E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Single dose: Pneumonia, cUTI, complicated intra-abdominal infections [cIAI], hospital acquired pneumonia [HAP]/ventilator-acquired pneumonia [VAP], and sepsis or bloodstream infections [BSI]). Multiple dose: cUTI |
|
E.1.1.1 | Medical condition in easily understood language |
Pneumonia, urinary tract infections, intra-abdominal infections and sepsi caused by Gram-negative bacterial infections |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 | 10040047 |
E.1.2 | Term | Sepsis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
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 |
|
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 pediatric subjects 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections To assess the pharmacokinetics (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 complicated urinary tract infection (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 |
|
E.2.2 | Secondary objectives of the trial |
|
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 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 for the multiple-dose phase. Hospitalized subject is 3 months to < 12 years of age at the time written informed consent/assent is obtained for the single-dose phase. Premature babies will not be restricted, but the subject must have an adjusted or postnatal age of 3 months. 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 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 |
|
E.4 | Principal exclusion criteria |
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 Bedside Schwartz equation [2009]) of < 60 mL/min/1.73 m2 at Screening Multiple-dose phase: Subject has an eGFR (based on modified Bedside 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 has experienced 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 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 15. Subject is receiving vasopressor therapy at screening |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetics (PK) and safety of cefiderocol in subjects 3 months to < 18 years of age. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
PK for single dose (cohort 2) - doses 1, 3, 3.5, 5 and 8
PK for single dose (cohorts 3 and 4) - doses 3, 5 and 8
PK for multiple dose (all cohorts) - doses 5 to 14 |
|
E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 |
Australia |
Czech Republic |
Greece |
Lithuania |
Mexico |
Panama |
Philippines |
Spain |
Ukraine |
United States |
|
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
|
28 days after last dose of study drug |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |