To Evaluate the Efficacy and Safety of Intravenous Imipenem/Cilastatin/XNW4107 in Comparison With Recarbrio in Adults With HABP /VABP

• Status: Not yet recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sinovent Pty Ltd.
• Treatments: Cilastatin; Imipenem; Relebactam

Criteria

Inclusion Criteria:

1. Patients willing and able to provide written informed consent or where consent is provided by legally authorized representatives.

2. Willing and able to comply with all study assessments and adhere to the protocol schedule.

3. Male or female patients ≥18 years on the day of signing informed consent.

4. Has HABP or VABP as defined below and requires treatment with IV antibiotic therapy.

5. All patients must fulfill at least 1 of the following clinical criteria at Screening:

• New onset or worsening of pulmonary symptoms or signs, such as cough, dyspnea, tachypnea, expectorated sputum production, or requirement for mechanical ventilation

• Hypoxemia

• 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

• New onset of or increase in suctioned respiratory secretions, demonstrating evidence of inflammation and absence of contamination.

6. All patients must have at least 1 of the following symptoms/signs/laboratory abnormalities at screening:

1. Documented fever

2. Hypothermia

3. Leukocytosis with a total peripheral white blood cell (WBC) count ≥10,000 cells/mm³

4. Leukopenia with total peripheral WBC count <4500 cells/mm³

5. Greater than 15% immature neutrophils noted on peripheral blood smear.

7. 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.

8. All patients must have a suspected Gram-negative infection involving the lower respiratory tract.

9. 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:

1. If a Gram stain from a respiratory sample shows only Gram-positive cocci.

2. Patients who have known or suspected community-acquired bacterial pneumonia, atypical pneumonia, viral pneumonia including COVID-19, or chemical pneumonia.

3. Patients who have HABP/VABP caused by an obstructive process, including lung cancer or other known obstruction.

4. 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.

5. Has a concurrent condition or infection that, in the investigator's judgment, would preclude evaluation of therapeutic response.

6. Patients who have central nervous system infection.

7. 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.

8. 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.

9. History of a seizure disorder.

10. Renal function at Screening as estimated glomerular filtrated rate <15 mL/min/1.73㎡, calculated using Modification of Diet in Renal Disease.

11. Patient is receiving hemodialysis or peritoneal dialysis or micro-dialysis or continuous venovenous hemofiltration or continuous venovenous hemodialysis.

12. Patient is anticipated to be treated with any of the following medications during the course of study therapy:

1. Valproic acid or divalproex sodium

2. Concomitant systemic (IV or oral) Gram-negative antibacterial agents in addition to those designated in the study treatment groups

3. Concomitant systemic (IV or oral) antifungal or antiviral therapy for the index infection of HABP/VABP.

13. Life expectancy is <3 days.

14. Patients in refractory septic shock, defined as persistent hypotension despite adequate fluid resuscitation and vasopressive therapy at the time of randomization.

15. 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.

16. History of active liver disease, cirrhosis.

17. Patients with an APACHE II score of >30.

18. 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.

19. A female who is pregnant or breastfeeding or has a positive pregnancy test at Screening.

20. 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.

21. Any other condition or prior therapy, which, in the opinion of the investigator, would make the patient unsuitable for this study.