Study of 2 Medicines (Aztreonam and Avibactam) Compared to Best Available Therapy for Serious Gram-negative Infections

NCT05639647 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: C36010082022-501575-12-00
• Study Type: interventional
• Target: 48
• Locations: 8 countries
• Sites: 24

Brief Summary

The purpose of this study is to evaluate how Aztreonam (ATM) and Avibactam (AVI) are processed in pediatric participants. This study also aims to understand participant safety and effects in pediatric participants. The study is seeking participants who are:

• 9 months to less than 18 years of age
• Hospitalized
• Suspected/known to have a gram-negative infection
• Receiving intravenous (iv, given directly into a vein) antibiotics
• Being treated for complicated infections of various body parts that includes the abdomen, urinary tract, blood stream, and lungs.
• Participants will receive either ATM-AVI or best available therapy (BAT).
• Both therapies will be given through a vein.
• Participants with complicated abdominal infections will also receive iv Metronidazole (MTZ). Patients with cIAI and Cockayne Syndrome are excluded due to a risk of severe hepatotoxicity with the use of MTZ. - Participants on ATM-AVI treatment who have anaerobic infections will also receive iv MTZ at the study doctor's discretion.
• The iv dose of ATM-AVI will be based on the participant's weight and kidney function.
• The study doctor will determine the iv dose of BAT.
• During the first 2 study days, participants on ATM-AVI therapy will have 5 blood draws in small quantities.
• Starting on day 4, the study doctor will decide if participants may be switched to oral therapy.
• Participants will receive a maximum of 14 days of ATM-AVI treatment.
• After discharge from the hospital, 1 study visit may be required.
• Depending on the participant's response, the study duration will be from 33 to 50 days.
• The investigator will contact participants by phone 28 to 35 days after the last study treatment to check participants health status.

Conditions

Gram-negative Bacterial Infections

Keywords

Gram-negative bacterial infections

Outcome Measures

Primary Outcomes (10)

• 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 15 Days

• Minimum Predicted Trough Plasma Concentration (Cmin) of ATM and AVI

  Cmin is the minimum trough plasma concentration of ATM and AVI as popPK analysis predicts.

  Up to 15 Days

• 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 15 Days

• Plasma Decay 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 15 Days

• 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 15 Days

• 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

  Proportion of Participants reporting AEs leading to discontinuation 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 of ATM-AVI relative to Best Available Therapy (BAT)

  Proportion of Participants reporting liver injury and acute kidney injury of ATM-AVI relative to Best Available Therapy (BAT) 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 Outcomes (6)

• Perentage of participants with favorable clinical response (CR) at end of iv study treatment (EOIV)

  Up to 15 days after iv study drug treatment

• Percentage of Participants With Favorable Clinical Response (CR) at End of Treatment (EOT)

  EOT within 48 hours after last dose of oral switch therapy or at time of premature discontinuation of study drug or early withdrawal from study

• Percentage of Participants With Favorable Clinical Response (CR) at Test of Cure (TOC)

  Up to 15 Days after last study treatment

• Percentage of participants with Favorable Microbiological Response at end of iv study drug treatment (EOIV)

  EOIV within 24 hours after last iv study drug infusion

• Percentage of Participants with Favorable Microbiological Response at End of Treatment (EOT)

  EOT within 48 hours after last dose of oral switch therapy or at time of premature discontinuation of study drug or early withdrawal from study

Study Arms (2)

ATM-AVI

EXPERIMENTAL

ATM-AVI administered iv every 6 or 8 hours and dosed according to participant's weight and kidney function for up to 14 days depending on response. At the investigator's discretion, the participant may be switched to oral therapy after 3 days of iv ATM-AVI therapy

Drug: ATM-AVI

Best available therapy (BAT)

ACTIVE COMPARATOR

BAT will be selected by the investigator and administered iv. At the investigator's discretion, the participant may be switched to oral therapy after 3 days of iv BAT

Drug: BAT

Interventions

ATM-AVI DRUG

A drug specifically designed to treat resistant gam-negative bacterial infections

Also known as: aztreonam plus avibactam

ATM-AVI

BAT DRUG

BAT will be selected by the investigator and administered iv as appropriate for the selected drug(s)

Also known as: Best available therapy

Best available therapy (BAT)

Eligibility Criteria

• Age: 9 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participants ≥9 months to \<18 years of age at Screening; Female (post-menarchal) participants must have a negative serum/urine pregnancy test (β hCG sensitivity ≥25 mIU/mL).
• Suspected/confirmed cIAI, cUTI, HAP/VAP, or BSI with gram-negative pathogens.
• Require hospitalization and IV antibiotic treatment.

You may not qualify if:

• Participants with any of the following characteristics/conditions will be excluded:
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Gram-negative species not expected to respond to ATM AVI ≤14 days.
• Pregnant or breastfeeding; fertile male/female unwilling/unable to use effective contraception for at ≥7 days (males) or ≥28 days (females) after last ATM-AVI infusion.
• (HAP/VAP only):
• Microbiologically known or high likelihood of monomicrobial infection with a gram-positive organism, lung abscess, pleural empyema, or post-obstructive pneumonia, lung or heart transplant.
• Received \>24 hours of systemic antibiotics during the 48 hours before randomization unless participant has documented treatment failure after at least 48 hours of antibiotic therapy.
• Current use of any prohibited concomitant medication(s) or unwilling/unable (Cockayne Syndrome patients with cIAI are excluded) to use MTZ or having received previous investigational drug(s) or vaccine ≤30 days or 5 half-lives before randomization (whichever is longer).
• CrCL ≤15 mL/min/1.73 m2 (eCrCl or eGFR calculation based on age).
• Non-infectious related screening ALT or AST \>3 x ULN, ALP \>3 x ULN and/or TBili \>2 x ULN (\> 3 x ULN for Gilbert's syndrome).
• Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (24)

Rady Children's Hospital

San Diego, California, 92123, United States

RECRUITING

Weill Cornell Medicine-New York Presbyterian Hospital

New York, New York, 10021, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Le Bonheur Children's Hospital

Memphis, Tennessee, 38103, United States

RECRUITING

Beijing Children's Hospital, Capital Medical University

Beijing, Beijing Municipality, 100045, China

NOT YET RECRUITING

Guangzhou Women and Children's Medical Center

Guangzhou, Guangdong, 510623, China

NOT YET RECRUITING

Shanghai Children's Medical Center

Shanghai, 200127, China

RECRUITING

University General Hospital of Heraklion

Heraklion, Irakleío, 715 00, Greece

RECRUITING

Ippokrateio General Hospital of Thessaloniki

Thessaloniki, Kentrikí Makedonía, 546 42, Greece

RECRUITING

Semmelweis Egyetem

Budapest, 1083, Hungary

RECRUITING

Semmelweis Egyetem

Budapest, 1094, Hungary

RECRUITING

RajaRajeswari Medical College and Hospital

Bangalore, Karnataka, 560074, India

RECRUITING

Medanta Hospital Lucknow

Lucknow, Uttar Pradesh, 226030, India

RECRUITING

Institute of Child Health

Kolkata, West Bengal, 700017, India

RECRUITING

Hospital Germans Trias i Pujol

Badalona, Barcelona [barcelona], 08916, Spain

RECRUITING

Hospital Sant Joan de Déu

Esplugues de Llobregat, Barcelona [barcelona], 08950, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, Madrid, Comunidad de, 28046, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hsinchu Municipal Mackay Children's Hospital

Hsinchu, Hsinchu, 300046, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 100225, Taiwan

RECRUITING

Chang Gung Medical Foundation-Linkou Branch

Taoyuan District, 333, Taiwan

RECRUITING

Cukurova Universty

Sarçam, Adana, 01250, Turkey (Türkiye)

ACTIVE NOT RECRUITING

Istanbul Universitesi Istanbul Tıp Fakultesi Hastanesi

Istanbul, İ̇stanbul, 34093, Turkey (Türkiye)

ACTIVE NOT RECRUITING

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Gram-Negative Bacterial Infections

Interventions

Aztreonam; avibactam

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Monobactams; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Central Study Contacts

Pfizer CT.gov Call Center

CONTACT

1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Blinded observer assigned by each site
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, open-label, parallel study comparing ATM-AVI with or without metronidazole (MTZ) compared to BAT for the treatment of serious gram-negative bacterial infections. For every 3 participants assigned to ATM-AVI therapy one will be assigned to BAT.

Study Record Dates

• First Submitted: October 24, 2022
• First Posted: December 6, 2022
• Study Start: April 18, 2023
• Primary Completion (Estimated): August 17, 2026
• Study Completion (Estimated): August 17, 2026
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

IN (3); US (4); HU (2); TU (2); CN (3); ES (5); TW (3); GR (2)