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

NCT ID: NCT04215991

Last Updated: 2025-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-19
• Study Completion Date: 2024-09-17

Brief 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 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).

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)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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 cefiderocol and participants ≥34 kg will receive 2000 mg.

Group Type: EXPERIMENTAL

Cefiderocol

Intervention Type: DRUG

Administered intravenously over 3 hours

Standard of Care

Intervention Type: DRUG

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.

Multiple Dose Phase: Cefiderocol

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.

Group Type: EXPERIMENTAL

Cefiderocol

Intervention Type: DRUG

Administered intravenously over 3 hours

Standard of Care

Intervention Type: DRUG

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.

Multiple Dose Phase: Standard of Care Alone

Participants will receive standard of care treatment according to local standards.

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: DRUG

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.

Interventions

Cefiderocol

Administered intravenously over 3 hours

Intervention Type: DRUG

Standard of Care

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.

Intervention Type: DRUG

Other Intervention Names

Fetroja; S-649266

Eligibility Criteria

Inclusion Criteria

1. Participant's parent(s) or legally authorized representative(s) (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 board/independent ethics committee [IRBs/IECs] 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 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.

4. 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

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 (for example, 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 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.

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 with 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.

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shionogi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shionogi Clinical Trials Administrator Clinical Support Help Line

Role: STUDY_DIRECTOR

Shionogi

Locations

University of Iowa Stead Family Children's Hospital

Iowa City, Iowa, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Queensland Children's Health Precinct Level 8, Centre for Children's Health Research 62 Graham Street

South Brisbane, Queensland, Australia

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

Tbilisi, , Georgia

Ltd Unimedi Kakheti Childrens New Clinic

Tbilisi, , Georgia

Heraklion University General Hospital

Heraklion, Crete, Greece

University General Hospital of Larissa

Larissa, Thessaly, Greece

University Hospital "ATTIKON" 3rd Pediatric Clinic of NKUA

Chaïdári, , Greece

Hippokration Hospital 3rd Pediatric Clinic of AUTH Konstantinoupoleos 49

Thessaloniki, , Greece

General Hospital of Thessaloniki Papageorgiou

Thessaloniki, , Greece

Hospital of Lithuanian University of Health Sciences Kauno klinikos

Kaunas, , Lithuania

Klaipeda Children's Hospital

Klaipėda, , Lithuania

Vilnius University Hospital Santaros Klinikos

Vilnius, , Lithuania

Hospital Civil de Guadalajara Hospital 278, El retiro, Torre Piso 10, Infectología Ped.

Guadalajara, Jalisco, Mexico

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, , Mexico

Hospital de Especialidades Ped Via España y Calle Zarak

Panama City, , Panama

Hospital del Niño, Epidemiologia

Panama City, , Panama

Chong Hua Hospital

Cebu City, , Philippines

Western Visayas and Medical Center

Iloilo City, , Philippines

Manila Doctor's Hospital

Manila, , Philippines

Hospital Val d'Hebron

Barcelona, , Spain

Hospital del Mar, Passeig Marítim 25-29

Barcelona, , Spain

Municipal Noncommercial Enterprise of Kharkiv Regional Council " V.I.Shapoval Regional Clinical Center of Urology and Nephrology", Department of Children Urology # 7

Kharkiv, , Ukraine

Vinnytsia Regional Children's Hospital

Vinnytsia, , Ukraine

Zaporizhzhia Regional Children Clinical Hospital

Zaporizhzhia, , Ukraine

Countries

United States; Australia; Georgia; Greece; Lithuania; Mexico; Panama; Philippines; Spain; Ukraine

References

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.

Reference Type: DERIVED

PMID: 39230271 (View on PubMed)

Other Identifiers

2019-002121-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1704R2133

Identifier Type: -

Identifier Source: org_study_id