A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Cefiderocol in Hospitalized Neonates and Infants

Gram-Negative Bacterial Infections Clinical Trial

Official title:

A Multicenter, Single-arm, Open-label Study to Assess the Pharmacokinetics, Safety, and Tolerability of Cefiderocol in Hospitalized Pediatric Patients From Birth to < 3 Months of Age With Suspected or Confirmed Aerobic Gram-negative Bacterial Infections

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06086626
• Other study ID #: 1904R2136
• Status: Recruiting
• Phase: Phase 2
• Start date: March 14, 2024
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2024
• Source: Shionogi Inc.
• Contact: Shionogi Clinical Trials Administrator Clinical Support Help Lin
• Phone: 1-800-849-9707
• Email: Shionogiclintrials-admin[@]shionogi.co.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to understand the pharmacokinetics (PK) of single and multiple doses of cefiderocol in children from birth to less than 3 months of age with suspected or confirmed aerobic Gram-negative bacterial infections.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 3 Months

Eligibility

Eligibility Criteria: Key Inclusion Criteria:

1. Written informed consent has been provided by parent(s) or legally authorized representative(s) in accordance with local regulatory requirements

2. Hospitalized infants from birth to < 3 months (< 90 days) of age at the time written informed consent is provided. Enrollment of premature infants will not be restricted, but they must have a GA = 26 weeks, PNA of 0 to 3 months, and weight of at least 1 kilogram (kg)

3. Require systemic IV antibiotic treatment for suspected or confirmed aerobic Gram-negative infections including, but not limited to, complicated urinary tract infection, complicated intra-abdominal infection, hospital-acquired/ ventilator-associated bacterial pneumonia, and BSI/sepsis

4. For the multiple-dose phase, within 72 hours of the start of potentially effective treatment with SOC antibiotics for the suspected or confirmed primary aerobic Gram-negative infection

Key Exclusion Criteria:

1. Documented history of any moderate or severe hypersensitivity or allergic reaction to any ß-lactam antibiotic

2. Life expectancy of < 72 hours after enrollment

3. Urine output < 1.0 milliliter (mL)/kg/hour within the 24 hours prior to study drug administration on Day 1

4. Serum creatinine value greater than the maximum for GA and PNA shown below within the 24 hours prior to study drug administration on Day 1

5. Neonatal acute kidney injury (AKI), defined as a serum creatinine level greater than 1.5 milligrams per decilieter (mg/dL) (133 micromoles[µmol]/liter [L]) or an increase of 0.3 mg/dL (17 to 27 µmol/L) per day from a previous lower value

6. Acute kidney injury based on an increase in serum creatinine = 0.3 mg/dL within 48 hours from an established baseline value

7. 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

8. Receiving renal replacement therapy

9. Received any other investigational medicinal product within 30 days of study drug administration

10. Receiving treatment with a vasopressor at Screening

11. Has a confirmed or strongly suspected infection at Screening with a pathogen known to be resistant to cefiderocol or only a Gram-positive pathogen or viral, fungal, or parasitic pathogen as the sole cause of infection

12. Anticipated need for antibacterial therapy longer than 14 days (example , osteomyelitis or endocarditis); this applies to both study treatment with cefiderocol, as well as adjunctive IV antibacterial treatment for suspected coinfection with Gram-positive organisms or multidrug resistant Gram-negative organisms

13. Suspected or confirmed central nervous system (CNS) infection, including suspected CNS infection who do not have a lumbar puncture (LP) but who are treated for potential CNS infection, evidence suggestive of CNS infection based on LP results (polymorphonuclear pleocytosis, hypoglycorrhachia, and increased protein concentration), regardless of culture results, LP with organisms on Gram stain or culture-positive cerebrospinal fluid

Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Bacterial Infections
• Communicable Diseases
• Gram-Negative Bacterial Infections
• Infections

Intervention

Drug:
• Cefiderocol
Administered via intravenous (IV) infusion
• Standard of Care
Antibiotics selected by the investigator based on the participant's symptoms, in accordance with local standards

Locations

Country	Name	City	State
South Africa	Tygerberg Hospital	Cape Town	Western Cape
Taiwan	Chang Gung Memorial Hospital, Linkou Department of Pediatrics	Taoyuan City
United States	Duke University	Durham	North Carolina
United States	Arkansas Children's Hospital	Little Rock	Arkansas

Sponsors (1)

Lead Sponsor	Collaborator
Shionogi

Countries where clinical trial is conducted

United States,  South Africa,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) After a Single Dose of Cefiderocol		Up to 8 hours postdose
Primary	Cmax After a Minimum of 4 Doses of Cefiderocol		Up to 8 hours postdose
Primary	Area Under the Concentration-Time Curve Extrapolated From Time 0 to Infinity (AUC0-inf) After Single Dose of Cefiderocol		Up to 8 hours postdose
Primary	Area Under the Concentration-Time Curve Over the Dosing Interval (AUC0-†) After a Minimum of 4 Doses of Cefiderocol		Up to 3 hours
Primary	Terminal Elimination Half-Life (t1/2) After a Single Dose of Cefiderocol		Up to 8 hours postdose
Primary	Terminal Elimination Half-Life (t1/2) After a Minimum of 4 Doses of Cefiderocol		Up to 8 hours postdose
Secondary	Number of Participants With Adverse Events (AEs)		Up to 28 days