Rifabutin plus polymyxin B combination for adult patients with hospital/ventilator‑associated pneumonia caused by carbapenem‑resistant Acinetobacter baumannii

The primary objective is to compare the efficacy of BV100 combined with low‑dose polymyxin B versus colistin plus high‑dose ampicillin/sulbactam in adult patients with hospital‑acquired or ventilator‑associated pneumonia caused by carbapenem‑resistant Acinetobacter baumannii‑calcoaceticus complex, thereby determining the relative therapeutic benefit of the investigational regimen.

Secondary objectives include:

• Evaluation of the overall safety profile of BV100 plus low‑dose polymyxin B.
• Assessment of efficacy of the BV100 regimen in all randomized participants in Part A.
• Assessment of efficacy of the BV100 regimen in the defined patient cohort of Part A.
• Assessment of efficacy of the BV100 regimen in the defined patient cohort of Part B.

The trial enrolled 322 adult patients, both male and female, aged 18 to 82 years, who were diagnosed with hospital‑acquired bacterial pneumonia (including ventilator‑associated pneumonia) attributable to carbapenem‑resistant Acinetobacter baumannii‑calcoaceticus complex. Participants were selected from intensive care settings based on a confirmed diagnosis requiring intravenous antibiotic therapy and a high probability that the infection was caused by the target pathogen, as determined by a rapid diagnostic test performed within the protocol‑specified time window. Inclusion required an Acute Physiology and Chronic Health Evaluation II score below 30 or a quick Sequential Organ Failure Assessment score of at least 2, and, for women of child‑bearing potential, a negative pregnancy test and agreement to use highly effective contraception throughout the study period. Patients who had received only a limited duration of prior active antimicrobial therapy or who demonstrated clinical failure after at least 48 hours of standard treatment were eligible, while those with contraindicating conditions such as pregnancy without appropriate contraception were excluded. The enrolled cohort represented a vulnerable population with severe respiratory infection requiring intensive medical management.

A prospective, multicenter, Phase 3, randomized, active‑controlled study will compare BV100 combined with low‑dose polymyxin B to colistin combined with high‑dose ampicillin/sulbactam in adult patients with hospital‑acquired bacterial pneumonia including ventilator‑associated bacterial pneumonia caused by carbapenem‑resistant Acinetobacter baumannii‑calcoaceticus complex. Eligible participants (aged 18–82 years) will undergo a screening visit to confirm diagnosis, obtain informed consent, and assess inclusion criteria such as APACHE II or qSOFA scores. After randomization, study drug will be administered intravenously and participants will be evaluated on Days 3, 5, 8, at the end of treatment, at the test‑of‑cure visit, and at the end‑of‑study visit, with safety assessments (adverse events, vital signs, laboratory tests, renal function, ECGs) performed at each visit. The primary efficacy endpoint is 28‑day all‑cause mortality in the CRABC m‑MITT population. Participants are expected to remain in the trial for approximately 28 days of treatment plus a follow‑up period up to the end‑of‑study assessment. Early termination may occur due to serious adverse events, withdrawal of consent, failure to isolate the target pathogen, or clinical deterioration indicating lack of therapeutic benefit. Recruitment is planned to begin on 10 June 2026 and conclude on 28 February 2028.

The comparator regimen includes ampicillin and β‑lactamase inhibitor (ampicillin sodium, sulbactam sodium, and lidocaine hydrochloride) supplied as pharmaceutical form PHF00231MIG. The medication is prepared for intravenous infusion and administered at a dose of 9 DF dosage form per the study dosing schedule.

The test arm incorporates polymyxin B sulfate, provided as powder for solution for infusion. The drug is reconstituted and delivered by intravenous infusion at a dose of 1 million IU per administration.

As a comparator, colistin is supplied in pharmaceutical form PHF00110MIG for intravenous infusion. The prescribed dose is 13.5 million IU per infusion.

The experimental component also includes rifabutin, formulated as a solution for infusion. It is administered intravenously at a dose of 600 mg per infusion.

All study medications are administered via intravenous infusion according to the protocol‑defined dosing schedule. Dosing times, infusion rates, and completion of each administration are recorded in the case report form, and adherence is monitored through infusion logs and periodic review of medication administration records.

Efficacy will be evaluated primarily by measuring 28‑day all‑cause mortality (ACM) in the CRABC m‑MITT population during Part A of the study. Secondary efficacy parameters include clinical cure rates at the test‑of‑cure (ToC) visit, as well as ACM at 28 days across the ITT, MITT and CRABC m‑MITT cohorts, and at 14 days in the MITT and CRABC m‑MITT groups. Additional secondary measures comprise clinical cure assessments on Days 3, 5, 8, at the end of treatment (EoT), ToC and end of study (EoS) in multiple analysis sets, and microbiological favorable assessments at the same time points in the MITT, m‑MITT and CRABC m‑MITT populations.

Clinical cure will be determined using predefined clinical criteria applied by investigators at each scheduled visit. Microbiological favorable assessment will be based on culture results and susceptibility testing performed in the study laboratory. Mortality data will be collected through patient follow‑up visits and review of medical records up to 28 days post‑randomization. All efficacy endpoints will be analyzed according to the appropriate population definitions (ITT, MITT, m‑MITT, CRABC m‑MITT, PP) using standard statistical methods for binary outcomes.