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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Hospital Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia

Intervention / Treatment
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* Drug: Combination of Imipenem/Cilastatin and XNW4107
* Drug: Imipenem/Cilastatin/Relebactam


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imipenem/Cilastatin/XNW4107<br>Imipenem/Cilastatin 500mg/500mg in combination with XNW4107 250mg, Q6h (0.5h Infusion) | Drug: Combination of Imipenem/Cilastatin and XNW4107<br>* Imipenem/Cilastatin 500mg/500mg and XNW4107 250mg for Injection<br>|
| Active Comparator: Imipenem/Cilastatin/Relebactam<br>Imipenem/Cilastatin/Relebactam 1.25g Q6h (0.5h Infusion) | Drug: Imipenem/Cilastatin/Relebactam<br>* Imipenem/Cilastatin/Relebactam 1.25 g for Injection<br>* Other names: Recarbrio;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Day 14 all-cause mortality rate | all-cause mortality rate at day 14 | Up to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Day 28 all-cause mortality rate | all-cause mortality rate at day 28 | Up to Day 28 | 
| The proportion of subjects with clinical success at Day 4 | The proportion of subjects with clinical success at Day 4 | Day 4 | 
| The proportion of subjects with clinical success at EOT | The proportion of subjects with clinical success at EOT | at end of treatment (EOT) of each patient, up to 14 days | 
| The proportion of subjects with clinical success at TOC | The proportion of subjects with clinical success at TOC | at test-of-cure (TOC), up to 14 days | 
| The proportion of subjects with clinical success at LFU | The proportion of subjects with clinical success at LFU | at Late Follow-up (LFU), up to 31 days | 
| The proportion of subjects with overall success at EOT | The proportion of subjects with overall success at EOT | at end of treatment (EOT), up to 14 days | 
| The proportion of subjects with overall success at TOC | The proportion of subjects with overall success at TOC | at test of cure (TOC), up to 14 days | 
| The proportion of subjects with overall success at LFU | The proportion of subjects with overall success at LFU | at Late Follow-up (LFU), up to 31 days |