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

NCT ID: NCT04335539

Last Updated: 2024-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-21
• Study Completion Date: 2023-02-06

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

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• 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 of 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 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

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.

Group Type: EXPERIMENTAL

Cefiderocol

Intervention Type: DRUG

Administered intravenously over 3 hours

Standard of Care

Intervention Type: 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.

Interventions

Cefiderocol

Administered intravenously over 3 hours

Intervention Type: DRUG

Standard of Care

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.

Intervention Type: DRUG

Other Intervention Names

S-649266; Fetroja

Eligibility Criteria

Inclusion Criteria

1. Participant's parent(s) or legally authorized representative (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 boards/independent ethics committees [IRB's/IEC's] 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 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.

4. 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.

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 (eg, 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 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.

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 has 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

Universitair Ziekenhuis Brussel

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Tallinn Childrens Hospital

Tallinn, , Estonia

Tartu Ulikooli Kliinikum - Anestesioloogia ja Intensiivravi Kliinik

Tartu, , Estonia

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

Batumi, , Georgia

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

Tbilisi, , Georgia

Ltd Unimedi Kakheti Childrens New Clinic

Tbilisi, , Georgia

Heim Pl Orszgos Gyermekgygyszati Intzet

Pilisborosjenő, , Hungary

Szegedi Tudomnyegyetem

Szegedi Tudomnyegyetem, , Hungary

Daugavpils regional Hospital

Daugavpils, , Latvia

Bernu Kliniska Universitates Slimnica Childrens Hospital - Tornakalna

Riga, , Latvia

St. Petersburg State Pediatric Medical University

Saint Petersburg, , Russia

Smolensk State Medical University

Smolensk, , Russia

Hospital Germans Trias i Pujol

Barcelona, , Spain

Hospital Universitario y Politecnico La Fe

Valencia, , Spain

King Chulalongkorn Memorial Hospital, Chulalongkorn University

Bangkok, , Thailand

Siriraj Hospital

Bangkok Noi, , Thailand

PHPT-Chiangrai PrachanuKroh Hospital

Chiang Mai, , Thailand

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

Khon Kaen, , Thailand

Dnipropetrovsk Regional Children Clinical Hospital

Kharkiv, , Ukraine

Regional Children Clinical Hospital

Kharkiv, , Ukraine

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

Kiev, , Ukraine

Higher State Educational Institute of Ukraine Ukrainian Medical Stamatological Academy

Poltava, , Ukraine

Countries

Belgium; Estonia; Georgia; Hungary; Latvia; Russia; Spain; Thailand; 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

2019-002120-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1802R2135

Identifier Type: -

Identifier Source: org_study_id