Gram-negative Bacterial Infection Clinical Trial
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. 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.
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]. ;
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