Evaluation of the Efficacy and Safety of Intravenous Imipenem/Cilastatin/XNW4107 in Comparison With Recarbrio in Adults With HABP /VABP (EudraCT no. 2022-000081-18)
Study Details
Study Description
Brief Summary
This is 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Imipenem/Cilastatin/XNW4107 Imipenem/Cilastatin 500mg/500mg in combination with XNW4107 250mg, Q6h (0.5h Infusion) |
Drug: Combination of Imipenem/Cilastatin and XNW4107
Imipenem/Cilastatin 500mg/500mg and XNW4107 250mg for Injection
|
| Active Comparator: Imipenem/Cilastatin/Relebactam Imipenem/Cilastatin/Relebactam 1.25g Q6h (0.5h Infusion) |
Drug: Imipenem/Cilastatin/Relebactam
Imipenem/Cilastatin/Relebactam 1.25 g for Injection
Other Names:
|
Outcome Measures
Primary Outcome Measures
- all-cause mortality rate [Up to Day 14]
The primary endpoint is the Day 14 all-cause mortality rate in the modified-intent-to-treat (MITT) population.
Secondary Outcome Measures
- all-cause mortality rate [Up to Day 28]
Day 28 all-cause mortality rate in the MITT population
- all-cause mortality rate [Up to Day 14 and Up to Day 28]
Day 14 and Day 28 all-cause mortality rate in the micro-MITT, extended micro-MITT, Clinically evaluable(CE), Microbiologically evaluable(ME) and Carbapenem-resistant-MITT(CR-MITT) populations
- clinical success [Day 4; EOT: from treatment day 7 up to day 15; TOC: Day 21[±2 days]; LFU: Day 28[±3 days]]
The proportion of patients with clinical success at Day 4, End of treatment(EOT), Test of cure(TOC) and Late follow-up(LFU) visits in the MITT, micro-MITT , extended micro-MITT, CE, ME, and CR-MITT populations
- microbiological success [EOT: from treatment day 7 up to day 15; TOC: Day 21[±2 days];]
The proportion of patients with microbiological success at EOT and TOC visits in the micro-MITT , extended micro-MITT, and ME populations
- microbiological success [EOT: from treatment day 7 up to day 15; TOC: Day 21[±2 days]; LFU: Day 28[±3 days]]
The proportion of patients with microbiological success at EOT, TOC and LFU visits in the CR-MITT population
- By-Pathogen microbiological success [EOT: from treatment day 7 up to day 15; TOC: Day 21[±2 days]; LFU: Day 28[±3 days]]
The proportion of patients with by-pathogen microbiological success at EOT, TOC, and LFU visits in the micro-MITT, extended micro-MITT, ME, and CR-MITT population
- Adverse events [Up to LFU: Day 28[±3 days]]
Incidence of all AEs, including SAEs
Other Outcome Measures
- Total number of days in hospital [Up to Day 28]
Total number of days in hospital within 28 days after randomization for MITT population
- Number of days in intensive care unit (ICU) [Up to Day 28]
Number of days in intensive care unit (ICU) through 28 days after randomization for MITT population
- Number of days on a ventilator and ventilator free days [Up to Day 28]
Number of days on a ventilator and ventilator free days through 28 days after randomization for the subgroup of VABP patients includingand ventilated-HABP in the MITT population.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients willing and able to provide written informed consent or where consent is provided by legally authorized representatives.
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Willing and able to comply with all study assessments and adhere to the protocol schedule.
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Male or female patients ≥18 years on the day of signing informed consent.
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Has HABP or VABP as defined below and requires treatment with IV antibiotic therapy.
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All patients must fulfill at least 1 of the following clinical criteria at Screening:
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New onset or worsening of pulmonary symptoms or signs, such as cough, dyspnea, tachypnea, expectorated sputum production, or requirement for mechanical ventilation
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Hypoxemia
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Need for acute changes in the ventilator support system to enhance oxygenation, as determined by worsening oxygenation or needed changes in the amount of positive end-expiratory pressure
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New onset of or increase in suctioned respiratory secretions, demonstrating evidence of inflammation and absence of contamination.
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All patients must have at least 1 of the following symptoms/signs/laboratory abnormalities at screening:
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Documented fever
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Hypothermia
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Leukocytosis with a total peripheral white blood cell (WBC) count ≥10,000 cells/mm³
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Leukopenia with total peripheral WBC count <4500 cells/mm³
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Greater than 15% immature neutrophils noted on peripheral blood smear.
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All patients must have a chest radiograph during Screening or have a previous chest radiograph within 48 hours prior to randomization showing the presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia.
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All patients must have a suspected Gram-negative infection involving the lower respiratory tract.
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Agree to allow any bacterial isolates obtained from protocol-required specimens related to the current infection to be provided to the Central Microbiology Reference Laboratory for study- related microbiological testing, long-term storage, and other future testing.
Exclusion Criteria:
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If a Gram stain from a respiratory sample shows only Gram-positive cocci.
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Patients who have known or suspected community-acquired bacterial pneumonia, atypical pneumonia, viral pneumonia including COVID-19, or chemical pneumonia.
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Patients who have HABP/VABP caused by an obstructive process, including lung cancer or other known obstruction.
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Have received effective systemic and inhaled Gram-negative antibacterial drug therapy for the index infection of HABP/VABP for a continuous duration of more than 24 hours during the previous 72 hours prior to randomization.
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Has a concurrent condition or infection that, in the investigator's judgment, would preclude evaluation of therapeutic response.
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Patients who have central nervous system infection.
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Documented presence of immunodeficiency or an immunocompromised condition including hematologic malignancy, bone marrow transplant, known history of human immunodeficiency virus infection with a CD4 count <200/mm³, or requiring frequent or prolonged use of systemic corticosteroids or other immunosuppressive drugs.
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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.
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History of a seizure disorder.
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Renal function at Screening as estimated glomerular filtrated rate <15 mL/min/1.73㎡, calculated using Modification of Diet in Renal Disease.
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Patient is receiving hemodialysis or peritoneal dialysis or micro-dialysis or continuous venovenous hemofiltration or continuous venovenous hemodialysis.
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Patient is anticipated to be treated with any of the following medications during the course of study therapy:
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Valproic acid or divalproex sodium
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Concomitant systemic (IV or oral) Gram-negative antibacterial agents in addition to those designated in the study treatment groups
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Concomitant systemic (IV or oral) antifungal or antiviral therapy for the index infection of HABP/VABP.
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Life expectancy is <3 days.
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Patients in refractory septic shock, defined as persistent hypotension despite adequate fluid resuscitation and vasopressive therapy at the time of randomization.
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Patients with 1 or more of the following laboratory abnormalities in baseline specimens: aspartate aminotransferase, alanine aminotransferase >3 × the upper limit of normal (ULN), total bilirubin level >2 × ULN (except for isolated hyperbilirubinemia due to known Gilbert's disease), neutrophils <500 cells/mm³, platelet count <40,000/mm³.
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History of active liver disease, cirrhosis.
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Patients with an APACHE II score of >30.
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Female patients of childbearing potential, who are unable or unwilling to use a highly effective method of birth control during the study and for at least 30 days following the last dose of study medication.
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A female who is pregnant or breastfeeding or has a positive pregnancy test at Screening.
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Patient is participating in any clinical study of any investigational medication (i.e., non-licensed medication) during the 30 days prior to randomization. COVID-19 vaccines that are given under emergency use authorization are not considered investigational agents.
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Any other condition or prior therapy, which, in the opinion of the investigator, would make the patient unsuitable for this study.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Sinovent Pty Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- XNW4107-302