A Phase 2A, 2-Part, Open-Label, Non-Randomized, Multicenter, Single and Multiple DoseTrial to Evaluate Pharmacokinetics, Safety and Tolerability of Aztreonam and Avibactam ±Metronidazole in Neonates and Infants From Birth to Less Than 9 Months of Age WithSuspected or Confirmed Infections Due to Gram-Negative Pathogens Requiring IntravenousAntibiotic Treatment

Study on Safety and Effects of Investigational Antibiotic in Infants

A
Anna Elizabeth Thomas

Primary Investigator

Enrolling By Invitation
9 months or below
All
Phase 1/2
1 participants needed
1 Location

Brief description of study

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.

THIS STUDY IS ENROLLING BY INVITATION ONLY

Detailed description of study

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].

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Gram-negative Bacterial Infection
  • Age: 9 months or below
  • Gender: All

Inclusion Criteria

Participants must meet the following key inclusion criteria to be eligible for enrollment into the study:

  1. Hospitalized with age from birth <9 months, including preterm birth
  2. 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.
  3. 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:

  1. Received any other investigational medicinal product within the longer of 30 days or 5 half-lives before enrollment.
  2. 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.
  3. 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.
  4. 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.

Updated on 30 Jun 2025. Study ID: PNEO-PFIZER-ATM-AVI, 23615

This study investigates the safety and effects of an investigational medication for treating infections caused by gram-negative bacteria in newborns and infants. Gram-negative bacteria are a type of bacteria that can cause various infections and are known for their resistance to antibiotics. The investigational medication is a combination of two substances: aztreonam, which is an antibiotic, and avibactam, which helps prevent bacteria from becoming resistant to antibiotics.

Participants in this study will undergo different procedures depending on the part of the study they are in. In Part A, participants will receive a single intravenous infusion of the investigational medication and have their blood levels checked at different times to assess how the body absorbs and processes the medication. In Part B, participants will receive multiple infusions over several days and may also receive another antibiotic, metronidazole, if they have a specific type of infection. The study will also monitor safety and how well the medication works.

  • Who can participate: Infants from birth to less than 9 months old, including those born prematurely, who are hospitalized with suspected or confirmed bacterial infections are eligible. Participants must not have severe kidney issues or have received other investigational treatments recently.
  • Study details: Participants will receive either a single or multiple infusions of the investigational medication. In Part A, the focus is on assessing safety and drug levels with a single infusion. In Part B, participants receive multiple infusions as a treatment, with additional antibiotics if needed. A placebo is not used in this study.
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Interested in the study?

This study is accepting only persons who receive care at a certain clinic or doctor or who are part of an invited group. Questions about this study can be directed to the study team listed in the description or contact your doctor to see if you are eligible.

Accepting Referrals by Invitation Only