E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Including but not limited to complicated urinary tract infection [cUTI], complicated intra-abdominal infection [cIAI], hospital-acquired pneumonia [HAP]/ventilator-acquired pneumonia [VAP], and sepsis or bloodstream infections [BSI] |
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E.1.1.1 | Medical condition in easily understood language |
Severe infections caused by suspected or confirmed Gram-negative bacteria. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021881 |
E.1.2 | Term | Infections and infestations |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076918 |
E.1.2 | Term | Hospital acquired pneumonia |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065153 |
E.1.2 | Term | Ventilator associated pneumonia |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10046577 |
E.1.2 | Term | Urinary tract infections |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10079983 |
E.1.2 | Term | Complicated intra-abdominal infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003997 |
E.1.2 | Term | Bacteraemia |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053840 |
E.1.2 | Term | Bacterial sepsis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To assess the safety and tolerability of cefiderocol after single-dose administration in hospitalized paediatric subjects 3 months to < 18 years of age with suspected or confirmed aerobic Gram-negative bacterial infections • To assess the pharmacokinetics (PK) of cefiderocol after single-dose administration of cefiderocol in hospitalized paediatric subjects 3 months to < 18 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 paediatric subjects 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections • To assess the PK of cefiderocol after multiple-dose administration in hospitalized paediatric subjects 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections
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E.2.2 | Secondary objectives of the trial |
• Multiple-dose phase only: Whenever cefiderocol is admistered alone, to assess the clinical response at the Posttreatment visit (7 [±◦4] days following End of Treatment [EOT]) and at the End-of-study (EOS) visit, AND to assess the microbiological response at the Posttreatment visit (7 [±◦4] days) following EOT and EOS (if available). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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 boards/independent ethics committees [IRB's/IEC's] 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 for the single-dose phase. Hospitalized subject is 3 months to < 12 years of age at the time written informed consent/assent is obtained for the multiple-dose phase. Premature babies will not be restricted, but the subject must have an adjusted or postnatal age of 3 months. 4. Subject has a suspected or confirmed infection (including but not limited to cUTI, cIAI, HAP/VAP, sepsis, or BSI) 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
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E.4 | Principal exclusion criteria |
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. 5. Single-dose phase: Subject has moderate or severe renal impairment based on estimated glomerular filtration rate (eGFR) (based on Schwartz equation if ≥ 3 months to < 1 year of age and modified Bedside Schwartz equation if ≥ 1 to < 18 years of age) of < 60 mL/min/1.73 m2 at Screening. Multiple-dose phase: Subject has an eGFR (based on 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. Subject has end-stage renal disease (ESRD), is on hemodialysis (HD), or receiving continuous venovenous hemofiltration (CVVH) 7. Subject has experienced septic shock in the prior month or is in shock at the time of Screening 8. Subject has severe neutropenia or is severely immunocompromised 9. Subject has multiorgan failure 10. Subjects has 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 15. Subject is receiving vasopressor therapy at Screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety, tolerability and pharmacokinetics in patients treated with single dose or multiple dose. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety: prior to, during, and after administration of study drug Pharmacokinetic: Single dose PK sampling at 1, 3, 3.5, 5 and 8hr for children over 6yrs. For children under 6 years reduced PK sampling at 3, 5 and 8hrs. In the multiple dose part of the study the same timepoints of PK sampling listed above will be performed during one of the dosing intervals from the 6th to the 12th dose of cefiderocol. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Multiple dose phase - end of trial (EoT) and post treatment (7 days after EoT +/- 4 days) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Georgia |
Russian Federation |
Thailand |
Ukraine |
Belgium |
Estonia |
Hungary |
Latvia |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |