Study of cefiderocol or standard of care for paediatric patients with confirmed or suspected Gram-negative bacterial infections receiving a single dose and paediatric patients with confirmed or suspected complicated urinary tract infections receiving multiple doses to assess the safety, tolerability and exposure of cefiderocol.

PHRR200302-002484

1704R2133

2019-CT0519

An Open-label Study with a Non-randomized 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), to Assess the Safety, Tolerability, and Pharmacokinetics of Cefiderocol in Hospitalized Pediatric Subjects 3 Months to < 18 Years of Age

Phase 2, Pediatric ( 3 Months to < 18 Years) 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) to assess the PK, safety, and tolerability of cefiderocol in hospitalized subjects requiring systemic antibiotics for an expected 5 to 14 days.

Ongoing

Complicated Urinary Tract Infection (cUTI)

• To assess the safety and tolerability of cefiderocol after single-dose administration in hospitalized pediatric subjects 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections
• To assess the PK of cefiderocol after single-dose administration in hospitalized pediatric subjects 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections
• To assess the safety and tolerability of cefiderocol after multiple-dose administration in hospitalized pediatric subjects 3 months to < 18 years of age with suspected or confirmed cUTI
• To assess the PK of cefiderocol after multiple-dose administration in hospitalized pediatric subjects 3 months to < 18 years of age with suspected or confirmed cUTI

Multiple-dose phase only: To assess the clinical and microbiological response at the Posttreatment visit (7 [± 4] days following End of Treatment [EOT]) and at the End-of-study [EOS] visit, whenever cefiderocol is administered alone

Pending

• Australia
• Czech Republic
• Greece
• Lithuania
• Mexico
• Panama
• Philippines
• Spain
• Ukraine
• United States

Clinical Trial

20191031102749

2020-01-21

0000-00-00

28

Unspecified

Unspecified

2020-04-30

General Inclusion Criteria
Subjects who fulfill the following criteria will be included in the study.
1. Subject’s parent(s) or legally authorized representative (LAR) provides written informed consent in accordance with regional- and country-specific laws and regulations
2. Subject 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 subject is 3 months to < 18 years of age at the time written informed consent/assent is obtained
4. Single-dose phase: Subject has a suspected or confirmed infection (including but not limited to cUTI, cIAI, pneumonia, HAP/VAP, sepsis, or BSI) that requires hospitalization for treatment with IV antibiotics
Multiple-dose phase: Subject has a suspected or confirmed cUTI that requires hospitalization for treatment with IV antibiotics
5. If subject is a sexually active female of childbearing potential and has reached menarche or Tanner stage 3, subject 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

General Exclusion Criteria
Subjects who meet any of the following criteria will be excluded from the study.
1. Subject 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: Subject has an infection caused only by a confirmed Gram positive pathogen
3. Subject has a suspected or confirmed central nervous system (CNS) infection (eg, meningitis, brain abscess, shunt infection) or osteomyelitis (which would require prolonged antibiotic therapy)
4. Subject has cystic fibrosis
5. Single-dose phase: Subject has moderate or severe renal impairment based on estimated glomerular filtration rate (eGFR) (based on modified bed-side Schwartz equation [2009]) of < 60 mL/min/1.73 m2 at Screening
Multiple-dose phase: Subject has an eGFR (based on modified bed-side Schwartz equation [2009]) of < 15 mL/min/1.73 m2 at Screening
6. Subject has end-stage renal disease (ESRD), is on hemodialysis (HD), or receiving continuous venovenous hemofiltration (CVVH)
7. Subject is in refractory septic shock defined as persistent hypotension despite adequate fluid resuscitation or vasopressive therapy at Screening
8. Subject has severe neutropenia or is severely immunocompromised
9. Subject has multiorgan failure
10. Subjects with a life expectancy of < 30 days due to severity of a concurrent illness
11. Subject is a female who has a positive pregnancy test at Screening
12. Subject is a female who is breastfeeding
13. Subject has received any other investigational medicinal product (IMP) within 30 days
14. Subject has any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the subject or the quality of the study data, including acute trauma to the pelvis or urinary tract

Interventional

Cefiderocol (S-649266)

Cefiderocol plus Standard of Care antibiotics would be part of routine patient care for this study as a general rule, though monotherapy with cefiderocol is allowed  only if the subject's cUTI  is confirmed to be Gram negative only before starting treatment

None

Randomized

Open Label

Unspecified

Parallel

An open-label design is considered appropriate because placebo fluids would need to be administered for a blinded design and this would not be  ethical nor feasible in a pediatric population. Additionally, the comparison will be SOC, which could be one or more drug therapies, many of which will be IV (some will be oral). A double-blind design would mean placebo administration of all possible oral tablets would be necessary, which would be difficult. The antibacterial activity of cefiderocol is based on the inhibition of Gram-negative bacterial cell wall synthesis. cefiderocol is being developed to address the unmet medical need to treat carbapenem resistant infections caused by Gram-negative bacteria, namely, the treatment of infections caused by carbapenem-resistant, Gram-negative bacteria, including Enterobacteriaceae, such as E. coli and K. pneumoniae, and nonfermenters, such as P. aeruginosa, S. maltophilia, and A. baumannii, independent of the underlying mechanism of carbapenem resistance.

Phase II