ATM-AVI for Bacterial Infections in Infants

(CHERISH Trial)

Recruiting at 27 trial locations

Overseen By Pfizer CT.gov Call Center

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Pfizer

Must be taking: IV antibiotics

Disqualifiers: Severe renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effects of a new combination medicine, ATM-AVI, for infections caused by gram-negative bacteria. ATM-AVI combines the antibiotic aztreonam with avibactam, which prevents bacteria from resisting antibiotic treatment. The trial has two parts: the first part administers a single dose to assess its function, and the second part uses multiple doses to treat confirmed or suspected infections. This trial targets newborns and infants up to 9 months old who are hospitalized with bacterial infections requiring IV antibiotics. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if participants must stop their current medications. However, participants in Part B should not have received more than 24 hours of systemic antibiotics for gram-negative infections unless there's a documented treatment failure.

Is there any evidence suggesting that ATM-AVI is likely to be safe for infants?

Research shows that aztreonam-avibactam (ATM-AVI) works well and is generally safe. Earlier studies found that ATM-AVI had a safety record similar to aztreonam, an antibiotic already in use. No new safety concerns have emerged with ATM-AVI, indicating it is usually safe. However, while ATM-AVI has been tested in other age groups, its safety for children under 18, including babies, remains unclear. This trial aims to learn more about how ATM-AVI affects very young patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bacterial infections?

Researchers are excited about Aztreonam-Avibactam (ATM-AVI) for treating bacterial infections in infants because it combines two powerful components that work together to combat resistant bacteria. Aztreonam is an established antibiotic that targets a wide range of bacteria, and Avibactam is a newer agent that blocks the enzymes some bacteria use to resist antibiotics. This combination is particularly promising against tough, drug-resistant infections that often don't respond well to existing treatments like standard beta-lactams or cephalosporins. By disabling the bacteria’s defense mechanisms, ATM-AVI offers hope for more effective management of severe infections in vulnerable infant populations.

What evidence suggests that ATM-AVI might be an effective treatment for bacterial infections in infants?

Research shows that the combination of aztreonam and avibactam (ATM-AVI) effectively treats infections caused by certain bacteria. Studies have found that this antibiotic pair is well-tolerated and can combat bacteria that often resist other treatments. Aztreonam acts as an antibiotic, while avibactam prevents bacteria from breaking down the antibiotic, enhancing its strength. Patients with serious infections have responded well to this treatment. In this trial, infants will receive ATM-AVI in different dosing regimens to assess its pharmacokinetics and effectiveness. This combination is especially promising because it targets bacteria typically resistant to many other antibiotics. ^{1 2 6 7 8}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

The CHERISH trial is for hospitalized newborns and infants up to 9 months old, including preterm babies. It's for those with suspected or confirmed bacterial infections caused by gram-negative bacteria. Babies already on antibiotics for over 24 hours may join Part B unless they're not improving after 48 hours of treatment.

Inclusion Criteria

I have severe kidney problems or need dialysis.

I am currently on IV antibiotics for a suspected or confirmed bacterial infection.

My baby is hospitalized and under 9 months old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Part A: Single Dose

Participants receive a single intravenous infusion of ATM-AVI to study safety and effects of a single dose

5 weeks

Multiple visits for infusion and assessments

Part B: Multiple Dose

Participants receive multiple intravenous infusions of ATM-AVI for 3-14 days as treatment for bacterial infection

7 weeks

Frequent visits for infusions and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-5 weeks

Final safety assessment, possibly by telephone

What Are the Treatments Tested in This Trial?

Interventions

• Aztreonam-Avibactam (ATM-AVI)

Trial Overview This study tests ATM-AVI, a combination antibiotic therapy given via IV (in the vein). Part A involves a single dose to check safety and effects, while Part B gives multiple doses to treat actual infections.

How Is the Trial Designed?

Group I: Part B, Cohorts 1-4 Experimental Treatment 1 Intervention

Multi-dose pharmacokinetics and treatment

Group II: Part A, Cohorts 1-4 Experimental Treatment 1 Intervention

Single dose pharmacokinetics.

Aztreonam-Avibactam (ATM-AVI) is already approved in European Union for the following indications:

Approved in European Union as Emblaveo for:

• Complicated intra-abdominal infections
• Hospital-acquired pneumonia
• Ventilator-associated pneumonia
• Complicated urinary tract infections
• Pyelonephritis
• Infections due to aerobic Gram-negative organisms in adults with limited treatment options

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

Aztreonam-avibactam shows strong in vitro effectiveness against metallo-beta-lactamase (MBL)-producing Enterobacterales, with MIC50 and MIC90 values indicating low concentrations needed for inhibition.

The drug combination is currently pending phase 3 clinical trials, suggesting it could be a promising treatment option for severe infections caused by resistant bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aztreonam-Avibactam Susceptibility Testing Program for Metallo-Beta-Lactamase-Producing Enterobacterales in the Antibiotic Resistance Laboratory Network, March 2019 to December 2020. Bhatnagar, A., Boyd, S., Sabour, S., et al.[2022]

Aztreonam/avibactam (ATM-AVI) demonstrated high efficacy against Klebsiella pneumoniae isolates, with over 99.9% of isolates inhibited at a minimum inhibitory concentration (MIC) of ≤4 mg/L, indicating strong potential as a treatment option.

The study found that ATM-AVI is particularly effective against meropenem-resistant strains, with all tested meropenem-resistant metallo-β-lactamase positive isolates inhibited at an MIC of ≤0.5 mg/L, showcasing its importance in combating antibiotic-resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro activity of aztreonam/avibactam against a global collection of Klebsiella pneumoniae collected from defined culture sources in 2016 and 2017. Esposito, S., Stone, GG., Papaparaskevas, J.[2021]

In a study of 102 patients with bloodstream infections caused by metallo-β-lactamase-producing Enterobacterales, the combination of ceftazidime-avibactam (CAZ-AVI) and aztreonam (ATM) significantly reduced the 30-day mortality rate to 19.2%, compared to 44% in those treated with other active antibiotics.

The CAZ-AVI + ATM treatment also led to lower clinical failure rates at day 14 and shorter hospital stays, indicating its potential as a more effective therapy for these serious infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Ceftazidime-avibactam Plus Aztreonam in Patients With Bloodstream Infections Caused by Metallo-β-lactamase-Producing Enterobacterales. Falcone, M., Daikos, GL., Tiseo, G., et al.[2021]

Aztreonam-avibactam (ATM-AVI) effectively treats serious infections caused by multidrug-resistant pathogens, with its bactericidal activity primarily enhanced by avibactam rather than just preventing aztreonam degradation.

In vitro studies showed that the enhancement of aztreonam's effect was the main contributor to its combined bactericidal activity, suggesting that when choosing a β-lactamase inhibitor, its ability to boost β-lactam efficacy should be prioritized.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semimechanistic Pharmacodynamic Modeling of Aztreonam-Avibactam Combination to Understand Its Antimicrobial Activity Against Multidrug-Resistant Gram-Negative Bacteria. Chauzy, A., Gaelzer Silva Torres, B., Buyck, J., et al.[2020]

A new pre-diffusion assay using ceftazidime/avibactam disks can effectively predict the in vitro efficacy of the aztreonam/avibactam (ATM-AVI) combination against NDM-producing Klebsiella, based on a study of 113 bacterial isolates.

The study found that while 38.4% of isolates were susceptible to aztreonam alone, all isolates had low minimum inhibitory concentrations (MICs) for ATM-AVI, indicating strong potential for this combination therapy in treating infections caused by these resistant bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A simple disk pre-diffusion test to predict in vitro aztreonam/avibactam activity against NDM-producing Klebsiella pneumoniae complex. Lima, KO., de Lima, AV., Rocha, DADC., et al.[2022]

The drug combination aztreonam/avibactam (ATM-AVI) showed potent antimicrobial activity against 99.9% of Enterobacterales isolates, including those resistant to multiple drugs and producing metallo-β-lactamases (MBLs), based on a study of 18,713 clinical isolates collected globally in 2019.

ATM-AVI maintained high efficacy against MBL-positive and carbapenemase-producing strains, suggesting it could be a valuable treatment option for serious infections caused by these difficult-to-treat bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro activity of aztreonam/avibactam against isolates of Enterobacterales collected globally from ATLAS in 2019. Rossolini, GM., Stone, G., Kantecki, M., et al.[2022]

Avibactam, a new β-lactamase inhibitor, was found to have similar pharmacokinetics in healthy young and elderly volunteers, indicating that age does not necessitate dosage adjustments for this drug.

The study reported that the most common side effect was mild bruising at the injection site, suggesting that avibactam is generally safe and well-tolerated among different age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of age and sex on the pharmacokinetics and safety of avibactam in healthy volunteers. Tarral, A., Merdjan, H.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06462235

NCT06462235 | A Study to Learn About the ... 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 ...

2. pfizer.com pfizer.com/news/press-release/press-release-detail/phase-3-studies-pfizers-novel-antibiotic-combination-offer

Phase 3 Studies of Pfizer's Novel Antibiotic Combination ... Data support that antibiotic aztreonam -avibactam (ATM-AVI) is effective and well-tolerated in treating infections caused by Gram-negative ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11687205/

Aztreonam–avibactam: The dynamic duo against multidrug ... The use of CAZ‐AVI has shown effectiveness in treating serious infections caused by CRE. , Avibactam, the β‐lactamase inhibitor present in both ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05639647

NCT05639647 | Study of 2 Medicines (Aztreonam and ... The purpose of this study is to evaluate how Aztreonam (ATM) and Avibactam (AVI) are processed in pediatric participants.

5. pfizerclinicaltrials.com pfizerclinicaltrials.com/find-a-trial/nct06462235-gram-negative-bacterial-infection-trial

Clinical Trial for Gram-negative Bacterial Infection. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03580044

NCT03580044 | Efficacy, Safety, and Tolerability of ATM- ... Phase 3 study to determine the efficacy, safety, and tolerability of aztreonam- avibactam (ATM- AVI) versus best available therapy (BAT) in the treatment of ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/217906Orig1s000lbl.pdf

HIGHLIGHTS OF PRESCRIBING INFORMATION These ... Prescribing EMBLAVEO in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk ...

8. ema.europa.eu ema.europa.eu/en/documents/product-information/emblaveo-epar-product-information_en.pdf

Emblaveo, INN-aztreonam / avibactam Paediatric population. The safety and efficacy of Emblaveo in paediatric patients < 18 years of age have not yet been established. No data are ...