Universitair Ziekenhuis Brussel

    Brussels, 1200

  • Cliniques Universitaires Saint-Luc

    Brussels

Other trials in Belgium

Estonia2 sites
  • Tallinn Childrens Hospital

    Tallinn

  • Tartu Ulikooli Kliinikum - Anestesioloogia ja Intensiivravi Kliinik

    Tartu

Other trials in Estonia

Hungary2 sites
  • Heim Pl Orszgos Gyermekgygyszati Intzet

    Pilisborosjenő

  • Szegedi Tudomnyegyetem

    Szegedi Tudomnyegyetem

Other trials in Hungary

Latvia2 sites
  • Daugavpils regional Hospital

    Daugavpils

  • Bernu Kliniska Universitates Slimnica Childrens Hospital - Tornakalna

    Riga

Other trials in Latvia

Russia2 sites
  • St. Petersburg State Pediatric Medical University

    Saint Petersburg

  • Smolensk State Medical University

    Smolensk

Other trials in Russia

Spain2 sites
  • Hospital Germans Trias i Pujol

    Barcelona

  • Hospital Universitario y Politecnico La Fe

    Valencia

Other trials in Spain

About this study

Official title: 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
Read the 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.

Being tested
Cefiderocol, Standard of Care
Medical subject headings
Gram-Negative Bacterial Infections, Sepsis, Healthcare-Associated Pneumonia, Pneumonia, Ventilator-Associated

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CefiderocolDrug

    Also called S-649266, Fetroja

    Administered intravenously over 3 hours

  • Standard of CareDrug

    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.

Study groups in NCT04335539
Study groupRoleWhat they receive
Single Dose Phase: CefiderocolExperimentalParticipants 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.
Receives: Drug: Cefiderocol; Drug: Standard of Care
Multiple Dose Phase: CefiderocolExperimentalParticipants 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.
Receives: Drug: Cefiderocol; Drug: Standard of Care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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'.

    Measured: Day 1 up to Day 28

  2. 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'.

    Measured: Day 1 up to Day 42

  3. Single Dose Phase: Maximum Observed Plasma Concentration (Cmax) of Cefiderocol

    Measured: Up to 8 hours postdose

  4. Single Dose Phase: Area Under the Plasma Concentration Time Curve Extrapolated From Time 0 to Infinity (AUCinf) of Cefiderocol

    Measured: Up to 8 hours postdose

  5. Single Dose Phase: Apparent Terminal Elimination Half-life (t1/2) of Cefiderocol

    Measured: Up to 8 hours postdose

  6. Multiple Dose Phase: Cmax of Cefiderocol

    Measured: Up to 8 hours postdose

  7. Multiple Dose Phase: Area Under the Plasma Concentration Time Curve Extrapolated From Time 0 to the Last Measurable Concentration (AUC0-t) of Cefiderocol

    Measured: Up to 8 hours postdose

  8. Multiple Dose Phase: t1/2 of Cefiderocol

    Measured: Up to 8 hours postdose

Secondary outcomes (2)
  1. 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.

    Measured: 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])

  2. 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.

    Measured: 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])

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Apr 2020
  2. Study start21 Aug 2020
  3. Primary completion6 Feb 2023
  4. Study completion6 Feb 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04335539
Sponsor's protocol ID
1802R2135
Other IDs
2019-002120-32, 2019
Status last verified
Feb 2026
First submitted
3 Apr 2020
Last updated
27 Feb 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

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.

    PubMed 39230271

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cefiderocol in people with Gram-negative Bacterial Infections and Bloodstream Infections (BSI), run by Shionogi at 23 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Thailand, Ukraine, Georgia, Belgium, Estonia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Single-Dose Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: Day 1 up to Day 28). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04335539, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2026.

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