This is a two-part study, with Part A being the randomized, controlled portion of the study in patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP) suspected or confirmed to be due to carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRABC). Part B is the single-group portion of the study and includes patients with HABP or VABP with CRABC infections that are resistant to or have failed colistin/polymyxin B treatment.
This is a Phase 3, randomized, active-controlled two-part parallel-group study to evaluate the efficacy and safety of BV100 plus low-dose polymyxin B in patients with HABP or VABP suspected or confirmed to be due to CRABC infection. Eligible patients who provide informed consent will be enrolled in the study and will have pretreatment blood and infection site-specific samples collected and submitted to a local laboratory. The overall study design consists of two parts in which patients will be recruited in parallel. Part A is the pivotal, randomized, comparative portion of the study, focusing on patients with suspected or confirmed CRABC HABP or VABP. Part A of the study will employ a partially blinded design. Site personnel directly involved in patient care and treatment administration will be unblinded to treatment assignment; however, access to treatment allocation information, including data potentially revealing assigned treatment arm, will be restricted for Sponsor study personnel. No personnel employed at the Sponsor will have access to the data, maintaining blinding for all Sponsor employees. Project management and oversight and medical query management will be conducted by unblinded external providers or vendors. The Central Adjudication Committee (CAC) will be the blinded assessor. Part B is a prospective multicenter, open-label, nonrandomized, additional single group to evaluate the efficacy and safety of BV100 plus low-dose polymyxin B in patients with HABP or VABP due to CRABC known to be resistant to colistin or polymyxin B prior to study entry and patients where colistin or polymyxin B regimen has failed prior to study entry. Approximately 25 patients are expected to be enrolled in Part B. Patients randomized to either group of Part A cannot be transferred to Part B.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
248
300 mg BV100 nfused over 2 hours every 12 hours (q12h).Treatment for 7 days up to 14 days if clinically indicated.
50 mg polymyxin B infused over 2 hours every 12 hours (q12h).Treatment for 7 days up to 14 days if clinically indicated.
Colistin (4,500,000 units infused over 1 hour every 12 hours (q12h), after an initial loading dose of 9,000,000 units infused over 1 hour).Treatment for 7 days up to 14 days if clinically indicated.
High dose ampicillin/sulbactam (6 g/3 g IV over 4 hours q8h).Treatment for 7 days up to 14 days if clinically indicated.
meropenem infused over 1 hour every 8 hours (q8h).Treatment for 7 days up to 14 days if clinically indicated.
The proportion of patients with All-Cause Mortality in CRABC m-MITT Population
The primary efficacy endpoint for the study is 28-day all-cause mortality (ACM) in the CRABC Microbiological Modified Intention-to-Treat (CRABC m-MITT) population in Part A.
Time frame: Day 28
Proportion of Patients with clinical cure at ToC in CRABC m-MITT Population
Clinical cure status (cure, failure, indeterminate) will be assessed at the ToC in CRABC m-MITT Population in Part A
Time frame: 7 days after end of treatment
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