ATM-AVI for Bacterial Infections in Infants

(CHERISH Trial)

Recruiting at 15 trial locations

Overseen By Pfizer CT.gov Call Center

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Pfizer

Must be taking: IV antibiotics

Disqualifiers: Severe renal impairment, others

No Placebo Group

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

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.

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 Aztreonam-Avibactam (ATM-AVI) safe for humans?

A study on avibactam, a component of ATM-AVI, found it to be safe and well-tolerated in healthy young and elderly volunteers. ^{1 2 3 4 5}

How is the drug ATM-AVI different from other treatments for bacterial infections in infants?

ATM-AVI is unique because it combines aztreonam and avibactam to effectively treat infections caused by drug-resistant bacteria, including those producing metallo-β-lactamases (MBLs), which are difficult to treat with standard antibiotics. Avibactam enhances the effect of aztreonam by preventing its breakdown and boosting its ability to kill bacteria. ^{3 4 5 6 7}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Aztreonam-Avibactam (ATM-AVI) (Anti-bacterial)

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.

Participant Groups

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.

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Effect of age and sex on the pharmacokinetics and safety of avibactam in healthy volunteers. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

In vitro activity of aztreonam/avibactam against isolates of Enterobacterales collected globally from ATLAS in 2019. [2022]

4. Netherlands 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. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

A simple disk pre-diffusion test to predict in vitro aztreonam/avibactam activity against NDM-producing Klebsiella pneumoniae complex. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Ceftazidime-avibactam Plus Aztreonam in Patients With Bloodstream Infections Caused by Metallo-β-lactamase-Producing Enterobacterales. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Semimechanistic Pharmacodynamic Modeling of Aztreonam-Avibactam Combination to Understand Its Antimicrobial Activity Against Multidrug-Resistant Gram-Negative Bacteria. [2020]