Gram-negative Bacterial InfectionPhase 2CHERISHNCT06462235
A Study to Learn About the Study Medicine Aztreonam-Avibactam (ATM-AVI) in Infants and Newborns Admitted in Hospitals With Bacterial Infection (CHERISH)
A Phase 2 study testing Part A: ATM-AVI Single Dose, Cohorts 1-4 and Part B: Multiple-dose ATM-AVI, Cohorts 1-4 in people with Gram-negative Bacterial Infection, run by Pfizer at 32 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 39 weeks
- Conditions the study is for
- Gram-negative Bacterial Infection
- What is being tested?
- Part A: ATM-AVI Single Dose, Cohorts 1-4 and Part B: Multiple-dose ATM-AVI, Cohorts 1-4
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 32 sitesin 9 countries
- Study dates
- 25 Sep 2024to 25 Apr 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 39 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Participants must meet the following key inclusion criteria to be eligible for enrollment into the study:
- 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.
Show all 9Show fewer
- 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.
Who cannot join
None listed.
Trial locations and contacts
32 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
32 sites in 9 countries
United States11 sites, 11 recruiting
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
- Recruiting
Tufts Medical Center
Boston, Massachusetts, 02111
- Recruiting
Duke University - Main Hospital and Clinics
Durham, North Carolina, 27710
- Recruiting
Memorial Hermann Hospital - Texas Medical Center
Houston, Texas, 77030
- Recruiting
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
- Recruiting
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, 46202
- Recruiting
Norton Children's Hospital
Louisville, Kentucky, 40202
- Recruiting
Novak Center for Children's Health
Louisville, Kentucky, 40202
- Recruiting
University of Louisville, Norton Children's Research Institute
Louisville, Kentucky, 40202
- Recruiting
Children's Hospital of Orange County Southwest Tower
Orange, California, 92868
- Recruiting
Children's Hospital of Orange County
Orange, California, 92868
India5 sites, 5 recruiting
- Recruiting
RajaRajeswari Medical College and Hospital
Bengaluru, Karnataka, 560074
- Recruiting
Institute of Child Health
Kolkata, West Bengal, 700017
- Recruiting
Medanta Hospital Lucknow
Lucknow, Uttar Pradesh, 226030
- Recruiting
Sahyadri Super Speciality Hospital
Pune, Maharashtra, 411006
- Recruiting
Nirmal Hospital Pvt Ltd.
Surat, Gujarat, 395002
Argentina4 sites, 4 recruiting
- Recruiting
Sanatorio Sagrado Corazón
Ciudad Autónoma de Buenos Aires, Buenos Aires, 1039
- Recruiting
Clinica Privada del Sol S.A
Córdoba, Córdoba Province, X5000IIH
- Recruiting
Clinica Del Niño Y La Madre
Mar del Plata, Buenos Aires, 7600
- Recruiting
Hospital del Niño Jesús
San Miguel de Tucumán, Tucumán Province, 4000
Taiwan4 sites, 4 recruiting
- Recruiting
Hsinchu Municipal Mackay Children's Hospital
Hsinchu, Hsinchu, 300046
- Recruiting
Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
Hualien City, Hualien, 970
- Recruiting
Taichung Veterans General Hospital
Taichung, 407
- Recruiting
Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital
Taoyuan, 33305
Bulgaria2 sites, 2 recruiting
- Recruiting
UMHAT Deva Maria
Burgas, 8000
- Recruiting
Umhat Kanev
Rousse, 7002
Israel2 sites, 2 recruiting
- Recruiting
Rambam Health Care Campus
Haifa, Northern District, 3109601
- Recruiting
Schneider Children's Medical Center
Petah Tikva, Central District, 49202
Spain2 sites, 2 recruiting
- Recruiting
Hospital Universitario La Paz
Madrid, Madrid, Comunidad de, 28046
- Not yet recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
Greece1 site, 1 recruiting
- Not yet recruiting
Ippokrateio General Hospital of Thessaloniki
Thessaloniki, Kentrikí Makedonía, 546 42
Italy1 site, 1 recruiting
- Recruiting
Azienda Ospedaliera Universitaria Meyer IRCCS
Florence, Florence, 50139
About this study
Official title: A PHASE 2A, 2-PART, OPEN-LABEL, NON-RANDOMIZED, MULTICENTER, SINGLE AND MULTIPLE DOSE TRIAL TO EVALUATE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF AZTREONAM AND AVIBACTAM ± METRONIDAZOLE IN NEONATES AND INFANTS FROM BIRTH TO LESS THAN 9 MONTHS OF AGE WITH SUSPECTED OR CONFIRMED INFECTIONS DUE TO GRAM-NEGATIVE PATHOGENS REQUIRING INTRAVENOUS ANTIBIOTIC TREATMENT
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.
Read more
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.
Read the detailed description
This is a 2-part Phase 2a, non-randomized, multicenter, open-label, single and multi-dose study to assess pharmacokinetics (PK), safety, and tolerability of ATM-AVI in hospitalized neonates and infants aged birth, including preterm birth, to <9 months. A total of 48 participants will be enrolled in 4 age cohorts of 12 each, 6 Part A and 6 Part B. Part A will begin enrolling before Part B and no infant may participate in both parts. Cohort 1 will include full term infants age ≥13 weeks to <39 weeks and preterm infants postmenstrual age ≥50 weeks to <75 weeks. Cohort 2 will include full term infants age ≥28 weeks to <13 weeks and preterm infants postmenstrual age ≥40 weeks to <50 weeks and ≥28 days of age. Cohort 3 will include full term infants age birth to <28 days. Cohort 4 will include preterm infants age birth to <28 days or postmenstrual age <40 weeks.
Participants in Part A must be hospitalized and receiving intravenous antibiotic treatment for a suspected or confirmed bacterial infection. Participants will receive a single 3 hour intravenous infusion of ATM-AVI and have 3 ATM-AVI blood level assessments during and up to 5 hour after the infusion. Participants will be observed for 48 hours following the infusion to assess safety and toleration and will have a final follow-up safety assessment which may be conducted by telephone 4-5 weeks following the infusion. The single infusion of ATM-AVI is administered to assess the safety, tolerability, and pharmacokinetics of a single dose of ATM-AVI and is not intended as treatment for the bacterial infection. The total duration of study participation in Part A is expected to be 5 weeks through the end of the final safety follow-up.
Participants in Part B must be hospitalized with suspected or confirmed aerobic gram-negative bacterial infection requiring intravenous antibacterial therapy. Part B participants will receive multiple 3 hour intravenous infusions of ATM-AVI every 6 hour (8 hours for preterm infants) for 3-14 days as treatment for their bacterial infection and to assess ATM-AVI pharmacokinetics, safety, tolerability, and efficacy. Participants with complicated intra-abdominal infection (cIAI) will also receive intravenous metronidazole and all participants will have the option to receive other intravenous antibiotic treatment for gram-positive bacteria, as appropriate. Participants who have a good clinical response after 72 hours of intravenous ATM-AVI treatment may be switched to a different orally administered antibiotic, if clinically appropriate. Part B participants will have a total of 5 ATM-AVI blood level assessments over the first 2 or more days following the start of ATM-AVI infusions and will have their clinical response assessed at the End of Treatment (intravenous and oral, if applicable), and at a Test-of-Cure (TOC) evaluation 7 to 14 days after the last antibiotic treatment (intravenous or oral). A final safety assessment which may be conducted by telephone will occur 4-5 weeks after the last dose of ATM-AVI. The total duration of study participation in Part B is expected to be up to 7 weeks through the end of the final safety follow-up.
Additional safety monitoring will be provided by an independent external Data Monitoring Committee (DMC). Enrollment for the study will begin with Part A, single dose, cohorts 1-3. Part A Cohort 4 (preterm neonates) will commence enrollment after sponsor and DMC review of plasma drug levels and safety for a least 2 participants in Part A Cohort 3 and review of ATM-AVI safety and tolerability for all participants enrolled at that time. Enrollment in the multidose Part B cohorts will be delayed until preliminary information is obtained regarding ATM-AVI multidose safety, tolerability, and drug levels for the participants 9 months to 2 years of age in the separate ongoing ATM-AVI pediatric study C3601008 [NCT05639647].
- Conditions
- Gram-negative Bacterial Infection
- Being tested
- Part A: ATM-AVI Single Dose, Cohorts 1-4, Part B: Multiple-dose ATM-AVI, Cohorts 1-4
- Keywords
- gram-negative, aztreonam-avibactam, neonate, infant
- Medical subject headings
- Gram-Negative Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Part A: ATM-AVI Single Dose, Cohorts 1-4Drug
Single intravenous infusion of aztreonam-avibactam over 3 hours to assess pharmacokinetics, safety, and toleration.
Part B: Multiple-dose ATM-AVI, Cohorts 1-4Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Part A, Cohorts 1-4 | Experimental | Single dose pharmacokinetics. Receives: Drug: Part A: ATM-AVI Single Dose, Cohorts 1-4 |
| Part B, Cohorts 1-4 | Experimental | Multi-dose pharmacokinetics and treatment Receives: Drug: Part B: Multiple-dose ATM-AVI, Cohorts 1-4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Through study completion, up to Day 50
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2024
- Study start25 Sep 2024
- Primary completion25 Apr 2027 (estimated)
- Study completion25 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gram-negative Bacterial InfectionStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Non-randomized, 2-part with four age cohorts in each part
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06462235
- Sponsor's protocol ID
- C3601010
- Other IDs
- 2023-507757-15-01, 2023
- Acronym
- CHERISH
- Status last verified
- Oct 2026
- First submitted
- 28 May 2024
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.