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    Clinical Trial Results:
    An Open-Label Non-Randomized, Multi-Center Phase-2 Study of Convection-Enhanced Delivery (CED) of MDNA55 in Adults with Recurrent or Progressive Glioblastoma

    Summary
    EudraCT number
    		 2016-003841-27
    Trial protocol
    		 PL  
    Global end of trial date
    31 Oct 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Dec 2022
    First version publication date
    15 Dec 2022
    Other versions
    Summary report(s)
    		 MDNA55-05 - Synopsis

    Trial information

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    Trial identification
    Sponsor protocol code
    MDNA-55-05
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02858895
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 BB IND: 007004
    Sponsors
    Sponsor organisation name
    Medicenna Therapeutics Inc
    Sponsor organisation address
    2 Bloor Street West, Suite 700, Toronto, ON , Canada, M4W 3E2
    Public contact
    Rosemina Merchant Chief Development Officer , Medicenna Therapeutics Inc., 001 +1 604 340 3081, nmerchant@medicenna.com
    Scientific contact
    Rosemina Merchant Chief Development Officer , Medicenna Therapeutics Inc., 001 +1 604 340 3081, nmerchant@medicenna.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
    05 Mar 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 Sep 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Oct 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study was designed to test the hypothesis that median overall survival (mOS) is improved to a clinically significant degree with MDNA55 administered via CED, as compared to current available treatments for rGBM. The design was based on a null hypothesis that mOS was 8 months (based on a clinically weighted average of published studies of FDA-approved therapies) versus an alternative hypothesis of 11.5 months following MDNA55 treatment.
    Protection of trial subjects
    Conduct of the Clinical Investigation The Investigator will ensure that this study is conducted in full conformance with the principles of the "Declaration of Helsinki” and its amendments, or with the laws and regulations of the locality in which the research is conducted, whichever affords the greater protection to the individual.
    Background therapy
    		 All patients enrolled in the study would have received first line treatment for GBM including surgery and radiotherapy with or without chemotherapy (according to local practice; Stupp protocol, Stupp et al., 2005)
    Evidence for comparator
    		 Not applicable; single arm study
    Actual start date of recruitment
    23 Mar 2017
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy
    Long term follow-up duration
    		 21 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 5
    Country: Number of subjects enrolled
    United States: 42
    Worldwide total number of subjects
    47
    EEA total number of subjects
    5
    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)
    36
    From 65 to 84 years
    11
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Study Initiation Date: First Subject First Visit: 23 Mar 2017 Study Completion Date: Last Subject Last Visit: 12 Sept 2019

    Pre-assignment
    Screening details
    		 Male/ female ≥ 18 yrs; primary (de novo) GB (recurred/progressed per RANO criteria), life expectancy > 12 weeks, KPS ≥ 70; tumor diameter ≥ 1cm x ≥ 1cm (minimum) to 4cm in any direction and no features which make the tumor a poor target for CED (e.g. significant liquefaction or geometric features not conducive to CED).

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    Not applicable

    Arms
    Arm title
    		 MDNA55
    Arm description
    		 Single infusion of MDNA55 via convection enhanced delivery (CED)
    Arm type
    		 Experimental

    Investigational medicinal product name
    cpIL-4PE
    Investigational medicinal product code
    MDNA55
    Other name
    NBI-3001, PRX321
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intratumoral use
    Dosage and administration details
    Single treatment (CED infusion) at doses of either 1.5, 3, 6, or 9 μg/mL and infusion volumes of up to 66 mL (according to tumor size) with a total dose ranging from 18 to 240 μg (within the established MTD of 240 μg)

    Number of subjects in period 1
    		MDNA55
    Started
    47
    Completed
    8
    Not completed
    39
         Consent withdrawn by subject
    3
         Disease progression
    31
         Adverse event, non-fatal
    1
         Death
    2
         hospice
    1
         did not receive drug due to catheters misplaced
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall Trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall Trial Total
    Number of subjects
    		 47 47
    Age categorical
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 36 36
        From 65-84 years
    		 11 11
        85 years and over
    		 0 0
    Age continuous
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: years
        median (full range (min-max))
    		 56 (34 to 78) -
    Gender categorical
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        Female
    		 17 17
        Male
    		 30 30
    Karnofsky Performance Score
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        70
    		 3 3
        80
    		 20 20
        90
    		 19 19
        100
    		 5 5
    MGMT Status
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        Methylated
    		 18 18
        Unmethylated
    		 24 24
        Not Available
    		 5 5
    Steroid Use
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        Yes
    		 19 19
        No
    		 13 13
        Not applicable
    		 14 14
        Missing
    		 1 1
    GBM Grade
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        WHO Grade 4
    		 47 47
    Number of prior relapses
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        1 relapse
    		 37 37
        2 relapses
    		 10 10
    Race
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        American Indian or Alaska Native
    		 0 0
        Asian
    		 2 2
        Black or African American
    		 1 1
        Native Hawaiian or Other Pacific Islander
    		 0 0
        White
    		 41 41
        Other
    		 3 3
    Height
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: cm
        median (full range (min-max))
    		 173 (152 to 190.5) -
    Weight
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: kg
        arithmetic mean (standard deviation)
    		 78.67 ( 16.911 ) -
    Initial Diagnosis to 1st Relapse
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: months
        arithmetic mean (standard deviation)
    		 12.98 ( 7.673 ) -
    Initial Diagnosis to start of MDNA55 treatment
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: months
        arithmetic mean (standard deviation)
    		 15.594 ( 9.1340 ) -
    Max tumor diameter at initial diagnosis
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: cm
        arithmetic mean (standard deviation)
    		 3.331 ( 1.4310 ) -
    Max tumor diameter at baseline
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: cm
        arithmetic mean (standard deviation)
    		 3.160 ( 1.1736 ) -
    Tumor volume at baseline
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: cm3
        arithmetic mean (standard deviation)
    		 10.543 ( 11.0621 ) -
    Lymphocyte count
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: 10^9 cells/L
        arithmetic mean (standard deviation)
    		 0.991 ( 0.3839 ) -
    Subject analysis sets

    Subject analysis set title
    Intent to Treat / Safety Population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Intent-to-Treat and Safety: ITT and Safety populations were identical and consisted of all subjects who signed an informed consent form and received any amount of study drug.

    Subject analysis set title
    Per protocol population
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Per-Protocol Population: PP population consisted of all subjects in the mITT Population who had no major protocol violation during the study. Efficacy analyses were conducted on this population in support of the primary efficacy results.

    Subject analysis set title
    Modified Intent to Treat Population
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    mITT population was used for secondary response analyses and consisted of all subjects who received any amount of study drug, had adequate imaging (at least 1 post-treatment scan), and had sufficient clinical data for ORR analysis.

    Subject analysis sets values
    		 Intent to Treat / Safety Population Per protocol population Modified Intent to Treat Population
    Number of subjects
    47
    44
    43
    Age categorical
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    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)
    36
        From 65-84 years
    11
        85 years and over
    0
    Age continuous
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: years
        median (full range (min-max))
    56 (34 to 78)
    55.5 (34 to 77)
    Gender categorical
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        Female
    17
    17
        Male
    30
    27
    Karnofsky Performance Score
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        70
    3
    3
        80
    20
    19
        90
    19
    19
        100
    5
    3
    MGMT Status
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        Methylated
    18
    17
        Unmethylated
    24
    23
        Not Available
    5
    4
    Steroid Use
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        Yes
    19
    19
        No
    13
    13
        Not applicable
    14
    11
        Missing
    1
    1
    GBM Grade
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        WHO Grade 4
    47
    44
    Number of prior relapses
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        1 relapse
    37
    35
        2 relapses
    10
    9
    Race
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: Subjects
        American Indian or Alaska Native
    0
    0
        Asian
    2
    2
        Black or African American
    1
    1
        Native Hawaiian or Other Pacific Islander
    0
    0
        White
    41
    38
        Other
    3
    3
    Height
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: cm
        median (full range (min-max))
    173 (152 to 190.5)
    172.36 (152 to 190.5)
    Weight
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: kg
        arithmetic mean (standard deviation)
    78.67 ( 16.911 )
    78.46 ( 17.398 )
    ( )
    Initial Diagnosis to 1st Relapse
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: months
        arithmetic mean (standard deviation)
    12.98 ( 7.673 )
    13.14 ( 7.486 )
    ( )
    Initial Diagnosis to start of MDNA55 treatment
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: months
        arithmetic mean (standard deviation)
    15.594 ( 9.1340 )
    15.711 ( 9.1496 )
    ( )
    Max tumor diameter at initial diagnosis
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: cm
        arithmetic mean (standard deviation)
    3.331 ( 1.4310 )
    3.213 ( 1.3987 )
    ( )
    Max tumor diameter at baseline
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: cm
        arithmetic mean (standard deviation)
    3.160 ( 1.1736 )
    3.056 ( 1.0818 )
    ( )
    Tumor volume at baseline
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: cm3
        arithmetic mean (standard deviation)
    10.543 ( 11.0621 )
    10.005 ( 10.9851 )
    ( )
    Lymphocyte count
    Baseline and demographic characteristics will be summarized and presented descriptively.
    Units: 10^9 cells/L
        arithmetic mean (standard deviation)
    0.991 ( 0.3839 )
    0.986 ( 0.3949 )
    ( )

    End points

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    End points reporting groups
    Reporting group title
    MDNA55
    Reporting group description
    		 Single infusion of MDNA55 via convection enhanced delivery (CED)

    Subject analysis set title
    Intent to Treat / Safety Population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Intent-to-Treat and Safety: ITT and Safety populations were identical and consisted of all subjects who signed an informed consent form and received any amount of study drug.

    Subject analysis set title
    Per protocol population
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Per-Protocol Population: PP population consisted of all subjects in the mITT Population who had no major protocol violation during the study. Efficacy analyses were conducted on this population in support of the primary efficacy results.

    Subject analysis set title
    Modified Intent to Treat Population
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    mITT population was used for secondary response analyses and consisted of all subjects who received any amount of study drug, had adequate imaging (at least 1 post-treatment scan), and had sufficient clinical data for ORR analysis.

    Primary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS) [1]
    End point description
    Primary endpoint analysis was based on the ITT population. The null hypothesis was mOS of 8.0 months, based on a clinically-weighted average of published studies of FDA-approved therapies versus the alternative hypothesis of 11.5 months.
    End point type
    Primary
    End point timeframe
    From start of treatment until date of death from any cause. Subjects who were not known to have died at the time of the analysis were to be censored at the date of last contact.
    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: Descriptive statistics (number of subjects [n], mean, standard deviation [SD], minimum, maximum, and median) used to summarize continuous variables. Categorical variables were summarized using frequencies and percentage of subjects within each category. Summaries were provided for overall treatment. Baseline value defined as last non-missing assessment prior to catheter placement. Primary efficacy analysis was to be performed at 0.05 level of significance. No adjustments made for multiplicity.
    End point values
    		 Intent to Treat / Safety Population Per protocol population
    Number of subjects analysed
    47
    44
    Units: months
        median (confidence interval 80%)
    10.2 (8.39 to 12.75)
    11.64 (8.62 to 15.02)
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR)

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    End point title
    		 Objective Response Rate (ORR)
    End point description
    ORR, determined by independent central review (per RANO-based criteria) Complete Response - Disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. Partial Response - ≥50% decrease in sum of products of perpendicular diameters or ≥65% decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks Progressive Disease - At least two sequential scans separated by at ≥4 weeks both exhibiting ≥25% increase in sum of products of perpendicular diameters or ≥40% increase in total volume of enhancing lesions. Stable Disease - Does not qualify for CR, PR, or PD as defined above
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Modified Intent to Treat Population
    Number of subjects analysed
    41 [2]
    Units: participants
        number (not applicable)
    1
    Notes
    [2] - Two subjects were not evaluable and excluded from analysis
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS)

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    End point title
    		 Progression Free Survival (PFS)
    End point description
    PFS, time from treatment until disease progression (per RANO-based criteria) or death Progressive Disease per RANO - At least two sequential scans separated by at ≥4 weeks both exhibiting ≥25% increase in sum of products of perpendicular diameters or ≥40% increase in total volume of enhancing lesions
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Modified Intent to Treat Population
    Number of subjects analysed
    Units: months
        median (confidence interval 80%)
    3.61 (2.79 to 5.08)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs were collected from catheter placement through 12 months post treatment or early withdrawal and followed until resolution, stabilization, data cut-off, or death. For subjects that withdraw from the study, SAEs that occur < 30 days collected.
    Adverse event reporting additional description
    All patients were included in the in the ITT / Safety Population (N=47) for "MDNA55 (Overall)"; there is one patient that underwent catheter placement but did not receive the study drug; the infusion did not proceed due to catheter misplacement. Therefore, this participant is not included in the individual MDNA55 infusion arms (N=46)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22
    Reporting groups
    Reporting group title
    MDNA55 (Overall)
    Reporting group description
    		 Intent-to-Treat/ Safety: ITT/ Safety populations identical and consist of all subjects who signed an informed consent form and received any amount of study drug.

    Reporting group title
    MDNA55 (1.5 mcg/mL)
    Reporting group description
    		 Intent-to-Treat/ Safety: ITT/ Safety populations identical and consist of all subjects who signed an informed consent form and received any amount of study drug.

    Reporting group title
    MDNA55 (3.0 mcg/mL)
    Reporting group description
    		 Intent-to-Treat/ Safety: ITT/ Safety populations identical and consist of all subjects who signed an informed consent form and received any amount of study drug.

    Reporting group title
    MDNA55 (6.0 mcg/mL)
    Reporting group description
    		 -

    Reporting group title
    MDNA55 (9.0 mcg/mL)
    Reporting group description
    		 Intent-to-Treat/ Safety: ITT/ Safety populations identical and consist of all subjects who signed an informed consent form and received any amount of study drug.

    Serious adverse events
    		 MDNA55 (Overall) MDNA55 (1.5 mcg/mL) MDNA55 (3.0 mcg/mL) MDNA55 (6.0 mcg/mL) MDNA55 (9.0 mcg/mL)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    24 / 47 (51.06%)
    6 / 18 (33.33%)
    2 / 9 (22.22%)
    3 / 6 (50.00%)
    9 / 13 (69.23%)
         number of deaths (all causes)
    36
    16
    8
    3
    8
         number of deaths resulting from adverse events
    8
    2
    2
    2
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Peritumoral Oedema
         subjects affected / exposed
    0 / 47 (0.00%)
    1 / 18 (5.56%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 47 (2.13%)
    1 / 18 (5.56%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    3 / 47 (6.38%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
    0 / 0
    1 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral Haemorrhage
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Cerebrovascular Accident
         subjects affected / exposed
    1 / 47 (2.13%)
    1 / 18 (5.56%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemiplegia
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 18 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemorrhage Intracranial
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    2 / 47 (4.26%)
    0 / 18 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolic Encephalopathy
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurological Decompensation
         subjects affected / exposed
    2 / 47 (4.26%)
    1 / 18 (5.56%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Neurological Symptom
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 18 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    8 / 47 (17.02%)
    4 / 18 (22.22%)
    1 / 9 (11.11%)
    2 / 6 (33.33%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    7 / 9
    3 / 5
    1 / 1
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Status Epilepticus
         subjects affected / exposed
    2 / 47 (4.26%)
    0 / 18 (0.00%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Complication of device insertion
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    3 / 47 (6.38%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    Gastrointestinal disorders
    Dysphagia
         subjects affected / exposed
    1 / 47 (2.13%)
    1 / 18 (5.56%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary Embolism
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 47 (2.13%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 47 (4.26%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 47 (4.26%)
    2 / 18 (11.11%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 MDNA55 (Overall) MDNA55 (1.5 mcg/mL) MDNA55 (3.0 mcg/mL) MDNA55 (6.0 mcg/mL) MDNA55 (9.0 mcg/mL)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    46 / 47 (97.87%)
    18 / 18 (100.00%)
    9 / 9 (100.00%)
    6 / 6 (100.00%)
    13 / 13 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 47 (4.26%)
    0 / 18 (0.00%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    1
    1
    0
    Hypotension
         subjects affected / exposed
    4 / 47 (8.51%)
    3 / 18 (16.67%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    4
    3
    1
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    19 / 47 (40.43%)
    8 / 18 (44.44%)
    3 / 9 (33.33%)
    3 / 6 (50.00%)
    5 / 13 (38.46%)
         occurrences all number
    23
    9
    5
    4
    5
    Gait disturbance
         subjects affected / exposed
    7 / 47 (14.89%)
    0 / 18 (0.00%)
    3 / 9 (33.33%)
    1 / 6 (16.67%)
    3 / 13 (23.08%)
         occurrences all number
    10
    0
    3
    4
    3
    Oedema peripheral
         subjects affected / exposed
    3 / 47 (6.38%)
    2 / 18 (11.11%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
         occurrences all number
    3
    2
    0
    1
    0
    Pain
         subjects affected / exposed
    3 / 47 (6.38%)
    1 / 18 (5.56%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
         occurrences all number
    3
    1
    1
    1
    0
    Peripheral swelling
         subjects affected / exposed
    2 / 47 (4.26%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    3
    0
    0
    0
    3
    Pyrexia
         subjects affected / exposed
    2 / 47 (4.26%)
    1 / 18 (5.56%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    1
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Deep vein thrombosis
         subjects affected / exposed
    2 / 47 (4.26%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    2
    0
    0
    0
    2
    Dysphonia
         subjects affected / exposed
    2 / 47 (4.26%)
    1 / 18 (5.56%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
         occurrences all number
    2
    1
    0
    1
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    4 / 47 (8.51%)
    1 / 18 (5.56%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    4
    1
    1
    0
    2
    Anxiety
         subjects affected / exposed
    5 / 47 (10.64%)
    2 / 18 (11.11%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    5
    2
    1
    0
    2
    Confusion
         subjects affected / exposed
    2 / 47 (4.26%)
    1 / 18 (5.56%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    2
    1
    0
    0
    1
    Confusional state
         subjects affected / exposed
    7 / 47 (14.89%)
    4 / 18 (22.22%)
    2 / 9 (22.22%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
         occurrences all number
    7
    4
    2
    1
    0
    Depression
         subjects affected / exposed
    5 / 47 (10.64%)
    0 / 18 (0.00%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    3 / 13 (23.08%)
         occurrences all number
    5
    0
    2
    0
    3
    Insomnia
         subjects affected / exposed
    12 / 47 (25.53%)
    1 / 18 (5.56%)
    4 / 9 (44.44%)
    4 / 6 (66.67%)
    3 / 13 (23.08%)
         occurrences all number
    13
    1
    4
    5
    3
    Irritability
         subjects affected / exposed
    2 / 47 (4.26%)
    0 / 18 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    2
    0
    1
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 47 (8.51%)
    1 / 18 (5.56%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
         occurrences all number
    6
    1
    0
    2
    3
    Blood albumin decreased
         subjects affected / exposed
    2 / 47 (4.26%)
    1 / 18 (5.56%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    5
    4
    1
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    2 / 47 (4.26%)
    1 / 18 (5.56%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    5
    3
    0
    0
    1
    Blood calcium decreased
         subjects affected / exposed
    2 / 47 (4.26%)
    1 / 18 (5.56%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    4
    3
    1
    0
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    4 / 47 (8.51%)
    2 / 18 (11.11%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    4
    2
    0
    0
    2
    Lymphocyte count decreased
         subjects affected / exposed
    5 / 47 (10.64%)
    3 / 18 (16.67%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    13
    10
    2
    0
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    5 / 47 (10.64%)
    1 / 18 (5.56%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
         occurrences all number
    5
    1
    1
    1
    2
    Skin abrasion
         subjects affected / exposed
    2 / 47 (4.26%)
    1 / 18 (5.56%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    2
    1
    0
    0
    1
    Nervous system disorders
    Aphasia
         subjects affected / exposed
    12 / 47 (25.53%)
    4 / 18 (22.22%)
    3 / 9 (33.33%)
    2 / 6 (33.33%)
    3 / 13 (23.08%)
         occurrences all number
    18
    4
    4
    5
    5
    Brain oedema
         subjects affected / exposed
    5 / 47 (10.64%)
    1 / 18 (5.56%)
    3 / 9 (33.33%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    6
    1
    3
    0
    2
    Cognitive disorder
         subjects affected / exposed
    4 / 47 (8.51%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    3 / 6 (50.00%)
    1 / 13 (7.69%)
         occurrences all number
    4
    0
    0
    3
    1
    Dizziness
         subjects affected / exposed
    4 / 47 (8.51%)
    2 / 18 (11.11%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    5
    2
    3
    0
    0
    Dysarthria
         subjects affected / exposed
    4 / 47 (8.51%)
    2 / 18 (11.11%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
         occurrences all number
    6
    3
    1
    2
    0
    Epilepsy
         subjects affected / exposed
    2 / 47 (4.26%)
    2 / 18 (11.11%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    3
    3
    0
    0
    0
    Extensor plantar response
         subjects affected / exposed
    2 / 47 (4.26%)
    1 / 18 (5.56%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    1
    1
    0
    0
    Facial paralysis
         subjects affected / exposed
    2 / 47 (4.26%)
    0 / 18 (0.00%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
         occurrences all number
    4
    0
    1
    3
    0
    Facial paresis
         subjects affected / exposed
    7 / 47 (14.89%)
    2 / 18 (11.11%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    3 / 13 (23.08%)
         occurrences all number
    7
    2
    2
    0
    3
    Headache
         subjects affected / exposed
    18 / 47 (38.30%)
    10 / 18 (55.56%)
    2 / 9 (22.22%)
    4 / 6 (66.67%)
    2 / 13 (15.38%)
         occurrences all number
    35
    10
    7
    13
    5
    Hemiparesis
         subjects affected / exposed
    12 / 47 (25.53%)
    4 / 18 (22.22%)
    2 / 9 (22.22%)
    1 / 6 (16.67%)
    5 / 13 (38.46%)
         occurrences all number
    17
    4
    2
    4
    7
    Hypoaesthesia
         subjects affected / exposed
    2 / 47 (4.26%)
    0 / 18 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    5
    0
    4
    0
    1
    Memory impairment
         subjects affected / exposed
    5 / 47 (10.64%)
    0 / 18 (0.00%)
    1 / 9 (11.11%)
    2 / 6 (33.33%)
    2 / 13 (15.38%)
         occurrences all number
    6
    0
    1
    3
    2
    Paraesthesia
         subjects affected / exposed
    7 / 47 (14.89%)
    2 / 18 (11.11%)
    2 / 9 (22.22%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
         occurrences all number
    7
    2
    2
    1
    2
    Partial seizures
         subjects affected / exposed
    2 / 47 (4.26%)
    1 / 18 (5.56%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    2
    1
    0
    0
    1
    Pyramidal tract syndrome
         subjects affected / exposed
    8 / 47 (17.02%)
    1 / 18 (5.56%)
    1 / 9 (11.11%)
    3 / 6 (50.00%)
    3 / 13 (23.08%)
         occurrences all number
    17
    2
    1
    9
    5
    Seizure
         subjects affected / exposed
    14 / 47 (29.79%)
    4 / 18 (22.22%)
    2 / 9 (22.22%)
    5 / 6 (83.33%)
    3 / 13 (23.08%)
         occurrences all number
    17
    5
    2
    7
    3
    Simple partial seizure
         subjects affected / exposed
    2 / 47 (4.26%)
    1 / 18 (5.56%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    1
    1
    0
    0
    Tremor
         subjects affected / exposed
    3 / 47 (6.38%)
    1 / 18 (5.56%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    3
    1
    0
    1
    2
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    2 / 47 (4.26%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    2
    0
    0
    0
    2
    Eye disorders
    Vision blurred
         subjects affected / exposed
    6 / 47 (12.77%)
    2 / 18 (11.11%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
         occurrences all number
    6
    2
    1
    1
    2
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    8 / 47 (17.02%)
    3 / 18 (16.67%)
    1 / 9 (11.11%)
    2 / 6 (33.33%)
    2 / 13 (15.38%)
         occurrences all number
    8
    3
    1
    2
    2
    Diarrhoea
         subjects affected / exposed
    4 / 47 (8.51%)
    2 / 18 (11.11%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    5
    2
    1
    0
    2
    Nausea
         subjects affected / exposed
    8 / 47 (17.02%)
    3 / 18 (16.67%)
    2 / 9 (22.22%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
         occurrences all number
    10
    3
    3
    2
    2
    Vomiting
         subjects affected / exposed
    6 / 47 (12.77%)
    2 / 18 (11.11%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    8
    2
    3
    0
    3
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    2 / 47 (4.26%)
    0 / 18 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    2
    0
    0
    1
    1
    Renal and urinary disorders
    Pollakiuria
         subjects affected / exposed
    3 / 47 (6.38%)
    1 / 18 (5.56%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
         occurrences all number
    4
    2
    1
    1
    0
    Urinary incontinence
         subjects affected / exposed
    2 / 47 (4.26%)
    1 / 18 (5.56%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
         occurrences all number
    2
    1
    0
    1
    0
    Endocrine disorders
    Cushingoid
         subjects affected / exposed
    2 / 47 (4.26%)
    1 / 18 (5.56%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    2
    1
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    5 / 47 (10.64%)
    1 / 18 (5.56%)
    1 / 9 (11.11%)
    2 / 6 (33.33%)
    1 / 13 (7.69%)
         occurrences all number
    6
    2
    1
    2
    1
    Muscular weakness
         subjects affected / exposed
    15 / 47 (31.91%)
    8 / 18 (44.44%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    5 / 13 (38.46%)
         occurrences all number
    18
    9
    1
    2
    6
    Pain in extremity
         subjects affected / exposed
    3 / 47 (6.38%)
    1 / 18 (5.56%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    3
    1
    1
    0
    1
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    7 / 47 (14.89%)
    3 / 18 (16.67%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    3 / 13 (23.08%)
         occurrences all number
    7
    3
    0
    1
    3
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    6 / 47 (12.77%)
    2 / 18 (11.11%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    3 / 13 (23.08%)
         occurrences all number
    6
    2
    0
    1
    3
    Dehydration
         subjects affected / exposed
    2 / 47 (4.26%)
    1 / 18 (5.56%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    2
    1
    0
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    3 / 47 (6.38%)
    2 / 18 (11.11%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    5
    2
    3
    0
    0
    Hypokalaemia
         subjects affected / exposed
    7 / 47 (14.89%)
    3 / 18 (16.67%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
         occurrences all number
    7
    3
    1
    1
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Apr 2017
    Amendment 1 (dated 26 Apr 2017, Protocol Version 2.0) The reason for this amendment was to update protocol and inclusion criteria to reflect current treatment practices and disease assessment tools and refining the guidance for study drug administration.
    14 Aug 2017
    Amendment 2 (dated 14 Aug 2017, Protocol Version 3.0) The reason for this amendment was to include key changes to infusion parameters to enhance drug delivery and increase drug concentration; shift to a fixed dose approach with 180 μg administered via four catheters; clarifications and refinements to inclusion criteria and simplify study procedures; and provision to recruit additional subjects for preplanned analysis to retain power under new dosing regimen.
    18 Dec 2017
    Amendment 3 (dated 18 Dec 2017, Protocol Version 4.0) The overall reason for this amendment was to incorporate further changes advised on precautionary basis to infusion parameters (due to neurotoxicity events at a single site) and to clarify the reduction in dose concentration of both MDNA55 and Gd-DTPA.

    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.
    NA

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/33863808
    http://www.ncbi.nlm.nih.gov/pubmed/34345478
    http://www.ncbi.nlm.nih.gov/pubmed/34592195
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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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