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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04215991




Registration number
NCT04215991
Ethics application status
Date submitted
29/12/2019
Date registered
2/01/2020
Date last updated
5/06/2024

Titles & IDs
Public title
A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Cefiderocol in Hospitalized Pediatric Participants
Scientific 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
Secondary ID [1] 0 0
2019-002121-30
Secondary ID [2] 0 0
1704R2133
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gram-negative Bacterial Infections 0 0
Hospital Acquired Bacterial Pneumonia (HABP) 0 0
Complicated Urinary Tract Infection (cUTI) 0 0
Ventilator Associated Bacterial Pneumonia (VABP) 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cefiderocol
Treatment: Drugs - Standard of Care

Experimental: 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.

Experimental: 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.

Active Comparator: Multiple Dose Phase: Standard of Care Alone - Participants will receive standard of care treatment according to local standards.


Treatment: Drugs: Cefiderocol
Administered intravenously over 3 hours

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Adverse Events in the Single Dose Phase
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
Maximum Observed Plasma Concentration (Cmax) of Cefiderocol in the Single Dose Phase
Timepoint [2] 0 0
Day 1, 1 (cohort 2 only), 3, 3.5 (cohort 2 only), 5, and 8 hours after the start of infusion
Primary outcome [3] 0 0
Area Under the Plasma Concentration Time Curve Extrapolated from Time 0 to Infinity (AUCinf) of Cefiderocol in the Single Dose Phase
Timepoint [3] 0 0
Day 1, 1 (cohort 2 only), 3, 3.5 (cohort 2 only), 5, and 8 hours after the start of infusion
Primary outcome [4] 0 0
Apparent Terminal Elimination Half-life of Cefiderocol in the Single Dose Phase
Timepoint [4] 0 0
Day 1, 1 (cohort 2 only), 3, 3.5 (cohort 2 only), 5, and 8 hours after the start of infusion
Primary outcome [5] 0 0
Number of Participants with Adverse Events in the Multiple Dose Phase
Timepoint [5] 0 0
Up to 28 days after last dose (33 to 42 days depending on treatment duration)
Primary outcome [6] 0 0
Maximum Observed Plasma Concentration of Cefiderocol in the Multiple Dose Phase
Timepoint [6] 0 0
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
Primary outcome [7] 0 0
Area Under the Plasma Concentration Time Curve Over the Dosing Interval t (AUC0-t) of Cefiderocol in the Multiple Dose Phase
Timepoint [7] 0 0
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
Primary outcome [8] 0 0
Apparent Terminal Elimination Half-life of Cefiderocol in the Multiple Dose Phase
Timepoint [8] 0 0
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

Eligibility
Key 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.
Minimum age
3 Months
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 (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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/02/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2024
Actual
Sample size
Target
85
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Queensland Children's Health Precinct Level 8, Centre for Children's Health Research 62 Graham Street - South Brisbane
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Texas
Country [2] 0 0
Greece
State/province [2] 0 0
Crete
Country [3] 0 0
Greece
State/province [3] 0 0
Thessaly
Country [4] 0 0
Greece
State/province [4] 0 0
Chaidari
Country [5] 0 0
Greece
State/province [5] 0 0
Thessaloniki
Country [6] 0 0
Lithuania
State/province [6] 0 0
Kaunas
Country [7] 0 0
Lithuania
State/province [7] 0 0
Klaipeda
Country [8] 0 0
Lithuania
State/province [8] 0 0
Vilnius
Country [9] 0 0
Mexico
State/province [9] 0 0
Jalisco
Country [10] 0 0
Mexico
State/province [10] 0 0
Ciudad de México
Country [11] 0 0
Panama
State/province [11] 0 0
Ciudad de Panama
Country [12] 0 0
Panama
State/province [12] 0 0
Panama City
Country [13] 0 0
Philippines
State/province [13] 0 0
Cebu City
Country [14] 0 0
Philippines
State/province [14] 0 0
Iloilo City
Country [15] 0 0
Philippines
State/province [15] 0 0
Manila
Country [16] 0 0
Spain
State/province [16] 0 0
Barcelona
Country [17] 0 0
Ukraine
State/province [17] 0 0
Kharkiv
Country [18] 0 0
Ukraine
State/province [18] 0 0
Vinnytsia
Country [19] 0 0
Ukraine
State/province [19] 0 0
Zaporizhzhia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Shionogi
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT04215991
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Shionogi Clinical Trials Administrator Clinical Support Help Line
Address 0 0
Shionogi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Shionogi Clinical Trials Administrator Clinical Support Help Line
Address 0 0
Country 0 0
Phone 0 0
800-849-9707
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04215991