A pharmacokinetics and safety study of cefiderocol in hospitalized pediatric patients from birth to less than 3 months of age with suspected or confirmed Gram-negative bacterial infections

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Shionogi B.V.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Decision date (initial)

2023-10-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Shionogi BV

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Therapy

1. To assess the PK of cefiderocol after single-dose administration in hospitalized pediatric patients from birth to < 3 months of age with suspected or confirmed aerobic Gram-negative bacterial infections, including but not limited to, cUTI, cIAI, HABP/VABP, and BSI/sepsis
2. To assess the PK of cefiderocol after multiple-dose administration in hospitalized pediatric patients from birth to < 3 months of age with suspected or confirmed aerobic Gram-negative bacterial infections, including but not limited to, cUTI, cIAI, HABP/VABP, and BSI/sepsis

Secondary objectives 3

1. To assess the safety and tolerability of cefiderocol after single-dose administration in hospitalized pediatric patients from birth to < 3 months of age with suspected or confirmed aerobic Gram-negative bacterial infections
2. To assess the safety and tolerability of cefiderocol after multiple-dose administration in hospitalized pediatric patients from birth to < 3 months of age with suspected or confirmed aerobic Gram-negative bacterial infections
3. To evaluate all-cause mortality at Day 28

Conditions and MedDRA coding

Aerobic Gram-negative bacterial infections

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002133-PIP01-17

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Written informed consent has been provided by parent(s) or legally authorized representative(s) (LAR) 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 kg.
3. Require systemic IV antibiotic treatment for suspected or confirmed aerobic Gram-negative infections, including but not limited to, cUTI, cIAI, HABP/VABP, 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 Gramnegative infection

Exclusion criteria 13

1. Documented history of any moderate or severe 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. Life expectancy of < 72 hours after enrollment
3. Urine output < 1.0 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 in the Protocol 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 mg/dL (133 μmol/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 patient 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. 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 (eg, 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 patients with suspected CNS infection who do not have a lumbar puncture (LP) but who are treated for potential CNS infection, patients who have evidence suggestive of CNS infection based on LP results (polymorphonuclear pleocytosis, hypoglycorrhachia, and increased protein concentration), regardless of culture results, and patients with a LP with organisms on Gram stain or culture-positive CSF

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Cmax, AUC0-inf, and t1/2 after single dose
2. Cmax, AUC0-τ, and t1/2 after a minimum of 4 doses of cefiderocol

Secondary endpoints 5

1. Adverse events
2. Vital signs
3. Physical examinations
4. Clinical laboratory assessments
5. Death

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Shionogi B.V.

Sponsor organisation

Shionogi B.V.

Address

Herengracht 464

City

Amsterdam

Postcode

1017 CA

Country

Netherlands

Scientific contact point

Organisation

Shionogi B.V.

Contact name

Medical Sciences

Public contact point

Organisation

Shionogi B.V.

Contact name

Medical Sciences

Third parties 10

Locations

3 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications