A Study to Learn About the Study Medicine Aztreonam-Avibactam (ATM-AVI) in Infants and Newborns Admitted in Hospitals With Bacterial Infection (CHERISH)

NCT06462235 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: C36010102023-507757-15-01
• Study Type: interventional
• Target: 48
• Locations: 5 countries
• Sites: 26

Brief 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.

Conditions

Gram-negative Bacterial Infection

Keywords

gram-negative; aztreonam-avibactam; neonate; infant

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 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 Outcomes (7)

• Part B: Proportion of participants with each clinical outcome and with a favorable clinical outcome at end of IV study treatment (EOIV)

  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)

  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)

  7-14 days after the last study treatment

• Part B: Proportion of participants with a favorable microbiological response at TOC

  7-14 days after the last study treatment

• Part B: Counts and proportions of pathogens with each per-pathogen microbiological response at EOIV/EOT

  Up to 15 days after start of IV study treatment

Study Arms (2)

Part A, Cohorts 1-4

EXPERIMENTAL

Single dose pharmacokinetics.

Drug: Part A: ATM-AVI Single Dose, Cohorts 1-4

Part B, Cohorts 1-4

EXPERIMENTAL

Multi-dose pharmacokinetics and treatment

Drug: Part B: Multiple-dose ATM-AVI, Cohorts 1-4

Interventions

Part A: ATM-AVI Single Dose, Cohorts 1-4 DRUG

Single intravenous infusion of aztreonam-avibactam over 3 hours to assess pharmacokinetics, safety, and toleration.

Part A, Cohorts 1-4

Part B: Multiple-dose ATM-AVI, Cohorts 1-4 DRUG

Multiple intravenous infusions of aztreonam-avibactam over 3 hours, repeated every 6-8 hours up to 14 days to assess pharmacokinetics, safety, toleration, and efficacy.

Part B, Cohorts 1-4

Eligibility Criteria

• Age: Up to 39 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Hospitalized with age from birth \<9 months, including preterm birth
• Part A: Receiving IV antibiotics for treatment of suspected or confirmed bacterial infection, including but not limited to cIAI, cUTI, HAP/VAP, BSI, or sepsis.
• Part B: Suspected or confirmed gram-negative bacterial infection requiring IV antibiotics, including but not limited to cIAI, cUTI, HAP/VAP, BSI, or sepsis.
• Participants with any of the following characteristics/conditions will be excluded:
• Received any other investigational medicinal product within the longer of 30 days or 5 half-lives before enrollment.
• Any medical or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Severe renal impairment or known significant renal disease, as evidenced by elevated serum creatinine at screening, or urinary output \<0.5 mL/kg/h for 6 consecutive hours or requirement for dialysis.
• Part B Only: Received \>24 hours of systemic antibiotic treatment for gram-negative organisms at time of enrollment, unless documented treatment failure or lack of improvement in at least one objective sign or symptom of infection after ≥48 hours of antibiotics.

Sponsors & Collaborators

• Pfizer: lead
• AbbVie: collaborator

Study Sites (26)

Children's Hospital of Orange County Southwest Tower

Orange, California, 92868, United States

RECRUITING

Children's Hospital of Orange County

Orange, California, 92868, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, 46202, United States

RECRUITING

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

RECRUITING

Novak Center for Children's Health

Louisville, Kentucky, 40202, United States

RECRUITING

University of Louisville, Norton Children's Research Institute

Louisville, Kentucky, 40202, United States

RECRUITING

Tufts Medical Center

Boston, Massachusetts, 02111, United States

RECRUITING

Duke University - Main Hospital and Clinics

Durham, North Carolina, 27710, United States

RECRUITING

Memorial Hermann Hospital - Texas Medical Center

Houston, Texas, 77030, United States

RECRUITING

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

Sanatorio Sagrado Corazón

Ciudad Autónoma de Buenos Aires, Buenos Aires, 1039, Argentina

RECRUITING

Clinica Del Niño Y La Madre

Mar del Plata, Buenos Aires, 7600, Argentina

RECRUITING

Clinica Privada del Sol S.A

Córdoba, Córdoba Province, X5000IIH, Argentina

RECRUITING

Hospital del Niño Jesús

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

RECRUITING

Nirmal Hospital Pvt Ltd.

Surat, Gujarat, 395002, India

RECRUITING

RajaRajeswari Medical College and Hospital

Bengaluru, Karnataka, 560074, India

RECRUITING

Sahyadri Super Speciality Hospital

Pune, Maharashtra, 411006, India

RECRUITING

Medanta Hospital Lucknow

Lucknow, Uttar Pradesh, 226030, India

RECRUITING

Institute of Child Health

Kolkata, West Bengal, 700017, India

RECRUITING

Schneider Children's Medical Center

Petah Tikva, Central District, 49202, Israel

RECRUITING

Rambam Health Care Campus

Haifa, Northern District, 3109601, Israel

RECRUITING

Hsinchu Municipal Mackay Children's Hospital

Hsinchu, Hsinchu, 300046, Taiwan

RECRUITING

Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Hualien City, Hualien, 970, Taiwan

RECRUITING

Taichung Veterans General Hospital

Taichung, 407, Taiwan

RECRUITING

Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital

Taoyuan, 33305, Taiwan

RECRUITING

Related Links

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

MeSH Terms

Conditions

Gram-Negative Bacterial Infections

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections

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: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Non-randomized, 2-part with four age cohorts in each part

Study Record Dates

• First Submitted: May 28, 2024
• First Posted: June 17, 2024
• Study Start: September 25, 2024
• Primary Completion (Estimated): April 25, 2027
• Study Completion (Estimated): April 25, 2027
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

AR (4); US (11); IN (5); IL (2); TW (4)