A PHASE 2A, 2-PART, OPEN-LABEL, NON-RANDOMIZED, MULTICENTER, SINGLE AND MULTIPLE DOSE TRIAL TO EVALUATE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF CEFTAZIDIME AND AVIBACTAM IN NEONATES AND INFANTS FROM BIRTH TO LESS THAN 3 MONTHS OF AGE WITH SUSPECTED OR CONFIRMED INFECTIONS DUE TO GRAM-NEGATIVE PATHOGENS REQUIRING INTRAVENOUS ANTIBIOTIC TREATMENT (NOOR)

  • STATUS
    Recruiting
  • End date
    Dec 30, 2022
  • participants needed
    48
  • sponsor
    Pfizer
Updated on 16 September 2022

Summary

This study will assess the pharmacokinetics, safety, and tolerability of single and multiple doses of intravenous ceftazidime-avibactam in hospitalized infants and neonates from 26 weeks gestation to 3 months of age. In Part A of the study all patients will receive a single dose of ceftazidime-avibactam. In Part B all patients will received multiple doses of ceftazidime-avibactam. Efficacy will be assessed in the infants and neonates receiving multiple doses of ceftazidime-avibactam.

Description

This is a 2-part, Phase 2a, non-randomized, open-label multicenter, multinational study of intravenous ceftazidime-avibactam in hospitalized neonates and infants with suspected or confirmed bacterial infection. In Part A of the study, patients already receiving intravenous antibacterial therapy with another antibiotic will receive a single intravenous dose of ceftazidime-avibactam followed by observation for 48 hours and a Late Follow-Up assessment 4-5 weeks later. In Part B of the study, patients with suspected or confirmed Gram-negative bacterial infections requiring intravenous antibacterial therapy will receive multiple doses of intravenous ceftazidime-avibactam for up to 14 days. At the discretion of the investigator, patients may also receive other antibiotics if the infection is suspected to include Gram-positive bacteria, multi-drug resistant Gram-negative bacteria, or anaerobic bacteria. At the discretion of the investigator, patients may be switched to oral therapy or outpatient parenteral antimicrobial therapy with an alternative antibiotic after receiving intravenous ceftazidime-avibactam for at least 48 yhours. Clinical outcomes will be assessed at the End of Intravenous (EOIV) treatment with ceftazidime-avibactam, the End-of-Therapy (EOT), the Test-of-Cure (TOC) at 7-14 days after the last study therapy and at a Late Follow-Up (LFU) visit, 28-55 days after the last dose of ceftazidime-avibactam. Safety assessments will occur throughout the study. Ceftazidime-avibactam blood levels will be assessed during the first 12 hours after the single dose of ceftazidime-avibactam in Part A and during 12 hours after at least 3 consecutive doses of ceftazidime-avibactam in Part B.

Details
Condition Gram-negative Bacterial Infection
Treatment Part A: Single Dose Ceftazidime-Avibactam, Cohorts 1-3, Part B: Multiple-dose Ceftazidime-Avibactam, Cohorts 1-3
Clinical Study IdentifierNCT04126031
SponsorPfizer
Last Modified on16 September 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Evidence of a personally signed and dated informed consent document indicating that the subject's parent(s), legal guardian, or legally acceptable representative has been informed of all pertinent aspects of the study
Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Male or female neonates and infants with age at Screening
Cohort 1: Full term infants (gestational age ≥ 37 weeks) with chronological age >28 days to
<3 months (<89 days) or pre-term infants with corrected age >28 days to <3 months (<89
days). A maximum of 3 pre-term corrected age infants may be enrolled in each part (A and B)
of Cohort 1. Sites will be notified in writing if this limit is reached
Cohort 2: Full term neonates (gestational age ≥ 37 weeks) from birth to ≤ 28 days
Cohort 3: Pre-term neonates (gestational age ≥ 26 to <37 weeks) from birth to ≤ 28 days
Corrected age = Subtract the number of weeks born before 40 weeks of gestation from the
chronological age
Hospitalized and receiving intravenous antibacterial therapy for the treatment of a
Inclusion Criteria for Part A Subjects Only
suspected or confirmed bacterial infection
Inclusion Criteria for Part B Subjects Only
Hospitalized with suspected or confirmed aerobic Gram-negative bacterial infection
requiring intravenous antibacterial therapy
Subjects must meet at least 1 clinical and 1 laboratory criterion or meet at least 2
Clinical Criteria
of the clinical criteria
Bradycardia OR tachycardia OR rhythm instability
Hypothermia (<36ºC) OR fever (>38.5ºC)
Petechial rash OR sclerema neonatorum
Urine output 0.5 to 1 mL/kg/h OR hypotension OR mottled skin OR impaired peripheral
perfusion
Feeding intolerance OR poor suckling OR abdominal distension
Irritability
New onset or worsening of apnea episodes OR tachypnea episodes OR increased oxygen
Lethargy
requirements OR requirement for ventilation support
Hypotonia
Laboratory Criteria
Immature to total neutrophil ratio >0.2
White blood cell count ≤ 4.0 × 10^9/L OR ≥ 20.0 × 10^9/L
Hyperglycemia OR Hypoglycemia
Metabolic acidosis
Platelet count ≤ 100 × 10^9/L
C reactive protein (CRP) >15 mg/L OR procalcitonin ≥ 2 ng/mL

Exclusion Criteria

Investigator site staff members directly involved in the conduct of the study and
their family members, site staff members otherwise supervised by the Investigator, or
subjects who are Pfizer employees, including their family members, directly involved
in the conduct of the study
Participation in another clinical study involving investigational drug(s) within 30
Documented history of seizure
days prior to study entry and/or during this study participation or have previously
Active acute viral hepatitis or acute hepatic failure
participated in the current study or in another study of CAZ-AVI (in which an active
Known Clostridium difficile associated diarrhea
agent was received)
Use of potent inhibitors of organic anion transporters OAT1 and/or OAT3 (eg
probenecid, p-aminohippuric acid (PAH), or teriflunomide) are prohibited. This
Treatment with ceftazidime within 12 hours of CAZ-AVI administration
prohibition of OAT1 and/or OAT3 inhibitors also applies to the mothers of any neonates
Exclusion Criteria for Part A Subjects Only
or infants who are breast feeding during the trial
Other acute or chronic medical or laboratory abnormality that may increase the risk
associated with study participation or investigational product administration or may
Exclusion Criteria for Part B Subjects Only
interfere with the interpretation of study results and, in the judgment of the
Investigator, would make the subject inappropriate for entry into this study
Documented history of any hypersensitivity or allergic reaction to any beta-lactam
antibiotic
Refractory septic shock within 24 hours before screening that does not resolve after
minutes of vasopressor therapy
Moderate or severe renal impairment defined as serum creatinine ≥ 2 times the upper
limit of normal (ULN) for age OR urine output <0.5 mL/kg/h (measured over at least 8
hours) OR requirement for dialysis. Deterioration of renal function after enrollment
during Part B of the study will be handled on a case-by-case basis in discussion with
the Medical Monitor
Evidence of progressively fatal underlying disease, or life expectancy of ≤ 60 days
Requiring or currently taking antiretroviral therapy for human immunodeficiency virus
(HIV) or known HIV positive mother
Any condition (eg, cystic fibrosis, urea cycle disorders), antepartum/peripartum
factors, or procedures that would, in the opinion of the Investigator, make the
subject unsuitable for the study, place a subject at risk, or compromise the quality
of data
Subject received a blood or a blood component transfusion within 24 hours of the start
of CAZ AVI infusion
Subject is expected to be discharged less than 24 hours after the start of CAZ AVI
infusion
At study entry, subject has confirmed or strongly suspected infection with a pathogen
known to be resistant to CAZ-AVI or only a Gram-positive pathogen or viral, fungal, or
parasitic pathogens as the sole cause of infection
Confirmed or suspected central nervous system (CNS) infection (eg, meningitis, brain
abscess, subdural abscess)
Anticipated need for antibacterial therapy longer than 14 days (eg, osteomyelitis
endocarditis). This applies to both study treatment with CAZ-AVI as well as adjunctive
IV antibacterial treatment for suspected co infection with Gram-positive organisms or
multi drug resistant Gram-negative organisms
Receipt of more than 24 hours of nonstudy systemic antibacterial treatment for
Gram-negative organisms after culture and before administration of study doses of
CAZ-AVI. Empiric coverage with an aminoglycoside for suspected multidrug resistant
organisms is permitted, provided CAZ-AVI is initiated within 24 hours after culture
Intravenous treatment with chloramphenicol within 24 hours of administration of study
doses of CAZ-AVI
Subject is expected to be discharged less than 48 hours after the start of CAZ-AVI
infusion
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