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

Sepsis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04335539
• Other study ID #: 1802R2135
• Secondary ID: 2019-002120-32
• Status: Completed
• Phase: Phase 2
• Start date: August 21, 2020
• Est. completion date: February 6, 2023

Study information

• Verified date: January 2024
• Source: Shionogi Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: February 6, 2023
• Est. primary completion date: February 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 17 Years

Eligibility

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 ß-lactam antibiotic (Note: for ß-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.

Related Conditions & MeSH terms

• Bacterial Infections
• Bloodstream Infections (BSI)
• Communicable Diseases
• Complicated Intra-abdominal Infection (cIAI)
• Complicated Urinary Tract Infection (cUTI)
• Gram-negative Bacterial Infections
• Healthcare-Associated Pneumonia
• Hospital Acquired Pneumonia (HAP)
• Infections
• Intraabdominal Infections
• Pneumonia
• Pneumonia, Ventilator-Associated
• Sepsis
• Urinary Tract Infections
• Ventilator-acquired Pneumonia

Intervention

Drug:
• Cefiderocol
Administered intravenously over 3 hours
• 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.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Universitair Ziekenhuis Brussel	Brussels
Estonia	Tallinn Childrens Hospital	Tallin
Estonia	Tartu Ulikooli Kliinikum - Anestesioloogia ja Intensiivravi Kliinik	Tartu
Georgia	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
Hungary	Heim Pl Orszgos Gyermekgygyszati Intzet	Pilisborosjeno
Hungary	Szegedi Tudomnyegyetem	Szegedi Tudomnyegyetem
Latvia	Daugavpils regional Hospital	Daugavpils
Latvia	Bernu Kliniska Universitates Slimnica Childrens Hospital - Tornakalna	Riga
Russian Federation	Smolensk State Medical University	Smolensk
Russian Federation	St. Petersburg State Pediatric Medical University	St. Petersburg
Spain	Hospital Germans Trias i Pujol	Barcelona
Spain	Hospital Universitario y Politecnico La Fe	Valencia
Thailand	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
Ukraine	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

Sponsors (1)

Lead Sponsor	Collaborator
Shionogi

Countries where clinical trial is conducted

Belgium,  Estonia,  Georgia,  Hungary,  Latvia,  Russian Federation,  Spain,  Thailand,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events in the Single Dose Phase		28 days
Primary	Maximum Observed Plasma Concentration (Cmax) of Cefiderocol in the Single Dose Phase		Cohorts 1 and 2: Day 1 at 1, 3, 3.5, 5, and 8 hours after start of infusion. Cohorts 3 and 4: Day 1 at 3, 5, and 8 hours after the start of infusion.
Primary	Area Under the Plasma Concentration Time Curve Extrapolated From Time 0 to Infinity (AUCinf) of Cefiderocol in the Single Dose Phase		Cohorts 1 and 2: Day 1 at 1, 3, 3.5, 5, and 8 hours after start of infusion. Cohorts 3 and 4: Day 1 at 3, 5, and 8 hours after the start of infusion.
Primary	Apparent Terminal Elimination Half-life of Cefiderocol in the Single Dose Phase		Cohorts 1 and 2: Day 1 at 1, 3, 3.5, 5, and 8 hours after start of infusion. Cohorts 3 and 4: Day 1 at 3, 5, and 8 hours after the start of infusion.
Primary	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)
Primary	Maximum Observed Plasma Concentration (Cmax) of Cefiderocol in the Multiple Dose Phase		During one of the dosing intervals from the 6th to the 12th dose of cefiderocol: Cohort 2: at 1, 3, 3.5, 5, and 8 hours after start of infusion. Cohorts 3 and 4: at 3, 5, and 8 hours after start of infusion.
Primary	Area Under the Plasma Concentration Time Curve Extrapolated From Time 0 to Infinity (AUCinf) of Cefiderocol in the Multiple Dose Phase		During one of the dosing intervals from the 6th to the 12th dose of cefiderocol: Cohort 2: at 1, 3, 3.5, 5, and 8 hours after start of infusion. Cohorts 3 and 4: at 3, 5, and 8 hours after start of infusion.
Primary	Apparent Terminal Elimination Half-life of Cefiderocol in the Multiple Dose Phase		During one of the dosing intervals from the 6th to the 12th dose of cefiderocol: Cohort 2: at 1, 3, 3.5, 5, and 8 hours after start of infusion. Cohorts 3 and 4: at 3, 5, and 8 hours after start of infusion.
Secondary	Percentage of Participants with a Clinical Response in the Multiple Dose Phase		At 7 and 28 days after the end of treatment
Secondary	Percentage of Participants with a Microbiological Response Per Pathogen in the Multiple Dose Phase		At 7 and 28 days after the end of treatment