This is a randomized, active-controlled, multicenter phase II clinical trial. The study aims to evaluate the efficacy, safety and tolerability of two different dosing regimens of ASK0912 for Injection compared with Polymyxin B Sulfate for Injection in adult patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP) caused by multidrug-resistant or carbapenem-resistant Gram-negative bacilli. Eligible subjects will be randomly assigned to one of three treatment groups: ASK0912 Regimen 1, ASK0912 Regimen 2, or Polymyxin B Sulfate active comparator group. Subjects will receive assigned intravenous study treatment for 7 to 14 days. The primary efficacy endpoints include clinical cure rate at the Test of Cure (TOC) visit and Day 28 all-cause mortality in the modified intent-to-treat (MITT) population. Safety assessments will be conducted throughout the study to monitor adverse events, laboratory parameters and other safety indicators.
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.
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.
Parallel
ASK0912 for Injection
DrugASK0912 for injection administered at a dose of 0.75 mg/kg every 12 hours
ASK0912 for Injection
DrugASK0912 for injection administered at a dose of 0.5 mg/kg every 8 hours
Polymyxin B Sulfate for Injection
DrugPolymyxin B Sulfate for Injection:Loading dose of 2.0-2.5 mg/kg; maintaining dose 1.25-1.5 mg/kg after 12 hours
Percentage of Participants Achieving Clinical Cure at Test of Cure (TOC) Visit in the Modified Intent to Treat (MITT) Population
Clinical cure was defined as all pretherapy signs and symptoms of the index infection have resolved or returned to preinfection status with no evidence of resurgence AND no additional antibiotic therapy was required for the index infection. The percentage of participants achieving clinical cure at TOC visit in the MITT population is presented.
Percentage of Participants With All-cause Mortality(ACM) Through Day 28 in the Modified Intent to Treat (MITT) Population
For each participant, survival status was assessed at Day 28 post-randomization and recorded on the electronic Case Report Form. The percentage of participants with all-cause mortality through Day 28 in the MITT population is presented.
Clinical cure rate
Clinical cure rate at the EOT visit in the MITT and micro-MITT populations
All-cause mortality
All-cause mortality at Day 14 in the MITT population
Microbiological success rate
Microbiological success rate at EOT and TOC visits in the micro-MITT populations
Composite clinical and microbiological cure rate
Composite clinical and microbiological cure rate at EOT and TOC visits in the micro-MITT populations
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