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

NCT04215991 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 1704R21332019-002121-30
• Study Type: interventional
• Target: 91
• Locations: 10 countries
• Sites: 25

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).

Conditions

Gram-negative Bacterial Infections; Hospital Acquired Bacterial Pneumonia (HABP); Complicated Urinary Tract Infection (cUTI); Ventilator Associated Bacterial Pneumonia (VABP)

Outcome Measures

Primary Outcomes (8)

• Number of Participants with Adverse Events in the Single Dose Phase

  28 days

• Maximum Observed Plasma Concentration (Cmax) of Cefiderocol in the Single Dose Phase

  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

  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

  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

  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

  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

  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

  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

Study Arms (3)

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.

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.

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.

Drug: Standard of Care

Interventions

Cefiderocol DRUG

Administered intravenously over 3 hours

Also known as: Fetroja, S-649266

Multiple Dose Phase: Cefiderocol; Single Dose Phase: Cefiderocol

Standard of Care 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; Multiple Dose Phase: Standard of Care Alone; 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(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.

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 (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.
• 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.

Sponsors & Collaborators

• Shionogi: lead

Study Sites (25)

University of Iowa Stead Family Children's Hospital

Iowa City, Iowa, 52242, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

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

South Brisbane, Queensland, 4101, Australia

Location

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

Tbilisi, 0159, Georgia

Location

Ltd Unimedi Kakheti Childrens New Clinic

Tbilisi, 0159, Georgia

Location

Heraklion University General Hospital

Heraklion, Crete, 7110, Greece

Location

University General Hospital of Larissa

Larissa, Thessaly, 41110, Greece

Location

University Hospital "ATTIKON" 3rd Pediatric Clinic of NKUA

Chaïdári, 12462, Greece

Location

Hippokration Hospital 3rd Pediatric Clinic of AUTH Konstantinoupoleos 49

Thessaloniki, 54642, Greece

Location

General Hospital of Thessaloniki Papageorgiou

Thessaloniki, 56403, Greece

Location

Hospital of Lithuanian University of Health Sciences Kauno klinikos

Kaunas, LT-50161, Lithuania

Location

Klaipeda Children's Hospital

Klaipėda, LT-92140, Lithuania

Location

Vilnius University Hospital Santaros Klinikos

Vilnius, LT-08406, Lithuania

Location

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

Guadalajara, Jalisco, 44280, Mexico

Location

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, Mexico

Location

Hospital de Especialidades Ped Via España y Calle Zarak

Panama City, 0801, Panama

Location

Hospital del Niño, Epidemiologia

Panama City, 0816-00383, Panama

Location

Chong Hua Hospital

Cebu City, 6000, Philippines

Location

Western Visayas and Medical Center

Iloilo City, 5000, Philippines

Location

Manila Doctor's Hospital

Manila, 1000, Philippines

Location

Hospital Val d'Hebron

Barcelona, 08035, Spain

Location

Hospital del Mar, Passeig Marítim 25-29

Barcelona, 8003, Spain

Location

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

Kharkiv, 61037, Ukraine

Location

Vinnytsia Regional Children's Hospital

Vinnytsia, 21000, Ukraine

Location

Zaporizhzhia Regional Children Clinical Hospital

Zaporizhzhia, 69063, 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

Interventions

Cefiderocol; Standard of Care

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections

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

Study Officials

• Shionogi Clinical Trials Administrator Clinical Support Help Line

  Shionogi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2019
• First Posted: January 2, 2020
• Study Start: February 19, 2020
• Primary Completion: September 17, 2024
• Study Completion: September 17, 2024
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

PA (2); GE (2); AU (1); PH (3); LI (3); ME (2); US (2); GR (5); ES (2); UA (3)