Clinical trial NCT04215991: A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Cefiderocol in Hospitalized Pediatric Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gram-negative Bacterial Infections
Hospital Acquired Bacterial Pneumonia (HABP)
Complicated Urinary Tract Infection (cUTI)
Ventilator Associated Bacterial Pneumonia (VABP)
Lead sponsor: Shionogi Inc.
Sponsor class: INDUSTRY
First posted: 2020-01-02
Enrollment: 91
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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 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: 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.

Primary outcomes:
measure: Number of Participants with Adverse Events in the Single Dose Phase
timeFrame: 28 days
measure: Maximum Observed Plasma Concentration (Cmax) of Cefiderocol in the Single Dose Phase
timeFrame: Day 1, 1 (cohort 2 only), 3, 3.5 (cohort 2 only), 5, and 8 hours after the start of infusion
measure: Area Under the Plasma Concentration Time Curve Extrapolated from Time 0 to Infinity (AUCinf) of Cefiderocol in the Single Dose Phase
timeFrame: Day 1, 1 (cohort 2 only), 3, 3.5 (cohort 2 only), 5, and 8 hours after the start of infusion
measure: Apparent Terminal Elimination Half-life of Cefiderocol in the Single Dose Phase
timeFrame: Day 1, 1 (cohort 2 only), 3, 3.5 (cohort 2 only), 5, and 8 hours after the start of infusion
measure: Number of Participants with Adverse Events in the Multiple Dose Phase
timeFrame: Up to 28 days after last dose (33 to 42 days depending on treatment duration)
measure: Maximum Observed Plasma Concentration of Cefiderocol in the Multiple Dose Phase
timeFrame: 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
measure: Area Under the Plasma Concentration Time Curve Over the Dosing Interval τ (AUC0-τ) of Cefiderocol in the Multiple Dose Phase
timeFrame: 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
measure: Apparent Terminal Elimination Half-life of Cefiderocol in the Multiple Dose Phase
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa Stead Family Children's Hospital
state: Iowa
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: South Brisbane
country: Australia
facility: Queensland Children's Health Precinct Level 8, Centre for Children's Health Research 62 Graham Street
state: Queensland
city: Tbilisi
country: Georgia
facility: JSC "EVEX Medical Corporation"- M Lashvili Childrens Central Hospital
city: Tbilisi
country: Georgia
facility: Ltd Unimedi Kakheti Childrens New Clinic
city: Heraklion
country: Greece
facility: Heraklion University General Hospital
state: Crete
city: Larissa
country: Greece
facility: University General Hospital of Larissa
state: Thessaly
city: Chaidari
country: Greece
facility: University Hospital "ATTIKON" 3rd Pediatric Clinic of NKUA
city: Thessaloniki
country: Greece
facility: Hippokration Hospital 3rd Pediatric Clinic of AUTH Konstantinoupoleos 49
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki Papageorgiou
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kauno klinikos
city: Klaipeda
country: Lithuania
facility: Klaipeda Children's Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Hospital 278, El retiro, Torre Piso 10, Infectología Ped.
state: Jalisco
city: Ciudad de México
country: Mexico
facility: 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
city: Ciudad de Panama
country: Panama
facility: Hospital de Especialidades Ped Via España y Calle Zarak
city: Panama City
country: Panama
facility: Hospital del Niño, Epidemiologia
city: Cebu City
country: Philippines
facility: Chong Hua Hospital
city: Iloilo City
country: Philippines
facility: Western Visayas and Medical Center
city: Manila
country: Philippines
facility: Manila Doctor's Hospital
city: Barcelona
country: Spain
facility: Hospital Val d'Hebron
city: Barcelona
country: Spain
facility: Hospital del Mar, Passeig Marítim 25-29
city: Kharkiv
country: Ukraine
facility: Municipal Noncommercial Enterprise of Kharkiv Regional Council " V.I.Shapoval Regional Clinical Center of Urology and Nephrology", Department of Children Urology # 7
city: Vinnytsia
country: Ukraine
facility: Vinnytsia Regional Children's Hospital
city: Zaporizhzhia
country: Ukraine
facility: Zaporizhzhia Regional Children Clinical Hospital
Study officials:
affiliation: Shionogi
name: Shionogi Clinical Trials Administrator Clinical Support Help Line
role: STUDY_DIRECTOR
References: