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Completed

NCT Number: NCT05204563

Imipenem/Cilastatin-XNW4107 Versus Imipenem/Cilastatin/Relebactam for Treatment of Participants With Bacterial Pneumonia (XNW4107-302, REITAB-2)

This study aims to compare treatment with Imipenem/Cilastatin-XNW4107 (IMI-XNW4107) with imipenem/cilastatin/relebactam (IMI/REL) in participants with hospital-acquired or ventilator-associated bacterial pneumonia (HABP or VAPB, respectively). The primary hypothesis is that IMI-XNW4107 is non-inferior to IMI/REL in all-cause mortality.

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Key information

Conditions

Hospital Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

CHU de Nice, Nice, Alpes Maritimes, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Has HABP or VABP as defined below and requires treatment with IV antibiotic therapy. Fulfills clinical criteria, with onset of criteria occurring after more than 48 hours of hospitalization or within 7 days after discharge from a hospital (for HABP); or at least 48 hours after mechanical ventilation (for VABP)
  • Fulfills clinical criteria with symptoms or signs of cough, expectorated sputum production, dyspnea, worsening oxygenation, increase in respiratory secretions, fever/ hypothermia..
  • Fulfills laboratory test criteria with Leukocytosis/ Leukocytosis/ increase in immature neutrophils
  • Fulfill radiograph criteria with presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia in X-ray/ Chest CT.
  • Female subjects of childbearing potential, who are willing to birth control during the study and for at least 30 days following the last dose of study medication. Male subjects with female sexual partners of childbearing potential are eligible for inclusion if they agree to use birth control for 90 days following the last dose of study medication. Male subjects must agree not to donate sperm

Exclusion criteria

  • Gram stain from a respiratory sample shows only Gram-positive cocci.
  • Have known or suspected community-acquired bacterial pneumonia, atypical pneumonia, viral pneumonia including Coronavirus disease, or chemical pneumonia.
  • Have HABP/VABP caused by an obstructive process, including lung cancer or other known obstruction.
  • Have received effective antibacterial drug therapy for the index infection of HABP/VABP for more than 24 hours during the previous 72 hours .
  • Have central nervous system infection.
  • Documented presence of immunodeficiency or an immunocompromised condition
  • Documented or severe hypersensitivity or previous severe adverse drug reaction, especially to any beta-lactam antibiotics, or any of the excipients used in the study drug formulations.
  • History of a seizure disorder requiring ongoing treatment with anti-convulsive therapy or prior treatment with anti-convulsive therapy within the last 3 years.
  • eGFR <15 mL/min/1.73㎡.
  • Patient is receiving hemodialysis or peritoneal dialysis.
  • Anticipated to be treated with any of Valproic acid or divalproex sodium, concomitant systemic Gram-negative antibacterial agents, or concomitant systemic antifungal or antiviral therapy for the index infection of HABP/VABP.
  • Life expectancy is <3 days.
  • Patients in refractory septic shock
  • Patients with 1 or more of laboratory abnormalities in baseline specimens.
  • History of active liver disease or cirrhosis.
  • APACHE II score of >30.
  • A female who is pregnant or breastfeeding or has a positive pregnancy test at Screening.

Treatment and study plan

Combination of Imipenem/Cilastatin and XNW4107

Drug

Imipenem/Cilastatin 500mg/500mg and XNW4107 250mg for Injection

Imipenem/Cilastatin/Relebactam

Drug

Imipenem/Cilastatin/Relebactam 1.25 g for Injection

Other names: Recarbrio

Primary outcomes

  1. Day 14 All-cause Mortality Rate

    Time frame: Day 14

    The all-cause mortality rate at Day 14 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 14.

Secondary outcomes

  1. Day 28 All-cause Mortality Rate

    Time frame: Day 28

    The all-cause mortality rate at Day 28 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 28.

  2. Day 14 and Day 28 All-cause Mortality Rate in the Micro-MITT Population

    Time frame: Day 14, Day 28

    The all-cause mortality rate at Day 14 and Day 28 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 14 and Day 28.

  3. Day 14 and Day 28 All-cause Mortality Rate in the Extended Micro-MITT

    Time frame: Day 14, Day 28

    The all-cause mortality rate at Day 14 and Day 28 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 14 and Day 28.

  4. Day 14 and Day 28 All-cause Mortality Rate in the Clinically Evaluable (CE) Population

    Time frame: Day 14, Day 28

    The all-cause mortality rate at Day 14 and Day 28 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 14 and Day 28.

  5. Day 14 and Day 28 All-cause Mortality Rate in the Microbiologically Evaluable (ME) Population

    Time frame: Day 14, Day 28

    The all-cause mortality rate at Day 14 and Day 28 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 14 and Day 28.

  6. Day 14 and Day 28 All-cause Mortality Rate in the Carbapenem-resistant MITT (CR-MITT) Population

    Time frame: Day 14, Day 28

    The all-cause mortality rate at Day 14 and Day 28 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 14 and Day 28.

  7. The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the MITT Population

    Time frame: Day 4, end of treatment (EOT) (up to Day 14), Test-of-Cure (TOC) (Day 21), and Late Follow-up (LFU) (Day 28)

    Clinical success was defined as: For Day 4 visit: a participant was alive with resolution or improvement in at least 1 baseline sign/symptom AND no worsening of any baseline signs/symptoms AND no development of new signs/symptoms of pneumonia requiring the initiation of a non-study antibacterial therapy for the index infection. For end of treatment (EOT) or test-of-cure (TOC) visits: a participant was alive with complete resolution or significant improvement of signs and symptoms that were present at baseline and no new signs/symptoms of pneumonia, such that no further antibacterial therapy is necessary. For LFU, Clinical success at TOC with sustained resolution or marked improvement of baseline signs and symptoms of pneumonia during TOC and LFU without antimicrobial therapy (pneumonia).

  8. The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the Micro-MITT Population

    Time frame: Day 4, EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

    Clinical success was defined as: For Day 4 visit: a participant was alive with resolution or improvement in at least 1 baseline sign/symptom AND no worsening of any baseline signs/symptoms AND no development of new signs/symptoms of pneumonia requiring the initiation of a non-study antibacterial therapy for the index infection. For EOT or TOC visits: a participant was alive with complete resolution or significant improvement of signs and symptoms that were present at baseline and no new signs/symptoms of pneumonia, such that no further antibacterial therapy is necessary. For LFU, Clinical success at TOC with sustained resolution or marked improvement of baseline signs and symptoms of pneumonia during TOC and LFU without antimicrobial therapy (pneumonia).

  9. The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the Extended Micro-MITT

    Time frame: Day 4, EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

    Clinical success was defined as: For Day 4 visit: a participant was alive with resolution or improvement in at least 1 baseline sign/symptom AND no worsening of any baseline signs/symptoms AND no development of new signs/symptoms of pneumonia requiring the initiation of a non-study antibacterial therapy for the index infection. For EOT or TOC visits: a participant was alive with complete resolution or significant improvement of signs and symptoms that were present at baseline and no new signs/symptoms of pneumonia, such that no further antibacterial therapy is necessary. For LFU, Clinical success at TOC with sustained resolution or marked improvement of baseline signs and symptoms of pneumonia during TOC and LFU without antimicrobial therapy (pneumonia).

  10. The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the CE Population

    Time frame: Day 4, end of treatment (EOT) (up to Day 14), Test-of-Cure (TOC) (Day 21), and Late Follow-up (LFU) (Day 28)

    Clinical success was defined as: For Day 4 visit: a participant was alive with resolution or improvement in at least 1 baseline sign/symptom AND no worsening of any baseline signs/symptoms AND no development of new signs/symptoms of pneumonia requiring the initiation of a non-study antibacterial therapy for the index infection. For EOT or TOC visits: a participant was alive with complete resolution or significant improvement of signs and symptoms that were present at baseline and no new signs/symptoms of pneumonia, such that no further antibacterial therapy is necessary. For LFU, Clinical success at TOC with sustained resolution or marked improvement of baseline signs and symptoms of pneumonia during TOC and LFU without antimicrobial therapy (pneumonia).

  11. The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the ME Population

    Time frame: Day 4, end of treatment (EOT) (up to Day 14), Test-of-Cure (TOC) (Day 21), and Late Follow-up (LFU) (Day 28)

    Clinical success was defined as: For Day 4 visit: a participant was alive with resolution or improvement in at least 1 baseline sign/symptom AND no worsening of any baseline signs/symptoms AND no development of new signs/symptoms of pneumonia requiring the initiation of a non-study antibacterial therapy for the index infection. For EOT or TOC visits: a participant was alive with complete resolution or significant improvement of signs and symptoms that were present at baseline and no new signs/symptoms of pneumonia, such that no further antibacterial therapy is necessary. For LFU, Clinical success at TOC with sustained resolution or marked improvement of baseline signs and symptoms of pneumonia during TOC and LFU without antimicrobial therapy (pneumonia).

  12. The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the CR-MITT Population

    Time frame: Day 4, end of treatment (EOT) (up to Day 14), Test-of-Cure (TOC) (Day 21), and Late Follow-up (LFU) (Day 28)

    Clinical success was defined as: For Day 4 visit: a participant was alive with resolution or improvement in at least 1 baseline sign/symptom AND no worsening of any baseline signs/symptoms AND no development of new signs/symptoms of pneumonia requiring the initiation of a non-study antibacterial therapy for the index infection. For EOT or TOC visits: a participant was alive with complete resolution or significant improvement of signs and symptoms that were present at baseline and no new signs/symptoms of pneumonia, such that no further antibacterial therapy is necessary. For LFU, Clinical success at TOC with sustained resolution or marked improvement of baseline signs and symptoms of pneumonia during TOC and LFU without antimicrobial therapy (pneumonia).

  13. The Percentage of Participants With Microbiological Success in the Micro-MITT Population

    Time frame: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

    Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

  14. The Percentage of Participants With Microbiological Success in the Extended Micro-MITT Population

    Time frame: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

    Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

  15. The Percentage of Participants With Microbiological Success in the CR-MITT Population

    Time frame: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

    Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

  16. The Percentage of Participants With Microbiological Success in the ME Population

    Time frame: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

    Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

  17. The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population

    Time frame: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

    Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

  18. The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population

    Time frame: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

    Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

  19. The Percentage of Participants With Microbiological Success by Pathogen in the ME Population

    Time frame: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

    Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

  20. The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population

    Time frame: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

    Microbiological success was defined as: • Eradication: Absence of the baseline Gram-negative pathogen from an appropriate clinical specimen • Presumed eradication: Absence of appropriate post-baseline culture material in a participant, but judged to be a clinical success.

  21. The Percentage of Participants With Overall Success in the Micro-MITT Population

    Time frame: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

    Overall success was defined as clinical success and microbiological success at the visits of EOT or TOC, or sustained success for clinical outcome and microbiological success at the visit of LFU. Microbiological success included eradication or presumed eradication.

  22. The Percentage of Participants With Overall Success in the Extended Micro-MITT Population

    Time frame: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

    Overall success was defined as clinical success and microbiological success at the visits of EOT or TOC, or sustained success for clinical outcome and microbiological success at the visit of LFU. Microbiological success included eradication or presumed eradication.

  23. The Percentage of Participants With Overall Success in the ME Population

    Time frame: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

    Overall success was defined as clinical success and microbiological success at the visits of EOT or TOC, or sustained success for clinical outcome and microbiological success at the visit of LFU. Microbiological success included eradication or presumed eradication.

  24. The Percentage of Participants With Overall Success in the CR-MITT Population

    Time frame: EOT (up to Day 14), TOC (Day 21), and LFU (Day 28)

    Overall success was defined as clinical success and microbiological success at the visits of EOT or TOC, or sustained success for clinical outcome and microbiological success at the visit of LFU. Microbiological success included eradication or presumed eradication.

  25. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Time frame: Day 1 to Day 28

    A TEAE was defined as any untoward medical occurrence after first dose associated with the use of a drug in humans, whether or not considered drug-related. An SAE was defined as any adverse event (AE) occurring at any dose that met one or more of the following criteria: resulted in death, was life-threatening, required participant hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability or incapacity, a congenital anomaly or birth defect or an important medical event.

  26. Blood XNW4107, Imipenem, and Cilastatin Concentrations

    Time frame: Predose, 5-25 minutes post-dose, and 2-3 hours post-dose on Day 4, 5, or 6

    Blood samples were taken for analysis of XNW4107, imipenem, and cilastatin concentrations. The data at each time point was calculated as an average across Days 4, 5 and 6.

Sponsors and collaborators

Lead sponsor

Evopoint Biosciences Inc.

Industry

Registry information

Official study title

A Multicenter, Randomized, Double-Blind, Comparative, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous Imipenem/Cilastatin/XNW4107 in Comparison With Imipenem/Cilastatin/Relebactam in Adults With Hospital-Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia (EudraCT no. 2022-000081-18) (EUCTR no. 2022-501952-27-00) (IND no. 146614)

Acronym: REITAB-2

Important dates

Study start
2022
Primary completion
2024
Study completion
2024
First posted
Jan 24, 2022
Registry last updated
Nov 6, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.