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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Gram-negative Bacterial Infections; Complicated Urinary Tract Infection (cUTI); Hospital Acquired Bacterial Pneumonia (HABP); Ventilator Associated Bacterial Pneumonia (VABP)
• Intervention / Treatment: Drug: Cefiderocol; Drug: Standard of Care

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 Type: Interventional
• Enrollment (Estimated): 85
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shionogi Clinical Trials Administrator Clinical Support Help Line; Phone Number: 800-849-9707; Email: Shionogiclintrials-admin@shionogi.co.jp

Study Locations

• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Recruiting
      • Queensland Children's Health Precinct Level 8, Centre for Children's Health Research 62 Graham Street
• Greece
  • Chaidari, Greece, 12462
    • Recruiting
    • University Hospital "ATTIKON" 3rd Pediatric Clinic of NKUA
  • Thessaloniki, Greece, 54642
    • Recruiting
    • Hippokration Hospital 3rd Pediatric Clinic of AUTH Konstantinoupoleos 49
  • Thessaloniki, Greece, 56403
    • Recruiting
    • General Hospital Of Thessaloniki Papageorgiou
  • Crete
    • Heraklion, Crete, Greece, 7110
      • Terminated
      • Heraklion University General Hospital
  • Thessaly
    • Larissa, Thessaly, Greece, 41110
      • Recruiting
      • University General Hospital of Larissa
• Lithuania
  • Kaunas, Lithuania, LT-50161
    • Terminated
    • Hospital of Lithuanian University of Health Sciences Kauno klinikos
  • Klaipeda, Lithuania, LT-92140
    • Terminated
    • Klaipeda Children's Hospital
  • Vilnius, Lithuania, LT-08406
    • Recruiting
    • Vilnius University hospital Santaros klinikos
• Mexico
  • Ciudad de México, Mexico, 4530
    • Recruiting
    • 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
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Recruiting
      • Hospital Civil de Guadalajara Hospital 278, El retiro, Torre Piso 10, Infectología Ped.
• Panama
  • Ciudad de Panama, Panama, 0801
    • Terminated
    • Hospital de Especialidades Ped Via España y Calle Zarak
  • Panama City, Panama, 0816-00383
    • Recruiting
    • Hospital del Niño, Epidemiologia
• Philippines
  • Cebu City, Philippines, 6000
    • Recruiting
    • Chong Hua Hospital
  • Iloilo City, Philippines, 5000
    • Recruiting
    • Western Visayas and Medical Center
  • Manila, Philippines, 1000
    • Terminated
    • Manila Doctor's Hospital
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Val d'Hebron
  • Barcelona, Spain, 8003
    • Terminated
    • Hospital del Mar, Passeig Marítim 25-29
• Ukraine
  • Kharkiv, Ukraine, 61037
    • Active, not recruiting
    • Municipal Noncommercial Enterprise of Kharkiv Regional Council " V.I.Shapoval Regional Clinical Center of Urology and Nephrology", Department of Children Urology # 7
  • Vinnytsia, Ukraine, 21000
    • Active, not recruiting
    • Vinnytsia Regional Children's Hospital
  • Zaporizhzhia, Ukraine, 69063
    • Active, not recruiting
    • Zaporizhzhia Regional Children Clinical Hospital
• United States
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Terminated
      • Cook Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

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 (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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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: S-649266; Fetroja; 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: S-649266; Fetroja; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events in the Single Dose Phase	28 days
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 (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
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

Collaborators and Investigators

• Sponsor: Shionogi
• Investigators: Study Director: Shionogi Clinical Trials Administrator Clinical Support Help Line, Shionogi

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2020
• Primary Completion (Estimated): May 15, 2024
• Study Completion (Estimated): June 15, 2024

Study Registration Dates

• First Submitted: December 29, 2019
• First Submitted That Met QC Criteria: December 29, 2019
• First Posted (Actual): January 2, 2020

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Urologic Diseases; Disease Attributes; Bacterial Infections and Mycoses; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Infections; Communicable Diseases; Pneumonia; Urinary Tract Infections; Pneumonia, Bacterial; Bacterial Infections; Gram-Negative Bacterial Infections
• Other Study ID Numbers: 1704R2133; 2019-002121-30 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No