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

Sponsor

Shionogi (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04215991

Collaborator

(none)

Enrollment

Locations

Arms

51.8

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Gram-negative Bacterial Infections Hospital Acquired Bacterial Pneumonia (HABP) Complicated Urinary Tract Infection (cUTI) Ventilator Associated Bacterial Pneumonia (VABP)	Drug: Cefiderocol Drug: Standard of Care	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

85 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official 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

Actual Study Start Date :

Feb 19, 2020

Anticipated Primary Completion Date :

May 15, 2024

Anticipated Study Completion Date :

Jun 15, 2024

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: Cefiderocol Administered intravenously over 3 hours Other Names: Fetroja S-649266 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.
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.	Drug: Cefiderocol Administered intravenously over 3 hours Other Names: Fetroja S-649266 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.
Active Comparator: Multiple Dose Phase: Standard of Care Alone Participants will receive standard of care treatment according to local standards.	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.

Arm

Intervention/Treatment

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.

Drug: Cefiderocol

Administered intravenously over 3 hours

Other Names:

Fetroja

S-649266

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.

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.

Drug: Cefiderocol

Administered intravenously over 3 hours

Other Names:

Fetroja

S-649266

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.

Active Comparator: Multiple Dose Phase: Standard of Care Alone

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

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.

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Months to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.
Participant is receiving vasopressor therapy at Screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
2	Queensland Children's Health Precinct Level 8, Centre for Children's Health Research 62 Graham Street	South Brisbane Queensland		Australia	4101
3	University Hospital "ATTIKON" 3rd Pediatric Clinic of NKUA	Chaidari		Greece	12462
4	Heraklion University General Hospital	Heraklion, Crete		Greece	7110
5	Hippokration Hospital 3rd Pediatric Clinic of AUTH Konstantinoupoleos 49	Thessaloniki		Greece	54642
6	General Hospital of Thessaloniki Papageorgiou	Thessaloniki		Greece	56403
7	Hospital of Lithuanian University of Health Sciences Kauno klinikos	Kaunas		Lithuania	LT-50161
8	Klaipeda Children's Hospital	Klaipeda		Lithuania	LT-92140
9	Vilnius University Hospital Santaros Klinikos	Vilnius		Lithuania	LT-08406
10	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	Ciudad de México		Mexico	4530
11	Hospital Civil de Guadalajara Hospital 278, El retiro, Torre Piso 10, Infectología Ped.	Guadalajara Jalisco		Mexico	44280
12	Hospital de Especialidades Ped Via España y Calle Zarak	Ciudad de Panama		Panama	0801
13	Hosital del Niño, Epidemiologia	Panama City		Panama	0816-00383
14	Chong Hua Hospital	Cebu City		Philippines	6000
15	Western Visayas and Medical Center	Jaro Iloilo City		Philippines	5000
16	Manila Doctors' Hospital	Metro Manila		Philippines	1000
17	Hospital Val d'Hebron	Barcelona		Spain	08035
18	Hospital del Mar, Passeig Marítim 25-29	Barcelona		Spain	8003
19	Municipal Noncommercial Enterprise of Kharkiv Regional Council " V.I.Shapoval Regional Clinical Center of Urology and Nephrology", Department of Children Urology # 7	Kharkiv		Ukraine	61037
20	Vinnytsa Regional Children's Hospital	Vynnytsia		Ukraine	21000
21	Zaporizhzhia Regional Children Chinical Hospital	Zaporizhzhia		Ukraine	69063