Gram-negative Bacterial InfectionsPhase 2NCT04215991
A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Cefiderocol in Hospitalized Pediatric Participants
A Phase 2 study testing Cefiderocol in people with Gram-negative Bacterial Infections and Hospital Acquired Bacterial Pneumonia (HABP), run by Shionogi at 25 sites in 10 countries.
Trial summary
The primary objectives of this study are to assess the safety, tolerability, and pharmacokinetics (PK) of cefiderocol after single-dose administration in hospitalized pediatric participants 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections and after multiple-dose… Read more about this study
- Who is it for?
- Ages 3 months to 17 years
- Conditions the study is for
- Gram-negative Bacterial Infections, Hospital Acquired Bacterial Pneumonia (HABP), Complicated Urinary Tract Infection (cUTI)
- 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
- 91 participants
- Where
- 25 sitesin 10 countries
- Study dates
- 19 Feb 2020to 17 Sep 2024
- Phase
- Phase 2
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(s) (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 board/independent ethics committee [IRBs/IECs] 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 multiple-dose phase. Hospitalized participant is 3 months to < 12 years of age at the time written informed consent/assent is obtained for the single-dose phase.
- Single-dose phase: Participant has a suspected or confirmed infection type (including but not limited to cUTI, complicated intra-abdominal infections [cIAI], pneumonia, HABP/VABP, and sepsis or bloodstream infections [BSI]) that requires hospitalization for treatment with IV antibiotics.
- Multiple-dose phase: Participant has a suspected or confirmed cUTI, HABP, or VABP 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 (for example, 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 the 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)/ minute (min)/1.73 square meters (m^2)² at Screening .
- Multiple-dose phase: Participant has an eGFR (based on the 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 m² 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 with 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
25 sites in 10 countries.
25 sites in 10 countries
Greece5 sites
University Hospital "ATTIKON" 3rd Pediatric Clinic of NKUA
Chaïdári, 12462
Heraklion University General Hospital
Heraklion, Crete, 7110
University General Hospital of Larissa
Larissa, Thessaly, 41110
Hippokration Hospital 3rd Pediatric Clinic of AUTH Konstantinoupoleos 49
Thessaloniki, 54642
General Hospital of Thessaloniki Papageorgiou
Thessaloniki, 56403
Lithuania3 sites
Hospital of Lithuanian University of Health Sciences Kauno klinikos
Kaunas, LT-50161
Klaipeda Children's Hospital
Klaipėda, LT-92140
Vilnius University Hospital Santaros Klinikos
Vilnius, LT-08406
Philippines3 sites
Chong Hua Hospital
Cebu City, 6000
Western Visayas and Medical Center
Iloilo City, 5000
Manila Doctor's Hospital
Manila, 1000
Ukraine3 sites
Municipal Noncommercial Enterprise of Kharkiv Regional Council " V.I.Shapoval Regional Clinical Center of Urology and Nephrology", Department of Children Urology # 7
Kharkiv, 61037
Vinnytsia Regional Children's Hospital
Vinnytsia, 21000
Zaporizhzhia Regional Children Clinical Hospital
Zaporizhzhya, 69063
United States2 sites
Cook Children's Medical Center
Fort Worth, Texas, 76104
University of Iowa Stead Family Children's Hospital
Iowa City, Iowa, 52242
Georgia2 sites
JSC "EVEX Medical Corporation"- M Lashvili Childrens Central Hospital
Tbilisi, 0159
Ltd Unimedi Kakheti Childrens New Clinic
Tbilisi, 0159
Mexico2 sites
Hospital Civil de Guadalajara Hospital 278, El retiro, Torre Piso 10, Infectología Ped.
Guadalajara, Jalisco, 44280
Instituto Nacional de Pediatría "Laboratorio de la Unidad de Apoyo a la Investigación Clínica", Planta Baja Col. Insurgentes Cuicuilco, Delegacion Coyoacán Av. Insurgentes Sur 3700-C
Mexico City, 4530
Panama2 sites
Hospital de Especialidades Ped Via España y Calle Zarak
Panama City, 0801
Hospital del Niño, Epidemiologia
Panama City, 0816-00383
Spain2 sites
Hospital Val d'Hebron
Barcelona, 08035
Hospital del Mar, Passeig Marítim 25-29
Barcelona, 8003
Australia1 site
Queensland Children's Health Precinct Level 8, Centre for Children's Health Research 62 Graham Street
South Brisbane, Queensland, 4101
About this study
Official title: An Open-label Study With a Nonrandomized Single-dose Phase in Subjects With Suspected or Confirmed Aerobic Gram-negative Bacterial Infections Followed by a Randomized, Multiple-dose, Active-controlled Phase in Subjects With Suspected or Confirmed Complicated Urinary Tract Infection (cUTI), Hospital-acquired Bacterial Pneumonia (HABP) or Ventilator-associated Bacterial Pneumonia (VABP) to Assess the Safety, Tolerability, and Pharmacokinetics of Cefiderocol in Hospitalized Pediatric Subjects 3 Months to < 18 Years of Age
The primary objectives of this study are to assess the safety, tolerability, and pharmacokinetics (PK) of cefiderocol after single-dose administration in hospitalized pediatric participants 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections and after multiple-dose administration in hospitalized pediatric participants 3 months to < 18 years of age with suspected or confirmed complicated urinary tract infection (cUTI), hospital-acquired bacterial pneumonia (HABP), or ventilator-associated bacterial pneumonia (VABP).
Read the detailed description
This study consists of a nonrandomized single-dose phase in children aged 3 months to less than 12 years with suspected or confirmed aerobic Gram-negative bacterial infections and a randomized multiple-dose, active-comparator standard of care (SOC) phase in children aged 3 months to less than 18 years with cUTI, HABP, or VABP to assess the PK, safety, and tolerability of cefiderocol in hospitalized participants requiring systemic antibiotics for an expected 5 to 14 days.
- Conditions
- Gram-negative Bacterial Infections, Hospital Acquired Bacterial Pneumonia (HABP), Complicated Urinary Tract Infection (cUTI), Ventilator Associated Bacterial Pneumonia (VABP)
- Being tested
- Cefiderocol, Standard of Care
- Medical subject headings
- Gram-Negative Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CefiderocolDrug
Also called Fetroja, S-649266
Administered intravenously over 3 hours
Standard of CareDrug
Standard of care administered will be selected by the investigator based on the suspected or confirmed pathogen(s) for the infection in accordance with local standards.
| Study group | Role | What they receive |
|---|---|---|
| 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 cefiderocol and participants ≥34 kg will receive 2000 mg. Receives: Drug: Cefiderocol; Drug: Standard of Care |
| Multiple Dose Phase: Cefiderocol | Experimental | Participants will receive cefiderocol administered via IV every 8 hours for an expected 5 to 14 days in addition to standard of care. Participants weighing less than 34 kg will receive 60 mg/kg cefiderocol and participants ≥ 34 kg will receive 2000 mg. Dosage may be adjusted based on renal function. Receives: Drug: Cefiderocol; Drug: Standard of Care |
| Multiple Dose Phase: Standard of Care Alone | Active comparator | Participants will receive standard of care treatment according to local standards. Receives: Drug: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events in the Single Dose Phase
Measured: 28 days
Maximum Observed Plasma Concentration (Cmax) of Cefiderocol in the Single Dose Phase
Measured: Day 1, 1 (cohort 2 only), 3, 3.5 (cohort 2 only), 5, and 8 hours after the start of infusion
Area Under the Plasma Concentration Time Curve Extrapolated from Time 0 to Infinity (AUCinf) of Cefiderocol in the Single Dose Phase
Measured: Day 1, 1 (cohort 2 only), 3, 3.5 (cohort 2 only), 5, and 8 hours after the start of infusion
Apparent Terminal Elimination Half-life of Cefiderocol in the Single Dose Phase
Measured: Day 1, 1 (cohort 2 only), 3, 3.5 (cohort 2 only), 5, and 8 hours after the start of infusion
Number of Participants with Adverse Events in the Multiple Dose Phase
Measured: Up to 28 days after last dose (33 to 42 days depending on treatment duration)
Maximum Observed Plasma Concentration of Cefiderocol in the Multiple Dose Phase
Measured: During one of the dosing intervals from Day 5-14, 1 (cohort 2 1 and 2 only), 3, 3.5 (cohorts 1 and 2 only), 5, and 8 hours after the start of infusion
Area Under the Plasma Concentration Time Curve Over the Dosing Interval τ (AUC0-τ) of Cefiderocol in the Multiple Dose Phase
Measured: During one of the dosing intervals from Day 5-14, 1 (cohort 2 1 and 2 only), 3, 3.5 (cohorts 1 and 2 only), 5, and 8 hours after the start of infusion
Apparent Terminal Elimination Half-life of Cefiderocol in the Multiple Dose Phase
Measured: During one of the dosing intervals from Day 5-14, 1 (cohort 2 1 and 2 only), 3, 3.5 (cohorts 1 and 2 only), 5, and 8 hours after the start of infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2020
- Study start19 Feb 2020
- Primary completion17 Sep 2024
- Study completion17 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gram-negative Bacterial InfectionsStudies of the same condition, open and under way.
- More trials run by ShionogiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shionogi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shionogi Clinical Trials Administrator Clinical Support Help Line, Study director, Shionogi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04215991
- Sponsor's protocol ID
- 1704R2133
- Other IDs
- 2019-002121-30, 2019
- Status last verified
- May 2025
- First submitted
- 29 Dec 2019
- Last updated
- 25 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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