A study of BV100 plus low dose polymyxin B for treating hospital -acquired and ventilator-associated pneumonia caused by antibiotic resistant Acinetobacter bacteria

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bioversys S.A.S.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01], Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2026-06-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2025-524092-23-00

ClinicalTrials.gov

NCT07326540

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To compare the efficacy of BV100 plus low dose polymyxin B with colistin plus high dose ampicillin/sulbactam in patients with CRABC infections in Part A

Secondary objectives 4

1. To compare the efficacy of BV100 plus low dose polymyxin B with colistin plus high dose ampicillin/sulbactam in all randomized patients in Part A
2. To describe the overall safety profile of BV100 plus low-dose polymyxin B
3. To evaluate the efficacy of BV100 plus low dose polymyxin B in patients in Part A
4. To evaluate the efficacy of BV100 plus low dose polymyxin B in patients in Part B

Conditions and MedDRA coding

Hospital-acquired bacterial pneumonia including ventilator-associated bacterial pneumonia caused by carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Data obtained through this study may be provided to qualified researchers with an academic interest in the medical condition under study. Data shared will be coded. Approval of the request and execution of all applicable agreements (e.g., a data transfer or data sharing agreement) are prerequisites to sharing the data with the requesting party.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. (1) Provide written informed consent prior to any study related procedures not part of normal medical care. If permitted by local country and institution-specific guidelines, surrogate consent/use of a legally authorized representative may be provided. Alternatively, the decision can be made according to the procedure permitted by local law and institutional Standard Operating Procedures. If a patient regains consciousness while in the study and, per the Investigator’s judgment, the patient is able to read, assess, understand, and make his/her own decision to participate in the study, the patient may agree to continue participation. In such cases, the patient must be reconsented.
2. (2) Male or female patients, ≥ 18 and ≤ 82 years of age at the time of signing informed consent.
3. (3) A confirmed diagnosis of HABP or VABP requiring treatment with IV antibiotics in the judgment of the Investigator.
4. (4) High probability of a pneumonia (HABP or VABP) due to ABC as a single pathogen, or member of a polymicrobial infection based on evidence from RDT from a sample collected within a specified time period as per the protocol (CCI) prior to randomization, AND one of the following: (a) Has received no more than a specified number of hours as per the protocol (CCI) of potentially active antimicrobial treatment against CRABC prior to the first dose of study drug; OR (b) Is clinically failing prior treatment regimens (i.e., clinical deterioration or failure to improve after at least 48 hours of antibiotic treatment). Note: RDTs using an acceptable respiratory sample (PSB, BAL, mini BAL, ETA, or sputum) should be used to enable early detection of possible ABC pneumonia. A minimum amount in copies/mL (CCI) of ABC are required to consider RDT as positive. Patients can be randomized based on the results of the RDT while awaiting results of cultures from the local laboratory. However, if the respiratory sample does not grow ABC in the local microbiology laboratory culture, these patients will be withdrawn from the study drug treatment and treated at the Investigator’s discretion. Patients randomized in Part A based on positive RDT but subsequently with values below thresholds for ABC for the resulting quantitative or semi quantitative cultures can continue the study treatment at the discretion of the Investigator. Refer to the Microbiology Laboratory Manual for specifics.
5. (5) An Acute Physiology and Chronic Health Evaluation II (APACHE II) < 30 or quick Sequential Organ Failure Assessment (qSOFA) score ≥ 2 at Screening. Note: an APACHE II score or a qSOFA score that was calculated as part of standard of care within 24 hours of Screening may be used and does not need to be repeated.
6. (6) Women of childbearing potential (i.e., not post-menopausal or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test before randomization. Participating women of childbearing potential must be willing to consistently use one highly effective method of contraception (e.g., condom, combined oral contraceptive, implant, injectable, indwelling intrauterine device, or a vasectomized partner) from Screening until at least 30 days after administration of the last dose of study drug. Note: Women of childbearing potential who are on combined oral contraceptives only are required to use an additional (i.e. barrier) method of contraception from Screening until at least 30 days after administration of the last dose of study drug.
7. (7) Diagnosed with HABP or VABP as defined in detail in the Protocol.
8. (8) Part B will include patients with HABP or VABP who do not qualify for Part A. These patients should be considered for enrollment in Part B if they meet ANY of the following criteria, in addition to the general inclusion above: (1) Have an infection caused by CRABC organisms known to be resistant to colistin or polymyxin B (defined as MIC ≥ 4 mg/L by a non-agar-based method). (2) For known colistin- or polymyxin B-resistant infections, the following must be satisfied: (a) Have a known resistant infection based on evidence from culture and susceptibility testing by a non-agar-based method within a specified time period as per the protocol (CCI) prior to randomization, either alone or as a single organism of a polymicrobial infection; AND has received no more than a specified number of hours as per the protocol (CCI) of an antimicrobial agent to which the CRABC is susceptible prior to the first dose of study drug; OR (b) Have documented clinical evidence of failure (i.e., clinical deterioration or failure to improve that is attributable to CRABC) after at least a specified number of hours as per the protocol (CCI) of treatment with colistin or polymyxin B.

Exclusion criteria 24

1. (1) For Part A only, patients with an infection known to be resistant to colistin (defined as MIC ≥ 4 mg/L by a non-agar-based method), with a known intolerance to polymyxins, or taking any drug that prevents them from receiving polymyxins.
2. (5) Patients classified under futility of care, as determined by the medical team, indicating a lack of potential for benefit from intervention or patients who are permanent residents of long-term care facilities and have been assessed by the clinical team as receiving palliative or comfort-focused care.
3. (6) Sustained shock with persisting hypotension requiring vasopressors to maintain mean arterial pressure ≥ 65 mmHg (calculate mean arterial pressure = diastolic pressure plus 1/3 (systolic pressure minus diastolic pressure)) with patients requiring escalating vasopressor support to maintain adequate arterial pressure in conjunction with rising lactate. Examples for exceptions to exclusion criterion (6): (a) Patients sedated with propofol or requiring heavy sedation for whom their physician prescribed a low nonescalating dose of norepinephrine (< 1 µg/kg/min) to preserve adequate arterial pressure. (b) Patients receiving a weaning dose of noradrenaline < 1 µg/kg/min in the absence of hypotension or septic shock. (c) Patients receiving a low dose of norepinephrine (< 1 µg/kg/min) or equivalent to maintain the blood pressure after a ventilator parameter change.
4. (7) Diagnosis of ventilator-associated tracheobronchitis.
5. (13) Requirement at the time of randomization for any reason, or likely to require during the patient’s participation in the study (from randomization through the EoS Visit), for additional systemic Gram-negative antimicrobial therapy potentially active toward CRABC.
6. (14) Expected survival < 72 hours or a Do Not Resuscitate Order.
7. (15) Burns > 40% of total body surface area.
8. (16) Presence of neutropenia (absolute neutrophil count < 1500/mm3) obtained from a local laboratory at Screening, or anticipated neutropenia with absolute neutrophil count < 1500 cells/mm3.
9. (17) Severe renal disease defined as an estimated glomerular filtration rate (eGFR) as per Modification of Diet in Renal Disease (MDRD) formula (MDRD eGFR) < 30 mL/min/1.73 m2, or requirement for peritoneal dialysis, hemodialysis, hemofiltration, or a urine output < 20 mL/hour over a 24 hour period.
10. (18) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3× the upper limit of normal (ULN) AND total bilirubin > 2×ULN at Screening (using local laboratory values); or Child Pugh Class C in patients with chronic liver function impairment. Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis, hepatic cirrhosis, hepatic failure, chronic ascites, or hepatic encephalopathy. Note: Patients with AST or ALT up to 5×ULN are eligible if these elevations are acute and are documented as being directly related to the infectious process being treated.
11. (19) Investigator’s opinion of clinically significant ECG finding such as new ischemic changes, infarct, or ventricular arrhythmia with immediate potential for a fatal outcome, bradycardia not corrected by pacemaker or medication, or, prior to the current infection, a history of New York Heart Association Class IV cardiac failure defined as severe limitations – experiences symptoms even while at rest, mostly bedbound patients, within 1 year.
12. (8) Inability to provide proper respiratory specimens for culture. Respiratory samples from ETA or expectorated or induced sputum should show ≤ 10 squamous epithelial cells and ≥ 25 polymorphonuclear neutrophils per 100× field.
13. (20) Abnormal QT interval corrected for heart rate by Fridericia formula (QTcF): > 500 ms confirmed with repeat ECG.
14. (21) Stroke (ischemic or intracerebral hemorrhage) within 10 days prior to randomization or expected survival from stroke < 28 days or a Glasgow Coma Scale (GCS) score 3 with no hope of improvement.
15. (22) Women who are pregnant or nursing.
16. (23) Patients who are currently enrolled in or have not yet completed, in the last 30 days or 5 half lives, whichever is longer, another investigational device or drug study or those who are receiving other investigational agents.
17. (9) Received more than a specified number of hours as per the protocol (CCI) of potentially active treatment against CRABC prior to the first dose of study drug. Examples for exceptions to exclusion criterion (9): (a) Patient developed symptoms of VABP or HABP and/or a new infiltrate or positive blood culture while receiving the prior antibacterial regimen for reasons other than the current pneumonia; if the pneumonia occurred while the patient was receiving antibiotics as prophylaxis or for treatment of an unrelated infection, the antibacterial therapy will be considered ineffective irrespective of the susceptibility profile of the study qualifying pathogen; OR (b) Patient received systemic antibacterial therapy that does not cover CRABC; OR (c) Prior therapy with a nonabsorbed antibiotic therapy (e.g., oral vancomycin, metronidazole, or fidaxomicin) used for gut decontamination or to eradicate Clostridium difficile.
18. (12) Requirement for continuing treatment with probenecid, methotrexate, ganciclovir, valproic acid, or divalproex sodium during the study.
19. (10) Known or suspected allergy to polymyxin, rifabutin, colistin, ampicillin/sulbactam, meropenem or their excipients.
20. (11) Acute graft-versus-host disease (Grade ≥ 3).
21. (2) Evidence of active concurrent pneumonia requiring additional antimicrobial treatment caused by, e.g., Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, Pneumocystitis jiroveci, Aspergillus spp, respiratory syncytial virus, influenza and parainfluenza viruses, Middle East respiratory syndrome coronavirus, mycobacteria, mucormycosis. Note: If these organisms are identified but it is deemed by the Investigator that no treatment is warranted and their presence does not significantly change the prognosis of the patient, then the patient may be considered for this study.
22. (3) Any of the following health conditions: (a) Pulmonary disease that precludes evaluation of a therapeutic response (such as lung cancer resulting in bronchial obstruction or on the same side as the pneumonia, active tuberculosis, cystic fibrosis, granulomatous disease, fungal pulmonary infection, lung abscess, pleural empyema, post obstructive pneumonia, or known or suspected coronavirus disease 2019 infection without clinical improvement). Patients with known or suspected severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) infection are not allowed to be randomized in this study, unless the suspected A. baumannii pneumonia is diagnosed 7 days or more after the detection of SARS CoV 2. However, a patient who was previously polymerase chain reaction (PCR) positive for SARS CoV 2 and remains PCR positive for SARS CoV 2 at least 14 days after the first SARS CoV 2 PCR positive test may be included in the study. (b) Pleural empyema (exception: acceptable if drainage occurs within 24 hours of Screening and patient is expected to be treated in ≤ 14 days). (c) Solid organ transplant within 6 months prior to randomization. (d) Evidence of deep seated infection, e.g., Gram-negative osteomyelitis, or meningitis requiring prolonged therapy. If a deep-seated infection is drained and sanitized, it does not exclude the patient. (e) Acute infective endocarditis due to Gram-positive bacteria that requires urgent treatment/emergent indication of surgery (i.e., heart failure because of valvular insufficiency or septic shock), or patients in whom surgery is contraindicated due to prohibitive risk for surgery due to comorbidities. (f) Surgical wound infections requiring further surgical management e.g., wound closure, drain removal. (g) Peritonitis. (h) Irremovable implantable device or line thought to be the source of the ABC infection. (i) Known or suspected neuropathy or neuromuscular disease. (j) Human immunodeficiency virus infection. (k) Chronic immunosuppression due to drugs and/or underlying disease e.g., severe combined immunodeficiency, lupus, active chemotherapy, azathioprine; at the discretion of the Investigator.
23. (4) Bronchial obstruction or a history of post obstructive pneumonia (this does not exclude patients with pneumonia who have an underlying chronic obstructive pulmonary disease).
24. (24) Unable or not willing, in the opinion of the Investigator, to comply with all study protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 28-day ACM in the CRABC m-MITT Population in Part A

Secondary endpoints 4

1. Clinical cure at ToC in the CRABC m-MITT Population, 28-day ACM in the ITT and MITT Populations, 28-day ACM in the ITT, MITT, and CRABC m-MITT Populations in VABP patients only, 14-day ACM in the MITT and CRABC m-MITT Populations
2. Safety will be evaluated in the Safety Population through the assessment of the following: Adverse events, Vital signs (blood pressure, heart rate, and body temperature), Clinical laboratory evaluations (chemistry, hematology, and urinalysis), Concomitant medications, Renal function, Electrocardiograms
3. Clinical cure at Day 3, Day 5, Day 8, EoT, ToC, and EoS in the ITT, MITT, m-MITT, CRABC m-MITT, and PP Populations in Part A; Microbiological favorable assessment at Day 3, Day 5, Day 8, EoT, ToC, and EoS in the MITT, m-MITT, and CRABC m MITT Populations in Part A
4. 28-day ACM in the ITT, MITT, and CRABC m-MITT Populations in Part B; Clinical cure at Day 3, Day 5, Day 8, EoT, ToC, and EoS in the MITT, m-MITT, CRABC m-MITT, and PP Populations in Part B

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bioversys S.A.S.

Sponsor organisation

Bioversys S.A.S.

Address

1 Rue Du Professeur Calmette

City

Lille

Postcode

59800

Country

France

Scientific contact point

Organisation

Bioversys S.A.S.

Contact name

BioVersys Chief Development Officer

Public contact point

Organisation

Bioversys S.A.S.

Contact name

BioVersys Chief Development Officer

Third parties 2

Locations

2 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications