Hospital-acquired Bacterial Pneumonia (HABP), Ventilator-associated Bacterial Pneumonia (VABP)
Conditions
Keywords
Hospital-Acquired Bacterial Pneumonia, Ventilator-Associated Bacterial Pneumonia, Polymyxin B, ASK0912
Brief summary
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.
Interventions
DRUGASK0912 for Injection
ASK0912 for injection administered at a dose of 0.75 mg/kg every 12 hours
DRUGPolymyxin B Sulfate for Injection
Polymyxin B Sulfate for Injection:Loading dose of 2.0-2.5 mg/kg; maintaining dose 1.25-1.5 mg/kg after 12 hours
Sponsors
Jiangsu Aosaikang Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Clinical Cure at Test of Cure (TOC) Visit in the Modified Intent to Treat (MITT) Population | Up to approximately 28 days | 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 | Up to approximately 28 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical cure rate | Up to approximately 14 days | Clinical cure rate at the EOT visit in the MITT and micro-MITT populations |
| All-cause mortality | 14 days post-randomization | All-cause mortality at Day 14 in the MITT population |
| Microbiological success rate | 28 days post-randomization | Microbiological success rate at EOT and TOC visits in the micro-MITT populations |
| Composite clinical and microbiological cure rate | 28 days post-randomization | Composite clinical and microbiological cure rate at EOT and TOC visits in the micro-MITT populations |
| Early clinical response rate | Day 3 post-dose | Clinical response rate at OTX1 visit in the ITT and MITT populations |
Countries
China
Contacts
CONTACTJiangsu Aosaikang Study Director
Outcome results
None listed