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

Gram-negative Bacterial Infections Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04215991
• Other study ID #: 1704R2133
• Secondary ID: 2019-002121-30
• Status: Recruiting
• Phase: Phase 2
• Start date: February 19, 2020
• Est. completion date: September 30, 2024

Study information

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

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 85
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• 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(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 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.

Related Conditions & MeSH terms

• Bacterial Infections
• Communicable Diseases
• Complicated Urinary Tract Infection (cUTI)
• Gram-negative Bacterial Infections
• Infections
• Pneumonia
• Pneumonia, Bacterial
• Urinary Tract Infections

Intervention

Drug:
• Cefiderocol
Administered intravenously over 3 hours
• 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.

Locations

Country	Name	City	State
Australia	Queensland Children's Health Precinct Level 8, Centre for Children's Health Research 62 Graham Street	South Brisbane	Queensland
Greece	University Hospital "ATTIKON" 3rd Pediatric Clinic of NKUA	Chaidari
Greece	Heraklion University General Hospital	Heraklion	Crete
Greece	University General Hospital of Larissa	Larissa	Thessaly
Greece	General Hospital of Thessaloniki Papageorgiou	Thessaloniki
Greece	Hippokration Hospital 3rd Pediatric Clinic of AUTH Konstantinoupoleos 49	Thessaloniki
Lithuania	Hospital of Lithuanian University of Health Sciences Kauno klinikos	Kaunas
Lithuania	Klaipeda Children's Hospital	Klaipeda
Lithuania	Vilnius University Hospital Santaros Klinikos	Vilnius
Mexico	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	Hospital Civil de Guadalajara Hospital 278, El retiro, Torre Piso 10, Infectología Ped.	Guadalajara	Jalisco
Panama	Hospital de Especialidades Ped Via España y Calle Zarak	Ciudad de Panama
Panama	Hospital del Niño, Epidemiologia	Panama City
Philippines	Chong Hua Hospital	Cebu City
Philippines	Western Visayas and Medical Center	Iloilo City
Philippines	Manila Doctor's Hospital	Manila
Spain	Hospital del Mar, Passeig Marítim 25-29	Barcelona
Spain	Hospital Val d'Hebron	Barcelona
Ukraine	Municipal Noncommercial Enterprise of Kharkiv Regional Council " V.I.Shapoval Regional Clinical Center of Urology and Nephrology", Department of Children Urology # 7	Kharkiv
Ukraine	Vinnytsia Regional Children's Hospital	Vinnytsia
Ukraine	Zaporizhzhia Regional Children Clinical Hospital	Zaporizhzhia
United States	Cook Children's Medical Center	Fort Worth	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Shionogi

Countries where clinical trial is conducted

United States,  Australia,  Greece,  Lithuania,  Mexico,  Panama,  Philippines,  Spain,  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		Day 1, 1 (cohort 2 only), 3, 3.5 (cohort 2 only), 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		Day 1, 1 (cohort 2 only), 3, 3.5 (cohort 2 only), 5, and 8 hours after the start of infusion
Primary	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
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 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
Primary	Area Under the Plasma Concentration Time Curve Over the Dosing Interval t (AUC0-t) 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
Primary	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