ASK0912 Versus Polymyxin B for Injection in Adults With Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia

Inclusion criteria

• 1. Aged 18-75 years on the day of informed consent signature;
• 2. Require intravenous antibiotic therapy for hospital-acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP).
• 3. At least one clinical sign or symptom of HABP/VABP.
• 4. At least one laboratory abnormality of HABP/VABP.
• 5. Chest imaging at screening demonstrating new or progressive infiltrates consistent with pneumonia.
• 6. APACHE II score ≤ 30.
• 7. Appropriate lower respiratory tract specimen obtained at screening for Gram stain and bacterial culture.
• 8. Subjects receiving HABP/VABP-active antibiotics within 72h pre-enrollment may enroll if ≤24h therapy, or ≥48h with persistent/worsening HABP/VABP signs/symptoms at screening.
• 9. Women of childbearing potential must have a negative pregnancy test (serum or urine) prior to enrollment.
• 10. Male subjects must use highly effective contraception throughout the study period.

Exclusion criteria

• 1. Subjects with known allergy to polymyxins or carbapenems, regardless of the severity of the reaction; or subjects with a severe hypersensitivity reaction to any other β-lactam agent.
• 2. Subjects who have received any investigational product within 3 months prior to enrollment, or subjects who have previously participated in this clinical study.
• 3. Has a baseline lower respiratory tract specimen Gram stain that shows the presence of Gram-positive cocci only.
• 4. Known or suspected pneumonia caused by Mycoplasma, Chlamydia, Legionella, fungi, parasites, viruses, or chemical etiologies (including gastric aspiration, inhalation injury).Additionally, subjects with confirmed or suspected community-acquired bacterial pneumonia (CABP) are excluded.
• 5. Presence of underlying pulmonary conditions that may interfere with efficacy assessment, such as pulmonary tuberculosis, lung abscess, empyema, obstructive pneumonia, granulomatous disease, recent pulmonary embolism, moderate-to-severe bronchiectasis, severe chronic obstructive pulmonary disease, bronchial obstruction, idiopathic interstitial pneumonia, etc.
• 6. Presence of other active infections that may interfere with efficacy assessment, or bacterial infectious foci requiring concomitant treatment with antibacterial agents prohibited by the study protocol, such as invasive fungal infection, endocarditis, central nervous system infection (e.g., meningitis, brain abscess, post-shunt infection), septic arthritis requiring vancomycin, etc.
• 7. Severe cardiac disorders, including severe arrhythmia, significant myocardial ischemia, congestive heart failure classified as NYHA Class III-IV.
• 8. Subjects with liver cirrhosis classified as Child-Pugh Class C.
• 9. Subjects with documented immunodeficiency or impaired immune function, including HIV infection, hematological malignancies, bone marrow transplantation, etc.; or subjects receiving immunosuppressive therapy, including immunosuppressants, chemotherapeutic agents, drugs for prevention of transplant rejection, and corticosteroids (prednisone ≥ 20 mg/day for more than 14 days).
• 10. Presence of any one of the following abnormalities: aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 5 × upper limit of normal (ULN); AST and/or ALT > 3 × ULN accompanied by total bilirubin > 1.5 × ULN; creatinine clearance < 80 mL/min (calculated using the Cockcroft-Gault formula); absolute neutrophil count < 1 × 10⁹/L; platelet count < 60 × 10⁹/L.
• 11. Subjects with a history or evidence of severe renal disease, or receiving hemodialysis or peritoneal dialysis.
• 12. Subjects presenting with shock.
• 13. Subjects scheduled to undergo major surgery during the study period.
• 14. Subjects with a known history of epilepsy or neuromuscular junction disorders such as myasthenia gravis.
• 15. Subjects with any past or current disease, treatment, laboratory abnormality, or other condition that, in the investigator's opinion, may compromise the quality of study data or increase treatment risks during the study, e.g., subjects requiring valproic acid therapy during the study.
• 16. Subjects with any psychiatric or psychological disorder judged by the investigator to potentially increase trial risks, impair protocol compliance, or hinder study completion, such as recent (within the past 12 months) or active suicidal ideation/behavior.
• 17. Subjects judged by the investigator on clinical assessment to be at risk of death within the 7-14-day treatment phase despite adequate antibiotic therapy for pneumonia.
• 18. Female subjects who are breastfeeding or plan to breastfeed prior to the end of the study.
• 19. Any other conditions rendering the subject unsuitable for participation in this study as determined by the investigator.