A Study to Learn About the Study Medicine Aztreonam-Avibactam (ATM-AVI) in Infants and Newborns Admitted in Hospitals With Bacterial Infection (CHERISH)
NCT Number: NCT06462235
Acronym: CHERISH
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Gram-negative Bacterial Infection
Interventions: DRUG: Part A: ATM-AVI Single Dose, Cohorts 1-4|DRUG: Part B: Multiple-dose ATM-AVI, Cohorts 1-4
Sponsor: Pfizer
Collaborators: AbbVie
Sex: ALL
Age: CHILD
Enrollment: 48
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: BASIC_SCIENCE
Start Date: 2024-09-16
Completion Date: 2027-09-27
Locations: Bristol Myers Squibb Children's Hospital at Robert Wood Johnson University Hospital, New Brunswick, New Jersey, 08901, United States|Rutgers University, New Brunswick, New Jersey, 08901, United States|Rambam Health Care Campus, Haifa, Hatsafon, 3109601, Israel|Taichung Veterans General Hospital, Taichung, 407, Taiwan|Chang Gung Medical Foundation-Linkou Branch, Taoyuan, 333, Taiwan

Summary:
The purpose of this study is to learn about the safety and effects of ATM-AVI for the possible treatment of infections caused by a type of bacteria called gram-negative bacteria.

The study medicine is a combination of an antibiotic, aztreonam (ATM), and another medicine, avibactam (AVI), which is used to help stop bacteria from being resistant to antibiotics. Antibiotics are medicines that fights bacteria and infections.

The study will include newborns and infants up to 9 months of age who are admitted in the hospital.

The study is conducted in 2 parts: Part A and Part B.

In Part A, all participants will receive a single intravenous (injected directly into a vein) infusion of ATM-AVI. This is to study the safety and effects of a single amount.

In Part B, all participants will receive multiple intravenous infusions of ATM-AVI as treatment for a possible or confirmed infection with gram-negative bacteria.

Primary Outcome Measures: Maximum Predicted Plasma Concentration (Cmax) of ATM and AVI, Cmax is the maximum plasma concentration of ATM and AVI as population pharmacokinetic (popPK) analysis predicts., Up to Day 15|Area under the Concentration-Time Curve (AUC) of ATM-AVI, AUC is a measure of the plasma concentration of ATM and AVI overtime as popPK analysis predicts., Up to Day 15|Plasma Elimination Half-Life (t1/2), Half-life is the time measured for the plasma concentration of ATM and AVI to decrease by one half as popPK analysis predicts., Up to Day 15|Apparent Clearance (CL), ATM and AVI clearance is a quantitative measure of the rate at which ATM and AVI are removed from the blood (rate at which ATM and AVI are metabolized or eliminated by normal biological processes). Clearance obtained after intravenous infusion dose (apparent clearance) is influenced by the fraction of the dose absorbed., Up to Day 15|Plasma concentrations of ATM and AVI by nominal sampling time, Plasma concentrations of ATM and AVI on Day 1 and at steady state (Day 2 or later) will be summarized by the nominal sampling time using descriptive statistics (eg number, mean, standard deviation)., Up to Day 15|Proportion of Participants reporting Adverse Events (AE), Proportion of participant AE reports of vital signs, physical examinations, and clinical laboratory tests overall and by age cohort. For each AE the last assessment made prior to the first dose of study drug will be defined as the baseline., Baseline up to Day 50|Proportion of Participants reporting Serious Adverse Events (SAE), Proportion of participant SAE reports of vital signs, physical examinations, and clinical laboratory tests overall and by age cohort. For each SAE the last assessment made prior to the first dose of study drug will be defined as the baseline., Baseline up to Day 50|Proportion of Participants reporting AEs leading to discontinuation of study drug, Proportion of Participants reporting AEs leading to discontinuation of study drug from baseline. For each discontinuation the last assessment made prior to the first dose of study drug will be defined as the baseline., Baseline up to Day 50|Proportion of Participants reporting AEs resulting in death, Proportion of Participants reporting AE resulting in death from baseline. For each death the last assessment made prior to the first dose of study drug will be defined as the baseline., Baseline up to Day 50|Proportion of Participants reporting liver injury and acute kidney injury, Proportion of Participants reporting liver injury and acute kidney injury from baseline. For each report of liver and acute kidney injury the last assessment made prior to the first dose of study drug will be defined as the baseline., Baseline up to Day 50
Secondary Outcome Measures: Part B: Proportion of participants with each clinical outcome and with a favorable clinical outcome at end of IV study treatment (EOIV), Clinical Cure is defined baseline signs and symptoms improved such that no further antimicrobial treatment is required for an aerobic gram-negative baseline infection. Participants who receive treatment for gram-positive organisms or adjunctive therapy for Pseudomonas aeruginosa, as allowed per protocol, can still have a response of cure. Clinical improvement is defined as baseline signs and symptoms sufficiently improved to allow switching to an oral antibiotic treatment. A favorable outcome is clinical cure or clinical improvement. Failure is defined as a requirement for further antibiotic treatment, including following premature discontinuation due to an adverse event, or death after receiving at least 48 hours of treatment. Indeterminant is defined as data not available for evaluation of efficacy for any reason., Up to 15 days after start of IV study treatment|Part B: Proportion of participants with each clinical outcome and with a favorable clinical outcome at end of treatment (EOT), EOT is only applicable for participants switched to an oral antibiotic treatment. Possible outcomes are cure, failure, or indeterminant., Within 48 hours after last dose of oral switch treatment|Part B: Proportion of participants with each clinical outcome and with a favorable clinical outcome at test of cure (TOC), Possible outcomes are cure, failure, or indeterminant., 7-14 days after the last study treatment|Part B: Proportion of participants with a favorable microbiological response at TOC, A favorable response is eradication or presumed eradication. Eradication is absence of the causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication is when a repeat culture was not performed and the clinical response is cure., 7-14 days after the last study treatment|Part B: Counts and proportions of pathogens with each per-pathogen microbiological response at EOIV/EOT, Possible outcomes are eradication, presumed eradication, persistence, presumed persistence or indeterminate. Presumed eradication/persistence based on repeat culture not performed and clinical outcome of cure/failure. Persistence is the causative pathogen is still present from an appropriately obtained specimen at the site of the infection. Indeterminant includes participant lost to follow-up or death after receiving less than 48 hours of study treatment., Up to 15 days after start of IV study treatment|Part B: Counts and proportions of pathogens with each per-pathogen microbiological response at TOC, Possible outcomes are eradication, presumed eradication, persistence, presumed persistence or indeterminate., 7-14 days after the last study treatment|Part B: Counts and proportions of participants with emergent infections (new infections or superinfections) during the study, Superinfection is defined as emergence of a new pathogen associated with worsening signs and symptoms of infection and a requirement for additional antibiotics during the period up to and including EOIV/EOT. New infection is defined as emergence of a new pathogen associated with worsening signs and symptoms of infection and a requirement for additional antibiotics during the period after EOIV/EOT., Through study completion, up to Day 50