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    Clinical Trial Results:
    A multicenter, open-label, randomized, active-controlled, Phase 2 study to evaluate the pharmacokinetics, efficacy, and safety of intravenous BV100 combined with polymyxin B versus best available therapy in adult patients with ventilator-associated bacterial pneumonia suspected or confirmed to be due to carbapenem-resistant Acinetobacter baumannii

    Summary
    EudraCT number
    		 2022-002856-37
    Trial protocol
    		 HU  
    Global end of trial date
    26 Sep 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Feb 2026
    First version publication date
    28 Feb 2026
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    BV100-006
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 NCT number: NCT05685615
    Sponsors
    Sponsor organisation name
    BioVersys SAS
    Sponsor organisation address
    1 rue du Pr Calmette/3 rue du Pr Laguesse, Lille, France, 59000
    Public contact
    Lead Project Manager, PSI CRO Hungary LLc, +36 15556755, tamas.szirak@psi-cro.com
    Scientific contact
    Lead Project Manager, PSI CRO Hungary LLc, +36 15556755, tamas.szirak@psi-cro.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    24 Mar 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Sep 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To investigate the PK properties of BV100 co-administered with polymyxin B during 7 to 14 days of treatment in patients with ventilator-associated bacterial pneumonia (VABP) due to suspected or documented CRAB infection.
    Protection of trial subjects
    This trial was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki, the Council for International Organizations of Medical Sciences international ethical guidelines, and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) E6(R2) Guidelines. In addition, all local laws and regulatory requirements were followed, in particular, those affording greater protection to the safety of trial patients. A DSMB was appointed to this trial to make recommendations to the Sponsor regarding the modification, continuance, or stopping of the trial based on assessments of safety or for efficacy based futility.
    Background therapy
    		 None.
    Evidence for comparator
    		 Polymyxin B is not a substrate of any important hepatic drug metabolizing enzymes or transporters and is unlikely to be associated with any drug-drug interactions with BV100. Thus, the combination of polymyxin B and BV100 was not expected to result in AEs not directly attributable to either polymyxin B or BV100. The dose of polymyxin B used in this trial followed the international consensus guidelines for the optimal use of polymyxins. The anti-Acinetobacter antibiotics that represent BAT in the control group depended on the local susceptibility pattern of CRAB isolates. These antibiotics correspond to the commonly used antibiotics with anti-Acinetobacter activity. For patients in Part A randomized to best available therapy (BAT) and for patients in Part B, the BATs were to be determined according to country and individual sites. The authorized anti-Acinetobacter antibiotic was to be administered according to the local site practice.
    Actual start date of recruitment
    27 Apr 2023
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Georgia: 28
    Country: Number of subjects enrolled
    Greece: 11
    Country: Number of subjects enrolled
    Hungary: 2
    Worldwide total number of subjects
    41
    EEA total number of subjects
    13
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    15
    From 65 to 84 years
    26
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 72 patients were screened and 41 were enrolled across 11 sites in Georgia, Greece, and Hungary. Of the 41 patients enrolled, 2 patients were not treated (1 patient in the BAT group and 1 patient in the BV100 300 mg + BAT [Part B] group were randomized by mistake). First Patient First Visit (date of informed consent) was on 27 April 2023.

    Pre-assignment
    Screening details
    		 Male and female patients ≥ 18 and ≤ 80 years of age diagnosed with VABP suspected/confirmed due to CRAB. Patients were eligible if they had BMI of < 40 kg/m2, were hospitalized ≥ 48 hours, intubated and receiving mechanical ventilation ≥ 48 hours at the time of randomization, and had clinical and radiological findings to support diagnosis of VABP.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 BV100 200 mg + Polymyxin B (Part A)
    Arm description
    		 Patients received multiple IV doses of BV100 200 mg + polymyxin B on Day 1 up to Day 14.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BV100
    Investigational medicinal product code
    Other name
    Rifabutin
    Pharmaceutical forms
    Concentrate and solvent for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    BV100 200 mg administered every 12 hours (± 1 hour) from Day 1 up to Day 14 (120-minute infusions [± 10 min]). In Part A, the polymyxin B infusion was to be administered first (60 min ± 10 min), followed immediately with the BV100 infusion (120 min ± 10 min).

    Investigational medicinal product name
    Polymyxin B
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Polymyxin B administered every 12 hours (± 1 hour) from Day 1 up to Day 14 (60-minute infusions [± 10 min]). The recommended dose of polymyxin B used in this trial followed the International Consensus Guidelines for the optimal use of polymyxins (Tsuji et al; 2019): Loading dose (Day 1) = 2.0-2.5 mg/kg* (equivalent to 20 000-25 000 IU/kg). Maintenance doses (q12h) = 1.25-1.5 mg/kg* (equivalent to 12 500-15 000 IU/kg). In Part A, the polymyxin B infusion was to be administered first (60 min ± 10 min), followed immediately with the BV100 infusion (120 min ± 10 min). *Based on total body weight (TBW). Maximum dose was 2.5 mg/kg/day (25 000 IU/kg). The total daily dose was not to exceed 200 mg/day given as 100 mg q12h, 1h infusions.

    Arm title
    		 BV100 300 mg + Polymyxin B (Part A)
    Arm description
    		 Patients received multiple IV doses of BV100 300 mg + polymyxin B on Day 1 up to Day 14.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BV100
    Investigational medicinal product code
    Other name
    Rifabutin
    Pharmaceutical forms
    Powder and solvent for concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    BV100 300 mg administered every 12 hours (± 1 hour) from Day 1 up to Day 14 (120-minute infusions [± 10 min]). In Part A, the polymyxin B infusion was to be administered first (60 min ± 10 min), followed immediately with the BV100 infusion (120 min ± 10 min).

    Investigational medicinal product name
    Polymyxin B
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Polymyxin B administered every 12 hours (± 1 hour) from Day 1 up to Day 14 (60-minute infusions [± 10 min]). The recommended dose of polymyxin B used in this trial followed the International Consensus Guidelines for the optimal use of polymyxins (Tsuji et al; 2019): Loading dose (Day 1) = 2.0-2.5 mg/kg [1] (equivalent to 20 000-25 000 IU/kg). Maintenance doses (q12h) = 1.25-1.5 mg/kg [1] (equivalent to 12 500-15 000 IU/kg). In Part A, the polymyxin B infusion was to be administered first (60 min ± 10 min), followed immediately with the BV100 infusion (120 min ± 10 min). [1] Based on total body weight (TBW). Maximum dose was 2.5 mg/kg/day (25 000 IU/kg). The total daily dose was not to exceed 200 mg/day given as 100 mg q12h, 1h infusions.

    Arm title
    		 BAT (Part A)
    Arm description
    		 Patients received multiple doses of BAT on Day 1 up to Day 14.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    BAT
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Not assigned
    Routes of administration
    Infusion
    Dosage and administration details
    The BATs were to be determined according to country and individual sites and administered according to the local site practice.

    Arm title
    		 BV100 300 mg + BAT (Part B)
    Arm description
    		 Patients received multiple IV doses of BV100 300 mg + BAT on Day 1 up to Day 14.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BV100
    Investigational medicinal product code
    Other name
    Rifabutin
    Pharmaceutical forms
    Powder and solvent for concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    BV100 300 mg administered every 12 hours (± 1 hour) from Day 1 up to Day 14 (120-minute infusions [± 10 min]). In Part B, the BAT was to be administered first, followed immediately with the BV100 infusion.

    Investigational medicinal product name
    BAT
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Not assigned
    Routes of administration
    Infusion , Inhalation use
    Dosage and administration details
    The BATs were determined according to country and individual sites and were to be the same treatment received as before entering the trial but could change with treatment failure, at the discretion of the Investigator. In Part B, the BAT was to be administered first, followed immediately with the BV100 infusion.

    Number of subjects in period 1
    		BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Started
    10
    11
    11
    9
    Treated
    10
    11
    10
    8
    Completed
    9
    6
    4
    4
    Not completed
    1
    5
    7
    5
         Death
    1
    5
    6
    4
         Protocol deviation
    -
    -
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    BV100 200 mg + Polymyxin B (Part A)
    Reporting group description
    		 Patients received multiple IV doses of BV100 200 mg + polymyxin B on Day 1 up to Day 14.

    Reporting group title
    BV100 300 mg + Polymyxin B (Part A)
    Reporting group description
    		 Patients received multiple IV doses of BV100 300 mg + polymyxin B on Day 1 up to Day 14.

    Reporting group title
    BAT (Part A)
    Reporting group description
    		 Patients received multiple doses of BAT on Day 1 up to Day 14.

    Reporting group title
    BV100 300 mg + BAT (Part B)
    Reporting group description
    		 Patients received multiple IV doses of BV100 300 mg + BAT on Day 1 up to Day 14.

    Reporting group values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B) Total
    Number of subjects
    		 10 11 11 9 41
    Age categorical
    Units: Subjects
    Age continuous
    Age data are presented for the ITT population. Patients were between 31 and 79 years of age (mean 65.6 years).
    Units: years
        arithmetic mean (standard deviation)
    		 67.9 ( 8.62 ) 63.6 ( 10.44 ) 62.9 ( 16.10 ) 68.7 ( 10.17 ) -
    Gender categorical
    Gender data are presented for the ITT population. Most patients (65.9%) were male.
    Units: Subjects
        Female
    		 5 3 4 2 14
        Male
    		 5 8 7 7 27
    Race
    Race data are presented for the ITT population. All patients (100%) were White.
    Units: Subjects
        White
    		 10 11 11 9 41
        American Indian or Alaska Native
    		 0 0 0 0 0
        Black or African American
    		 0 0 0 0 0
        Asian
    		 0 0 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Not Reported
    		 0 0 0 0 0
        Other
    		 0 0 0 0 0
    Ethnicity
    Ethnicity data are presented for the ITT population. All patients (100%) were not Hispanic or Latino.
    Units: Subjects
        Hispanic or Latino
    		 0 0 0 0 0
        Not Hispanic or Latino
    		 10 11 11 9 41
        Not Reported
    		 0 0 0 0 0
    Country
    Country data are presented for the ITT population. Twenty-eight patients (68.3%) were enrolled from Georgia, 11 patients (26.8%) from Greece, and 2 patients (4.9%) from Hungary. All patients (100%) in the BAT group were from Georgia.
    Units: Subjects
        Georgia
    		 7 10 11 0 28
        Greece
    		 2 0 0 9 11
        Hungary
    		 1 1 0 0 2
    Childbearing Potential
    Childbearing potential percentages are based on the number of female patients. Childbearing data are presented for the ITT population. All female patients (100%) were post-menopausal and not of childbearing potential.
    Units: Subjects
        Yes
    		 0 0 0 0 0
        No
    		 5 3 4 2 14
        Not counted (male)
    		 5 8 7 7 27
    Days in the ICU prior to randomization
    ICU data are presented for the ITT population. Prior to randomization, more than half of patients (26 patients; 63.4%) had been in the ICU for 5 to 14 days.
    Units: Subjects
        <5
    		 1 2 5 0 8
        5-14
    		 8 8 4 6 26
        >14
    		 1 1 2 3 7
    eGFR (mL/min/1.73m2) at Screening
    eGFR data are presented for the ITT population. Two patients were randomized and/or enrolled by mistake, did not receive treatment, and did not have the eGFR assessment done by the central laboratory. The eGFR values at Screening were similar across all ranges: 24.4% had an eGFR < 60 mL/min/1.73m2, 24.4% had an eGFR ≥ 60 and < 90 mL/min/1.73m2, 19.5% had an eGFR ≥ 90 and ≤ 120 mL/min/1.73m2, and 24.4% had an eGFR > 120 mL/min/1.73m2.
    Units: Subjects
        <60
    		 3 2 2 3 10
        ≥60 and <90
    		 1 5 2 2 10
        ≥90 and ≤120
    		 2 3 3 0 8
        >120
    		 4 1 3 2 10
        Not done
    		 0 0 1 2 3
    Glasgow Coma Score (GCS) Neurologic Score
    GCS data are presented for the micro-ITT population. Most patients had a GCS score of ≤ 7. Four patients (10.3%) had a GCS score of 12.
    Units: Subjects
        0 points
    		 1 0 0 2 3
        1 point
    		 0 1 0 2 3
        4 points
    		 1 2 1 1 5
        5 points
    		 0 0 4 1 5
        6 points
    		 1 2 3 0 6
        7 points
    		 5 2 1 0 8
        8 points
    		 1 0 1 0 2
        9 points
    		 0 0 0 1 1
        10 points
    		 0 1 0 0 1
        11 points
    		 1 0 0 0 1
        12 points
    		 0 3 0 1 4
        Excluded from population
    		 0 0 1 1 2
    VABP Diagnosis Details: Time Since VABP Diagnosis
    VABP diagnosis details are presented for the micro-ITT population. The mean (standard deviation [SD]) time since VABP diagnosis: 2.4 (3.68) days.
    Units: Days
        arithmetic mean (standard deviation)
    		 1.4 ( 0.52 ) 2.5 ( 2.54 ) 1.1 ( 0.32 ) 5.1 ( 7.16 ) -
    Total APACHE II Score
    Total APACHE II score data are presented for the micro-ITT population. The mean (SD) total APACHE II score was 16.1 (4.36).
    Units: Score
        arithmetic mean (standard deviation)
    		 15.7 ( 2.58 ) 17.4 ( 5.20 ) 15.1 ( 3.60 ) 15.9 ( 5.94 ) -

    End points

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    End points reporting groups
    Reporting group title
    BV100 200 mg + Polymyxin B (Part A)
    Reporting group description
    		 Patients received multiple IV doses of BV100 200 mg + polymyxin B on Day 1 up to Day 14.

    Reporting group title
    BV100 300 mg + Polymyxin B (Part A)
    Reporting group description
    		 Patients received multiple IV doses of BV100 300 mg + polymyxin B on Day 1 up to Day 14.

    Reporting group title
    BAT (Part A)
    Reporting group description
    		 Patients received multiple doses of BAT on Day 1 up to Day 14.

    Reporting group title
    BV100 300 mg + BAT (Part B)
    Reporting group description
    		 Patients received multiple IV doses of BV100 300 mg + BAT on Day 1 up to Day 14.

    Subject analysis set title
    Intention-to-Treat (ITT) Population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT Population includes all patients randomized (Part A) and assigned (Part B), even if the patient did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. The ITT analyses used the treatment as randomized/assigned. The ITT population included all 41 (100%) enrolled patients (10 patients in the BV100 200 mg + polymyxin B group, 11 patients in the BV100 300 mg + polymyxin B group, 11 patients in the BAT group, and 9 patients in the BV100 300 mg + BAT [Part B] group).

    Subject analysis set title
    Microbiological ITT (micro-ITT) Population
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    The micro-ITT Population includes all patients in the ITT Population with (i) a Baseline RDT positive for A. baumannii, irrespective of the culture result, (ii) surveillance culture positive for A. baumannii, or (iii) a quantitative culture from a respiratory specimen or blood culture obtained within up to 36 hours prior to randomization (Part A) or assignment (Part B), positive for A. baumannii, regardless of its susceptibility to trial drug and who received at least 1 dose of trial treatment. Patients were analyzed according to the treatment as randomized/assigned. The micro-ITT and Safety populations were identical and each comprised a total of 39 patients (95.1%) overall, with 2 patients excluded from these populations (1 patient in the BAT group and 1 patient in the BV100 300 mg + BAT [Part B] group) due to not receiving at least 1 dose of trial treatment.

    Subject analysis set title
    Carbapenem-resistant MITT (micro-CRMITT)
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    The micro-CRMITT population includes all patients in the micro-ITT population with a quantitative culture from a respiratory specimen or blood culture obtained within up to 36 hours prior to randomization (Part A) or assignment (Part B), positive for CRAB, regardless of susceptibility to trial drug. Patients were analyzed according to the treatment as randomized/assigned. All patients with a suitable respiratory specimen who met the criteria for inclusion in the micro-CRMITT population had CRAB. The micro-CRMITT population comprised a total of 26 patients (63.4%) overall, including 9 patients (90.0%) in the BV100 200 mg + polymyxin B group, 7 patients (63.6%) in the BV100 300 mg + polymyxin B group, and 10 patients (90.9%) in the BAT group. No patients from the BV100 300 mg + BAT [Part B] group were included in the micro-CRMITT population.

    Subject analysis set title
    Safety Population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The Safety Population includes all patients from the ITT Population who received at least 1 dose of trial treatment (not counting BAT received prior to randomization) and had at least 1 post-baseline safety assessment. Patients were analyzed according to the actual treatment received. The Safety and micro-ITT populations were identical and each comprised a total of 39 patients (95.1%) overall, with 2 patients excluded from these populations (1 patient in the BAT group and 1 patient in the BV100 300 mg + BAT [Part B] group) due to not receiving at least 1 dose of trial treatment.

    Subject analysis set title
    Pharmacokinetic (PK) Population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The PK Population includes all patients in the Safety Population for whom at least 1 BV100 post-dose sample for PK analysis was available. The PK population comprised a total of 29 patients (70.7%) overall, including 10 patients (100%) in the BV100 200 mg + polymyxin B group, 11 patients (100%) in the BV100 300 mg + polymyxin B group, and 8 patients (88.9%) in the BV100 300 mg + BAT (Part B) group. Two patients were excluded due to not receiving at least 1 dose of trial treatment.

    Primary: Rifabutin Cmax

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    End point title
    		 Rifabutin Cmax [1]
    End point description
    Maximum observed plasma concentration (Cmax) for rifabutin. Plasma concentrations: Rifabutin and DMI concentrations above the lower limit of quantification (LLOQ) were quantified for most patients around 5 minutes post-infusion on Day 1 and pre-dose on Day 4. 25-O-desacetyl-rifabutin concentrations above the LLOQ were quantified for most patients around 1-2 hours post-infusion on Day 1 and pre-dose on Day 4. All PK data are presented for the PK population.
    End point type
    Primary
    End point timeframe
    PK blood sampling: Days 1 and 4: prior to first BV100 infusion, 5 min, 30 min, and 1, 2, 4, 8, and 12 hours post-infusion. Day 2: prior to first BV100 infusion. Days 5 and 9: prior to first BV100 infusion, 5 min post-infusion (if still on trial drugs).
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: All analyses were descriptive in nature and no formal statistical comparisons of data from different arms or trial parts were done.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10 [2]
    11 [3]
    0 [4]
    7 [5]
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Day 1
    689.0 ( 79.6 )
    1099 ( 108.0 )
    ( )
    705.5 ( 43.9 )
        Day 4
    1187 ( 71.9 )
    1306 ( 98.2 )
    ( )
    1431 ( 34.0 )
    Notes
    [2] - Patients analyzed: Day 1 = 10; Day 4 = 9
    [3] - Patients analyzed: Day 1 = 11; Day 4 = 11
    [4] - Patients did not receive BV100
    [5] - Patients analyzed: Day 1 = 7; Day 4 = 6
    No statistical analyses for this end point

    Primary: Rifabutin tmax

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    End point title
    		 Rifabutin tmax [6]
    End point description
    Time of occurrence of Cmax (tmax) for rifabutin.
    End point type
    Primary
    End point timeframe
    PK blood sampling: Days 1 and 4: prior to first BV100 infusion, 5 min, 30 min, and 1, 2, 4, 8, and 12 hours post-infusion. Day 2: prior to first BV100 infusion. Days 5 and 9: prior to first BV100 infusion, 5 min post-infusion (if still on trial drugs).
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: All analyses were descriptive in nature and no formal statistical comparisons of data from different arms or trial parts were done.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10 [7]
    11 [8]
    0 [9]
    7 [10]
    Units: hours
    median (full range (min-max))
        Day 1
    1.58 (0.08 to 4.02)
    1.00 (0.10 to 12.00)
    ( to )
    1.00 (0.08 to 2.02)
        Day 4
    2.00 (0.50 to 12.00)
    1.00 (0.08 to 12.00)
    ( to )
    1.00 (0.07 to 2.00)
    Notes
    [7] - Patients analyzed: Day 1 = 10; Day 4 = 9
    [8] - Patients analyzed: Day 1 = 11; Day 4 = 11
    [9] - Patients did not receive BV100
    [10] - Patients analyzed: Day 1 = 7 Day 4 = 6
    No statistical analyses for this end point

    Primary: Rifabutin AUC0-12

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    End point title
    		 Rifabutin AUC0-12 [11]
    End point description
    Area under the concentration-time curve from dosing (time 0) to 12h (AUC0-12) for rifabutin.
    End point type
    Primary
    End point timeframe
    PK blood sampling: Days 1 and 4: prior to first BV100 infusion, 5 min, 30 min, and 1, 2, 4, 8, and 12 hours post-infusion. Day 2: prior to first BV100 infusion. Days 5 and 9: prior to first BV100 infusion, 5 min post-infusion (if still on trial drugs).
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: All analyses were descriptive in nature and no formal statistical comparisons of data from different arms or trial parts were done.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    6 [12]
    9 [13]
    0 [14]
    4 [15]
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        Day 1
    2857 ( 45.3 )
    3791 ( 64.3 )
    ( )
    4565 ( 21.3 )
        Day 4
    6012 ( 44.2 )
    5921 ( 43.6 )
    ( )
    8357 ( 50.8 )
    Notes
    [12] - Patients analyzed: Day 1 = 6; Day 4 = 9
    [13] - Patients analyzed: Day 1 = 9; Day 4 = 8
    [14] - Patients did not receive BV100
    [15] - Patients analyzed: Day 1 = 4; Day 4 = 4
    No statistical analyses for this end point

    Primary: 25-O-desacetyl-rifabutin Cmax

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    End point title
    		 25-O-desacetyl-rifabutin Cmax [16]
    End point description
    Maximum observed plasma concentration (Cmax) for 25-O-desacetyl-rifabutin.
    End point type
    Primary
    End point timeframe
    PK blood sampling: Days 1 and 4: prior to first BV100 infusion, 5 min, 30 min, and 1, 2, 4, 8, and 12 hours post-infusion. Day 2: prior to first BV100 infusion. Days 5 and 9: prior to first BV100 infusion, 5 min post-infusion (if still on trial drugs).
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: All analyses were descriptive in nature and no formal statistical comparisons of data from different arms or trial parts were done.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    9 [17]
    9 [18]
    0 [19]
    7 [20]
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Day 1
    17.71 ( 78.3 )
    20.50 ( 97.9 )
    ( )
    22.94 ( 39.7 )
        Day 4
    25.33 ( 128.6 )
    28.03 ( 93.8 )
    ( )
    28.33 ( 80.0 )
    Notes
    [17] - Patients analyzed: Day 1 = 9; Day 4 = 10
    [18] - Patients analyzed: Day 1 = 9; Day 4 = 10
    [19] - Patients did not receive BV100
    [20] - Patients analyzed: Day 1 = 7; Day 4 = 6
    No statistical analyses for this end point

    Primary: 25-O-desacetyl-rifabutin tmax

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    End point title
    		 25-O-desacetyl-rifabutin tmax [21]
    End point description
    Time of occurrence of Cmax (tmax) for 25-O-desacetyl-rifabutin.
    End point type
    Primary
    End point timeframe
    PK blood sampling: Days 1 and 4: prior to first BV100 infusion, 5 min, 30 min, and 1, 2, 4, 8, and 12 hours post-infusion. Day 2: prior to first BV100 infusion. Days 5 and 9: prior to first BV100 infusion, 5 min post-infusion (if still on trial drugs).
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: All analyses were descriptive in nature and no formal statistical comparisons of data from different arms or trial parts were done.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    9 [22]
    9 [23]
    0 [24]
    7 [25]
    Units: hours
    median (full range (min-max))
        Day 1
    4.00 (1.00 to 11.92)
    2.02 (1.00 to 11.95)
    ( to )
    4.00 (1.03 to 11.98)
        Day 4
    2.02 (0.50 to 12.00)
    2.00 (0.00 to 12.00)
    ( to )
    2.01 (0.98 to 4.08)
    Notes
    [22] - Patients analyzed: Day 1 = 9; Day 4 = 10
    [23] - Patients analyzed: Day 1 = 9; Day 4 = 10
    [24] - Patients did not receive BV100
    [25] - Patients analyzed: Day 1 = 7; Day 4 = 6
    No statistical analyses for this end point

    Primary: 25-O-desacetyl-rifabutin: AUC0-12

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    End point title
    		 25-O-desacetyl-rifabutin: AUC0-12 [26]
    End point description
    Area under the concentration-time curve from dosing (time 0) to 12h (AUC0-12) for 25-O-desacetyl-rifabutin.
    End point type
    Primary
    End point timeframe
    Days 1 and 4: prior to first BV100 infusion, 5 min, 30 min, and 1, 2, 4, 8, and 12 hours post-infusion. Day 2: prior to first BV100 infusion. Days 5 and 9: prior to first BV100 infusion, 5 min post-infusion (if still on trial drugs).
    Notes
    [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: All analyses were descriptive in nature and no formal statistical comparisons of data from different arms or trial parts were done.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    4 [27]
    4 [28]
    0 [29]
    1 [30]
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        Day 1
    198.3 ( 35.4 )
    232.6 ( 56.7 )
    ( )
    142.6 ( 99999 )
        Day 4
    220.9 ( 106.5 )
    178.8 ( 81.5 )
    ( )
    292.8 ( 60.5 )
    Notes
    [27] - Patients analyzed: Day 1 = 4; Day 4 = 8
    [28] - Patients analyzed: Day 1 = 4; Day 4 = 7
    [29] - Patients did not receive BV100
    [30] - Patients analyzed: Day 1 = 1; Day 4 = 4. '99999' = CV not calculated as only 1 patient was evaluable
    No statistical analyses for this end point

    Primary: DMI Cmax

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    End point title
    		 DMI Cmax [31]
    End point description
    Maximum observed plasma concentration (Cmax) for DMI.
    End point type
    Primary
    End point timeframe
    PK blood sampling: Days 1 and 4: prior to first BV100 infusion, 5 min, 30 min, and 1, 2, 4, 8, and 12 hours post-infusion. Day 2: prior to first BV100 infusion. Days 5 and 9: prior to first BV100 infusion, 5 min post-infusion (if still on trial drugs).
    Notes
    [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: All analyses were descriptive in nature and no formal statistical comparisons of data from different arms or trial parts were done.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10 [32]
    11 [33]
    0 [34]
    7 [35]
    Units: µg/mL
    geometric mean (geometric coefficient of variation)
        Day 1
    12.62 ( 29.7 )
    14.32 ( 49.9 )
    ( )
    20.51 ( 37.7 )
        Day 4
    21.70 ( 40.2 )
    22.19 ( 36.5 )
    ( )
    48.74 ( 23.7 )
    Notes
    [32] - Patients analyzed: Day 1 = 10; Day 4 = 9
    [33] - Patients analyzed: Day 1 = 11; Day 4 = 11
    [34] - Patients did not receive BV100
    [35] - Patients analyzed: Day 1 = 7; Day 4 = 6
    No statistical analyses for this end point

    Primary: DMI tmax

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    End point title
    		 DMI tmax [36]
    End point description
    Time of occurrence of Cmax (tmax) for DMI.
    End point type
    Primary
    End point timeframe
    PK blood sampling: Days 1 and 4: prior to first BV100 infusion, 5 min, 30 min, and 1, 2, 4, 8, and 12 hours post-infusion. Day 2: prior to first BV100 infusion. Days 5 and 9: prior to first BV100 infusion, 5 min post-infusion (if still on trial drugs).
    Notes
    [36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: All analyses were descriptive in nature and no formal statistical comparisons of data from different arms or trial parts were done.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10 [37]
    11 [38]
    0 [39]
    7 [40]
    Units: hours
    median (full range (min-max))
        Day 1
    2.00 (0.47 to 4.02)
    2.00 (0.10 to 12.00)
    ( to )
    2.00 (0.08 to 4.00)
        Day 4
    2.00 (0.10 to 12.00)
    2.00 (0.50 to 12.00)
    ( to )
    1.51 (0.98 to 2.08)
    Notes
    [37] - Patients analyzed: Day 1 = 10; Day 4 = 9
    [38] - Patients analyzed: Day 1 = 11; Day 4 = 11
    [39] - Patients did not receive BV100
    [40] - Patients analyzed: Day 1 = 7; Day 4 = 6
    No statistical analyses for this end point

    Primary: DMI AUC0-12

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    End point title
    		 DMI AUC0-12 [41]
    End point description
    Area under the concentration-time curve from dosing (time 0) to 12h (AUC0-12) for DMI.
    End point type
    Primary
    End point timeframe
    PK blood sampling: Days 1 and 4: prior to first BV100 infusion, 5 min, 30 min, and 1, 2, 4, 8, and 12 hours post-infusion. Day 2: prior to first BV100 infusion. Days 5 and 9: prior to first BV100 infusion, 5 min post-infusion (if still on trial drugs).
    Notes
    [41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: All analyses were descriptive in nature and no formal statistical comparisons of data from different arms or trial parts were done.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    6 [42]
    9 [43]
    0 [44]
    4 [45]
    Units: h*µg/mL
    geometric mean (geometric coefficient of variation)
        Day 1
    89.48 ( 39.3 )
    99.96 ( 38.6 )
    ( )
    162.6 ( 15.6 )
        Day 4
    181.0 ( 50.5 )
    178.7 ( 48.9 )
    ( )
    460.8 ( 36.8 )
    Notes
    [42] - Patients analyzed: Day 1 = 6; Day 4 = 9
    [43] - Patients analyzed: Day 1 = 9; Day 4 = 8
    [44] - Patients did not receive BV100
    [45] - Patients analyzed: Day 1 = 4; Day 4 = 4
    No statistical analyses for this end point

    Secondary: ACM rates 14 and 28 days after randomization

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    End point title
    		 ACM rates 14 and 28 days after randomization [46]
    End point description
    The incidence of ACM within 14 and 28 days after randomization was obtained by collecting the survival status through 23:59 (24-hour clock) on Day 14 and Day 28 (EoS Visit) as either alive or dead. ACM rates are presented for the micro-CRMITT population. In Part A, the BV100 200 mg + polymyxin B group had the lowest ACM rates at both Day 14 (11.1%) and Day 28 (11.1%). A low ACM rate at Day 14 also occurred in the BV100 300 mg + polymyxin B group (14.3%) but was notably increased at Day 28 (42.9%). The BAT group had the highest ACM rates at both Day 14 (40.0%) and Day 28 (60.0%). Overall, ACM rates increased across all treatment groups from Day 14 (23.1%) to Day 28 (38.5%). There were no deaths attributed to trial treatment.
    End point type
    Secondary
    End point timeframe
    All-cause mortality (ACM) rates at 14 and 28 days, counted as the calendar days from first exposure to treatment.
    Notes
    [46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There were no patients in the BV100 300 mg + BAT (Part B) group for the population being reported for this endpoint (micro-CRMITT population).
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A)
    Number of subjects analysed
    9 [47]
    7 [48]
    10 [49]
    Units: percentage
    number (confidence interval 95%)
        ACM rate at Day 14
    11.1 (0.28 to 48.25)
    14.3 (0.36 to 57.87)
    40.0 (12.16 to 73.76)
        ACM rate at Day 28
    11.1 (0.28 to 48.25)
    42.9 (9.90 to 81.59)
    60.0 (26.24 to 87.84)
    Notes
    [47] - Number of deaths: Day 14 = 1, Day 28 = 1
    [48] - Number of deaths: Day 14 = 1, Day 28 = 3
    [49] - Number of deaths: Day 14 = 4, Day 28 = 6
    No statistical analyses for this end point

    Secondary: Clinical cure status at EoT

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    End point title
    		 Clinical cure status at EoT [50]
    End point description
    Clinical Cure data at EoT are presented for the micro-CRMITT population. At EoT, clinical cure was achieved in 18 patients (69.2%) overall. Clinical cure rates were greater in the BV100 300 mg + polymyxin B group (6 patients; 85.7%) and the BV100 200 mg + polymyxin B group (7 patients; 77.8%), compared to the BAT group (5 patients; 50.0%). The highest rate of clinical failure at EoT occurred in the BAT group (5 patients; 50.0%).
    End point type
    Secondary
    End point timeframe
    Clinical cure status (cure, failure, indeterminate) assessed by the Investigator at the End of Treatment (EoT) and Test of Cure (ToC) Visits.
    Notes
    [50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There were no patients in the BV100 300 mg + BAT group for the population being reported for this endpoint (micro-CRMITT population).
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A)
    Number of subjects analysed
    9 [51]
    7 [52]
    10 [53]
    Units: subjects
        Clinical cure
    7
    6
    5
        Clinical failure
    2
    1
    5
        Indeterminate
    0
    0
    0
    Notes
    [51] - Percentages: Clinical cure = 77.8%; Clinical failure = 22.2%; Indeterminate = 0%
    [52] - Percentages: Clinical cure = 85.7%; Clinical failure = 14.3%; Indeterminate = 0%
    [53] - Percentages: Clinical cure = 50.0%; Clinical failure = 50.0%; Indeterminate = 0%
    No statistical analyses for this end point

    Secondary: Clinical cure status at ToC

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    End point title
    		 Clinical cure status at ToC [54]
    End point description
    Clinical Cure data at ToC are presented for the micro-CRMITT population. At ToC, clinical cure was achieved in 15 patients (57.7%) overall. Clinical cure rates remained high and unchanged (from EoT) for the BV100 300 mg + polymyxin B group (6 patients; 85.7%). For the BV100 200 mg + polymyxin B group, a slight decrease in clinical cure rate occurred (6 patients; 66.7%), and the BAT group had a notable decrease (3 patients; 30.0%). The clinical cure rate in the combined BV100 + polymyxin B treatment groups was 75.0% (12 patients). The highest rate of clinical failure at ToC occurred in the BAT group (7 patients; 70.0%).
    End point type
    Secondary
    End point timeframe
    Clinical cure status (cure, failure, indeterminate) assessed by the Investigator at the EoT and ToC Visits.
    Notes
    [54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There were no patients in the BV100 300 mg + BAT B (Part B) group for the population being reported for this endpoint (micro-CRMITT population).
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A)
    Number of subjects analysed
    9 [55]
    7 [56]
    10 [57]
    Units: subjects
        Clinical cure
    6
    6
    3
        Clinical failure
    3
    1
    7
        Indeterminate
    0
    0
    0
    Notes
    [55] - Percentages: Clinical cure = 66.7%; Clinical failure = 33.3%; Indeterminate = 0%
    [56] - Percentages: Clinical cure = 85.7%; Clinical failure = 14.3%; Indeterminate = 0%
    [57] - Percentages: Clinical cure = 30.0%; Clinical failure = 70.0%; Indeterminate = 0%
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in PaO2/FiO2 Ratio

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    End point title
    		 Change from Baseline in PaO2/FiO2 Ratio
    End point description
    Changes from Baseline in PaO2/FiO2 ratio are presented for the micro-ITT population. At Baseline, most patients (74.4%) had a PaO2/FiO2 ratio of ≤ 240 and the overall mean (SD) ratio was 208.1 (60.62), with a range of 115.0 to 423.0. The overall mean (SD) change from Baseline was 22.5 (73.17) at EoT and 55.2 (121.1) at ToC.
    End point type
    Other pre-specified
    End point timeframe
    PaO2/FiO2 ratio and the change from Baseline by treatment group and over time on Days 3, 5, 7, 10, EoT, ToC.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10 [58]
    11 [59]
    10 [60]
    8 [61]
    Units: change from Baseline
    arithmetic mean (standard deviation)
        Baseline
    187.40 ( 45.206 )
    224.45 ( 53.097 )
    187.30 ( 31.380 )
    237.70 ( 96.833 )
        Day 3
    29.45 ( 64.515 )
    -15.45 ( 84.131 )
    4.87 ( 51.212 )
    -24.33 ( 57.015 )
        Day 5
    18.70 ( 54.928 )
    -7.80 ( 48.641 )
    -0.70 ( 27.272 )
    11.33 ( 110.937 )
        Day 7
    43.60 ( 60.645 )
    18.13 ( 64.146 )
    2.44 ( 53.247 )
    5.80 ( 105.493 )
        Day 10
    55.25 ( 79.874 )
    19.00 ( 78.042 )
    1.89 ( 70.988 )
    63.33 ( 173.463 )
        EoT
    53.10 ( 71.482 )
    28.27 ( 69.078 )
    16.00 ( 75.584 )
    -15.38 ( 72.419 )
        ToC
    81.89 ( 139.050 )
    54.10 ( 90.235 )
    74.20 ( 156.126 )
    -9.60 ( 118.473 )
    Notes
    [58] - Patients assessed: Baseline to Day 7, EoT (n=10); Day 10 (n=8); ToC (n=9)
    [59] - Patients assessed: Baseline, Day 3, EoT (n=11); Day 5, ToC (n=10); Day 7 (n=8); Day 10 (n=5)
    [60] - Patients assessed: Baseline, Day 3, EoT (n=10); Days 5, 7, 10 (n=9); ToC (n=5)
    [61] - Patients assessed: Baseline, EoT (n=8); Days 3, 5 (n=6); Day 7, ToC (n=5); Day 10 (n=3)
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in mCPIS

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    End point title
    		 Change from Baseline in mCPIS
    End point description
    Changes from Baseline in mCPIS are presented for the micro-ITT population. The mean (SD) mCPIS at Baseline was similar across all treatment groups. The overall mean (SD) change from Baseline at ToC was -5.5 (2.57).
    End point type
    Other pre-specified
    End point timeframe
    Overall scores and the change from Baseline in modified Clinical Pulmonary Infection Score (mCPIS) on Days 3, 5, 7, 10, EoT, and ToC.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10 [62]
    11 [63]
    10 [64]
    8 [65]
    Units: Change from Baseline
    arithmetic mean (standard deviation)
        Baseline
    8.7 ( 2.31 )
    9.0 ( 2.61 )
    9.5 ( 1.51 )
    8.3 ( 1.39 )
        Day 3
    -2.3 ( 1.95 )
    -3.7 ( 3.00 )
    -3.0 ( 2.54 )
    -1.7 ( 1.86 )
        Day 5
    -2.9 ( 1.60 )
    -5.1 ( 2.51 )
    -3.7 ( 2.35 )
    -2.3 ( 1.21 )
        Day 7
    -3.3 ( 2.06 )
    -5.0 ( 2.93 )
    -3.9 ( 2.93 )
    -3.2 ( 1.64 )
        Day 10
    -3.8 ( 2.43 )
    -4.8 ( 2.59 )
    -3.9 ( 2.71 )
    -4.0 ( 3.61 )
        EoT
    -5.3 ( 2.06 )
    -4.9 ( 3.39 )
    -4.9 ( 2.77 )
    -3.6 ( 2.67 )
        ToC
    -5.3 ( 2.60 )
    -5.4 ( 2.76 )
    -6.0 ( 3.61 )
    -5.6 ( 1.52 )
    Notes
    [62] - Patients assessed: Baseline to Day 7 (n=10); Day 10 (n=8); EoT (n=10); ToC (n=9)
    [63] - Patients assessed: Baseline, Day 3, EoT (n=11); Day 5, ToC (n=10); Day 7 (n=8); Day 10 (n=5)
    [64] - Patients assessed: Baseline, Day 3, EoT (n=10); Days 5, 7, 10 (n=9); ToC (n=5)
    [65] - Patients assessed: Baseline, EoT (n=8); Days 3, 5 (n=6); Day 7, ToC (n=5); Day 10 (n=3)
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in SOFA Scores

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    End point title
    		 Change from Baseline in SOFA Scores
    End point description
    Change from Baseline in SOFA scores are presented for the micro-ITT population. The mean (SD) SOFA score at Baseline was similar across all treatment groups. The overall mean (SD) change from Baseline at ToC was -0.9 (2.53).
    End point type
    Other pre-specified
    End point timeframe
    Overall scores and the change from Baseline in Sequential Organ Failure Assessment (SOFA) scores on Days 3, 5, 7, 10, EoT, and ToC.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10 [66]
    11 [67]
    10 [68]
    8 [69]
    Units: Change from Baseline
    arithmetic mean (standard deviation)
        Baseline
    5.8 ( 1.87 )
    6.1 ( 1.04 )
    6.8 ( 1.87 )
    6.8 ( 3.37 )
        Day 3
    0.7 ( 2.54 )
    0.6 ( 1.57 )
    -0.3 ( 1.34 )
    0.3 ( 1.63 )
        Day 5
    0.3 ( 2.95 )
    -0.2 ( 1.48 )
    -1.0 ( 1.87 )
    1.7 ( 2.94 )
        Day 7
    0.2 ( 3.29 )
    -0.1 ( 1.96 )
    -1.7 ( 3.04 )
    3.0 ( 3.67 )
        Day 10
    -0.1 ( 2.23 )
    0.6 ( 1.34 )
    -1.2 ( 2.17 )
    1.3 ( 3.51 )
        EoT
    0.2 ( 1.62 )
    -0.8 ( 2.75 )
    -1.3 ( 2.16 )
    2.4 ( 4.14 )
        ToC
    -0.1 ( 2.62 )
    -2.0 ( 2.62 )
    -1.6 ( 1.52 )
    0.8 ( 2.17 )
    Notes
    [66] - Patients assessed: Baseline to Day 7 (n=10); Day 10 (n=8); EoT (n=10); ToC (n=9)
    [67] - Patients assessed: Baseline, Day 3, EoT (n=11); Day 5, ToC (n=10); Day 7 (n=8); Day 10 (n=5)
    [68] - Patients assessed: Baseline, Day 3, EoT (n=10); Days 5, 7, 10 (n=9); ToC (n=5)
    [69] - Patients assessed: Baseline, EoT (n=8); Days 3, 5 (n=6); Day 7, ToC (n=5); Day 10 (n=3)
    No statistical analyses for this end point

    Other pre-specified: Days Spent in ICU

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    End point title
    		 Days Spent in ICU
    End point description
    The number of days in the ICU are presented for the micro-ITT population. The overall mean (SD) number of days in ICU over a 28-day period was 25.5 (3.97) days and up to hospital discharge was 25.7 (4.14) days. In a sensitivity analysis, the overall mean (SD) number of days in ICU over a 28-day period was 25.5 (3.97) days.
    End point type
    Other pre-specified
    End point timeframe
    The number of calendar days in the Intensive Care Unit (ICU) from randomization up to and including Day 28.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10
    11
    10
    8
    Units: Days
    arithmetic mean (standard deviation)
        Days in ICU over 28-day Period
    26.5 ( 2.59 )
    24.6 ( 4.01 )
    24.2 ( 5.69 )
    26.9 ( 2.23 )
        Days in ICU up to Hospital Discharge
    26.7 ( 2.75 )
    25.0 ( 4.43 )
    24.2 ( 5.69 )
    27.1 ( 2.42 )
        Days in ICU over 28-day Period (sensitivity)
    26.5 ( 2.59 )
    24.6 ( 4.01 )
    24.2 ( 5.69 )
    26.9 ( 2.23 )
    No statistical analyses for this end point

    Other pre-specified: Hospital Stay

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    End point title
    		 Hospital Stay
    End point description
    The number of hospital days are presented for the micro-ITT population. The overall mean (SD) number of hospital days over a 28-day period was 26.9 (2.33) days and up to hospital discharge was 27.2 (2.51) days.
    End point type
    Other pre-specified
    End point timeframe
    The number of calendar days in the hospital from randomization up to and including Day 28.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10
    11
    10
    8
    Units: Days
    arithmetic mean (standard deviation)
        Hospital days over a 28-day Period
    27.4 ( 1.26 )
    26.0 ( 2.72 )
    26.6 ( 3.27 )
    28.0 ( 0.00 )
        Hospital days up to Hospital Discharge
    27.6 ( 1.43 )
    26.4 ( 3.14 )
    26.7 ( 3.33 )
    28.33 ( 0.46 )
    No statistical analyses for this end point

    Other pre-specified: Number of VFDs

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    End point title
    		 Number of VFDs
    End point description
    The number of VFDs are presented for the micro-ITT population. The overall mean (SD) number of VFDs over a 28-day period was 5.6 (8.67) days. In a sensitivity analysis, the overall mean (SD) number of VFDs over a 28-day period was 6.6 (8.79) days.
    End point type
    Other pre-specified
    End point timeframe
    The number of ventilator-free days (VFDs) from randomization over a 28-day period.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10
    11
    10
    8
    Units: Days
    arithmetic mean (standard deviation)
        VFDs over a 28-day Period
    8.2 ( 9.45 )
    6.8 ( 9.73 )
    3.9 ( 7.46 )
    2.8 ( 7.78 )
        VFDs over a 28-day Period (sensitivity)
    8.2 ( 9.45 )
    8.8 ( 9.87 )
    5.2 ( 7.83 )
    3.3 ( 7.70 )
    No statistical analyses for this end point

    Other pre-specified: Clinical Response at ToC - Change in Fever

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    End point title
    		 Clinical Response at ToC - Change in Fever
    End point description
    Assessment of clinical response (improved, worsened, stable, or unchanged) included the evaluation of signs and symptoms of pneumonia. Clinical response data are presented for the micro-ITT population. In general, the majority of clinical response parameters improved or remained unchanged from Baseline to ToC, except for variations in oxygenation (PaO2/FiO2 ratio) across several timepoints. Respiratory secretions and ventilator settings showed an increase in the percentage of patients with worsened values at ToC, compared to Baseline.
    End point type
    Other pre-specified
    End point timeframe
    Clinical response was assessed on Days 3, 5, 7, 10, EoT, and ToC.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10
    11
    10
    8
    Units: subjects
        Improved
    6
    6
    5
    0
        Worsened
    1
    1
    5
    4
        Stable
    2
    2
    0
    3
        Unchanged
    1
    2
    0
    1
        Not assessed
    0
    0
    0
    0
    No statistical analyses for this end point

    Other pre-specified: Clinical Response at ToC - Presence or absence of respiratory secretions

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    End point title
    		 Clinical Response at ToC - Presence or absence of respiratory secretions
    End point description
    Clinical response data are presented for the micro-ITT population.
    End point type
    Other pre-specified
    End point timeframe
    Clinical response was assessed on Days 3, 5, 7, 10, EoT, and ToC.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10
    11
    10
    8
    Units: subjects
        Improved
    7
    4
    4
    5
        Worsened
    1
    1
    5
    3
        Stable
    0
    1
    1
    0
        Unchanged
    2
    5
    0
    0
        Not assessed
    0
    0
    0
    0
    No statistical analyses for this end point

    Other pre-specified: Clinical Response at ToC - Changes in purulence of respiratory secretions

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    End point title
    		 Clinical Response at ToC - Changes in purulence of respiratory secretions
    End point description
    Clinical response data are presented for the micro-ITT population.
    End point type
    Other pre-specified
    End point timeframe
    Clinical response was assessed on Days 3, 5, 7, 10, EoT, and ToC.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10
    11
    10
    8
    Units: subjects
        Improved
    4
    3
    1
    5
        Worsened
    1
    1
    5
    3
        Stable
    0
    0
    1
    0
        Unchanged
    5
    7
    3
    0
        Not assessed
    0
    0
    0
    0
    No statistical analyses for this end point

    Other pre-specified: Clinical Response at ToC - Changes in oxygenation parameters (PaO2/FiO2)

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    End point title
    		 Clinical Response at ToC - Changes in oxygenation parameters (PaO2/FiO2)
    End point description
    Clinical response data are presented for the micro-ITT population.
    End point type
    Other pre-specified
    End point timeframe
    Clinical response was assessed on Days 3, 5, 7, 10, EoT, and ToC.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10
    11
    10
    8
    Units: subjects
        Improved
    5
    6
    2
    3
        Worsened
    4
    3
    7
    5
        Stable
    1
    0
    0
    0
        Unchanged
    0
    2
    1
    0
        Not assessed
    0
    0
    0
    0
    No statistical analyses for this end point

    Other pre-specified: Clinical Response at ToC - Changes in ventilator settings

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    End point title
    		 Clinical Response at ToC - Changes in ventilator settings
    End point description
    Clinical response data are presented for the micro-ITT population.
    End point type
    Other pre-specified
    End point timeframe
    Clinical response was assessed on Days 3, 5, 7, 10, EoT, and ToC.
    End point values
    		 BV100 200 mg + Polymyxin B (Part A) BV100 300 mg + Polymyxin B (Part A) BAT (Part A) BV100 300 mg + BAT (Part B)
    Number of subjects analysed
    10
    11
    10
    8
    Units: subjects
        Improved
    5
    6
    3
    5
        Worsened
    1
    1
    5
    3
        Stable
    0
    0
    1
    0
        Unchanged
    4
    4
    1
    0
        Not assessed
    0
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All AEs and SAEs were to be collected at every visit (from the signing of the ICF until End of Study). All SAEs and AESIs were to be followed until resolution, stabilization, the event was otherwise explained, or the patient was lost to follow-up.
    Adverse event reporting additional description
    AEs were analyzed in the Safety Population. TEAEs occurred in 34 patients (87.2%) overall, with a total of 108 events. Values provided are for TEAEs, defined as those that first occurred or worsened following the start of trial treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Polymyxin B + BV100 (200) - Part A
    Reporting group description
    		 -

    Reporting group title
    Polymyxin B + BV100 (300) - Part A
    Reporting group description
    		 -

    Reporting group title
    BAT - Part A
    Reporting group description
    		 -

    Reporting group title
    BAT + BV100 (300) - Part B
    Reporting group description
    		 All data reported are treatment-emergent events.

    Serious adverse events
    		 Polymyxin B + BV100 (200) - Part A Polymyxin B + BV100 (300) - Part A BAT - Part A BAT + BV100 (300) - Part B
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 10 (30.00%)
    5 / 11 (45.45%)
    6 / 10 (60.00%)
    3 / 8 (37.50%)
         number of deaths (all causes)
    1
    5
    6
    3
         number of deaths resulting from adverse events
    1
    5
    6
    3
    Injury, poisoning and procedural complications
    Intestinal anastomosis complication
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Shock
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 11 (9.09%)
    2 / 10 (20.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    2 / 10 (20.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    General disorders and administration site conditions
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Liver injury
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Septic shock
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Polymyxin B + BV100 (200) - Part A Polymyxin B + BV100 (300) - Part A BAT - Part A BAT + BV100 (300) - Part B
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 10 (90.00%)
    9 / 11 (81.82%)
    6 / 10 (60.00%)
    7 / 8 (87.50%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Atelectasis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Pleural effusion
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 8 (25.00%)
         occurrences all number
    2
    0
    0
    2
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    1
    0
    0
    1
    Bradycardia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Rhythm idioventricular
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nervous system disorders
    Intraventricular haemorrhage
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 10 (20.00%)
    3 / 11 (27.27%)
    0 / 10 (0.00%)
    2 / 8 (25.00%)
         occurrences all number
    2
    3
    0
    2
    Thrombocytopenia
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 11 (9.09%)
    2 / 10 (20.00%)
    1 / 8 (12.50%)
         occurrences all number
    1
    1
    2
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Diarrhoea
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    1
    0
    1
    Gastric haemorrhage
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    3 / 10 (30.00%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    0 / 8 (0.00%)
         occurrences all number
    3
    1
    1
    0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Skin and subcutaneous tissue disorders
    Skin ulcer
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    1
    0
    0
    1
    Haematuria
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Renal impairment
         subjects affected / exposed
    5 / 10 (50.00%)
    2 / 11 (18.18%)
    2 / 10 (20.00%)
    1 / 8 (12.50%)
         occurrences all number
    5
    2
    2
    1
    Infections and infestations
    Abdominal infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Clostridium difficile infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Haematological infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Klebsiella infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Pseudomonas infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Septic shock
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Systemic candida
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypernatraemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 11 (0.00%)
    2 / 10 (20.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Hypocalcaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 11 (9.09%)
    3 / 10 (30.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    1
    3
    0
    Hypomagnesaemia
         subjects affected / exposed
    2 / 10 (20.00%)
    5 / 11 (45.45%)
    2 / 10 (20.00%)
    2 / 8 (25.00%)
         occurrences all number
    2
    5
    2
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 May 2024
    All patients in the trial were randomized/enrolled under Protocol Version 1 (03 October 2022). Protocol Version 2/Amendment 1 (28 May 2024) was approved after patient enrollment was completed; therefore, no patients were enrolled or treated under Version 2. However, all patient data were included to the analysis under Protocol Version 2. As a result, Protocol Version 1 served as the reference version for the CSR. Errors, omissions, or changes implemented in Protocol Version 2 were noted in the CSR where applicable. The overall rationale for Protocol Version 2 (Amendment 1) was to add the following substantial changes: • Clarify Acinetobacter baumannii vs CRAB • Add ToC Visit to Protocol text, where needed • Add when a patient can be switched from Part A to Part B • Clarify polymyxin B references • Clarify when to collect VIP scoring • Clarify timing between Acinetobacter baumannii diagnosis and SARS CoV-2 • Revise upper age limit to be included in the trial • Clarify patients have to be mechanically ventilated continuously to be included in the trial • Clarify for SOFA and mCPIS that if a local laboratory value is not available on the date of a visit, the most recent local laboratory value should be used • Revise frequency of vital signs to once per day • Clarify inclusion criteria regarding what qualifies as documented infection • Clarify exclusion criteria regarding evidence of infection outside the respiratory tract • Revise exclusion criteria regarding QTcF parameter from electrocardiogram

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    This phase 2 study was primarily designed to assess PK and was not powered to draw definitive conclusions on efficacy. The study was conducted in a rare, critically ill population with limited sample size. The data should be interpreted with caution.
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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