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    Clinical Trial Results:
    Phase I/II Trial Investigating an Immunostimulatory Oncolytic Adenovirus for Cancer

    Summary
    EudraCT number
    		 2017-002565-22
    Trial protocol
    		 SE  
    Global end of trial date
    22 Aug 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Sep 2024
    First version publication date
    04 Sep 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    LOKON002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03225989
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Lokon Pharma AB
    Sponsor organisation address
    Bredgrand 14, Uppsala, Sweden, 75320
    Public contact
    Angelica Loskog, Lokon Pharma AB, angelica.loskog@lokonpharma.com
    Scientific contact
    Angelica Loskog, Lokon Pharma AB, angelica.loskog@lokonpharma.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
    22 Aug 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    22 Aug 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Aug 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective is to determine the tolerability of increasing doses of LOAd703 intratumoral injections during standard of care or added conditioning chemotherapy.
    Protection of trial subjects
    The study was conducted in accordance to the protocol, applicable regulatory requirements, GCP and ethical principals of the latest version of the Declaration of Helsinki. The principal investigators were responsible for ensuring the protocol is followed. Safeguards to protect clinical research volunteers include Institutional Review Boards/Independent Ethics Committee, informed consent and cohort review safety meetings.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Apr 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Sweden: 42
    Worldwide total number of subjects
    42
    EEA total number of subjects
    42
    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)
    23
    From 65 to 84 years
    19
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Overall, a total of 47 subjects were screened, 42 subjects were enrolled in the study and 5 subjects were screening failures. One out of 42 enrolled did not received any LOAd703 treatment. The study enrollment was stopped after obtaining sufficient safety data, and subjects were followed until the End of Study was reached as per protocol.

    Pre-assignment
    Screening details
    		 Adult patients (≥18 years of age) with a pathological confirmation of colorectal carcinoma, pancreatic carcinoma, biliary cancer, or epithelial ovarian carcinoma (encompassed epithelial ovarian, fallopian tube or primary peritoneal carcinoma), have advanced disease (metastatic or locally advanced unresectable), were eligible for the study.

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

    Arms
    Arm title
    		 Treatment arm
    Arm description
    		 LOAD703 (Delolimogene mupadenorepvec) at three dose levels: 5x10e10 VP, 1x10e11 VP and 5x10e11 VP as add-on to standard-of care for each indication. Treatments of LOAd703 (up to 8 times) were delivered by intratumoral injection every 2 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LOAd703
    Investigational medicinal product code
    Other name
    delolimogene mupadenorepvec
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intratumoral use
    Dosage and administration details
    Modified adenovirus serotype 5/35 containing a CMV promoter-driven transgene cassette with human transgenes encoding membrane-bound CD40 ligand (TMZ-CD40L) and full-length 4-1BBL. LOAd703 was tested at three dose levels: 5x10e10VP, 1x10e11VP and 5x10e11VP. LOAd703 is delivered frozen in vials containing 650 µl of virus in suspension. The frozen vial is thawed at the clinic on wet ice or in a refrigerator +4°C (±2°C) according to the Sponsor’s instructions. The thawed LOAd703 virus is used directly or is diluted with physiological saline (0.9% NaCl) prior use depending on the patient dose and number of lesions to be injected. The Investigator and the radiologist assess together which lesion(s) are suitable for direct or image guided injection. The prescribed virus dose in suspension is administered by i.t. injections into ≤3 lesions per treatment occasion.

    Number of subjects in period 1
    		Treatment arm
    Started
    42
    Completed
    4
    Not completed
    38
         Clinical progression
    1
         Consent withdrawn by subject
    1
         Physician decision
    1
         Patient decision to stop treatment
    1
         Adverse event, non-fatal
    3
         Death
    5
         Progressive disease
    25
         LOAd703 treatment not started
    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
    		 42 42
    Age categorical
    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)
    		 23 23
        From 65-84 years
    		 19 19
        85 years and over
    		 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 63.0 (33.0 to 77.0) -
    Gender categorical
    Units: Subjects
        Female
    		 23 23
        Male
    		 19 19
    Race
    Units: Subjects
        White
    		 42 42
    Oncological disease at study entry
    Locally advanced cancer is cancer that has spread from where it started to nearby tissue or lymph nodes. Metastatic cancer is spread of cancer from the primary site to other places in the body.
    Units: Subjects
        Locally advanced
    		 8 8
        Metastatic
    		 34 34
    Subject analysis sets

    Subject analysis set title
    LOAD703 dose 5x10e10 VP
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    LOAd703 dose is 5x10e10 VP as add-on to standard-of-care tailored to the indication.

    Subject analysis set title
    LOAD703 dose 1x10e11 VP
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    LOAd703 dose is 1x10e11 VP as add-on to standard-of-care tailored to the indication.

    Subject analysis set title
    LOAd703 dose 5x10e11 VP
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    LOAd703 dose is 5x10e11 VP as add-on to standard-of-care tailored to the indication.

    Subject analysis set title
    Colorectal cancer
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects diagnosed with colorectal cancer

    Subject analysis set title
    Biliary cancer
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects diagnosed with biliary cancer

    Subject analysis set title
    Pancreatic cancer
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects diagnosed with pancreatic cancer

    Subject analysis set title
    Ovarian cancer
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects diagnosed with ovarian cancer

    Subject analysis sets values
    		 LOAD703 dose 5x10e10 VP LOAD703 dose 1x10e11 VP LOAd703 dose 5x10e11 VP Colorectal cancer Biliary cancer Pancreatic cancer Ovarian cancer
    Number of subjects
    3
    12
    27
    5
    3
    29
    5
    Age categorical
    Units: Subjects
        In utero
    0
    0
    0
    0
    0
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
    0
    0
    0
    0
    0
        Newborns (0-27 days)
    0
    0
    0
    0
    0
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
    0
    0
    0
    0
    0
        Children (2-11 years)
    0
    0
    0
    0
    0
    0
    0
        Adolescents (12-17 years)
    0
    0
    0
    0
    0
    0
    0
        Adults (18-64 years)
    2
    5
    16
    3
    1
    16
    3
        From 65-84 years
    1
    7
    11
    2
    2
    13
    2
        85 years and over
    0
    0
    0
    0
    0
    0
    0
    Age continuous
    Units: years
        median (full range (min-max))
    58.0 (42.0 to 67.0)
    67.0 (33.0 to 76.0)
    63.0 (48.0 to 77.0)
    57.0 (42.0 to 73.0)
    72.0 (61.0 to 74.0)
    63.0 (48.0 to 77.0)
    52.0 (33.0 to 75.0)
    Gender categorical
    Units: Subjects
        Female
    0
    6
    17
    2
    3
    13
    5
        Male
    3
    6
    10
    3
    0
    16
    0
    Race
    Units: Subjects
        White
    3
    12
    27
    5
    3
    29
    5
    Oncological disease at study entry
    Locally advanced cancer is cancer that has spread from where it started to nearby tissue or lymph nodes. Metastatic cancer is spread of cancer from the primary site to other places in the body.
    Units: Subjects
        Locally advanced
    0
    4
    4
    0
    0
    8
    0
        Metastatic
    3
    8
    23
    5
    3
    21
    5

    End points

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    End points reporting groups
    Reporting group title
    Treatment arm
    Reporting group description
    		 LOAD703 (Delolimogene mupadenorepvec) at three dose levels: 5x10e10 VP, 1x10e11 VP and 5x10e11 VP as add-on to standard-of care for each indication. Treatments of LOAd703 (up to 8 times) were delivered by intratumoral injection every 2 weeks.

    Subject analysis set title
    LOAD703 dose 5x10e10 VP
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    LOAd703 dose is 5x10e10 VP as add-on to standard-of-care tailored to the indication.

    Subject analysis set title
    LOAD703 dose 1x10e11 VP
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    LOAd703 dose is 1x10e11 VP as add-on to standard-of-care tailored to the indication.

    Subject analysis set title
    LOAd703 dose 5x10e11 VP
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    LOAd703 dose is 5x10e11 VP as add-on to standard-of-care tailored to the indication.

    Subject analysis set title
    Colorectal cancer
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects diagnosed with colorectal cancer

    Subject analysis set title
    Biliary cancer
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects diagnosed with biliary cancer

    Subject analysis set title
    Pancreatic cancer
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects diagnosed with pancreatic cancer

    Subject analysis set title
    Ovarian cancer
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects diagnosed with ovarian cancer

    Primary: Safety determined by the NCI-CTCAE v4.03

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    End point title
    		 Safety determined by the NCI-CTCAE v4.03 [1]
    End point description
    End point type
    Primary
    End point timeframe
    40 weeks
    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: No formal statistical analysis was performed to compare dose or cancer groups. Results are presented with descriptive statistics, are tabulated by groups and reviewed to evaluate the study endpoints.
    End point values
    		 LOAD703 dose 5x10e10 VP LOAD703 dose 1x10e11 VP LOAd703 dose 5x10e11 VP
    Number of subjects analysed
    3 [2]
    12 [3]
    26 [4]
    Units: Number of events
        All Adverse events (AEs)
    61
    139
    411
        All Serious adverse events (SAEs)
    7
    31
    63
        Serious adverse reactions related to LOAd703
    3
    4
    21
        AE leading to LOAd703 discontinuation
    0
    2
    6
        AE leading to withdrawal from the study
    0
    1
    2
        AE leading to death
    0
    0
    1
        AE related to LOAd703
    29
    33
    169
        AE related to LOAd703 grade 1
    15
    29
    111
        AE related to LOAd703 grade 2
    14
    3
    52
        AE related to LOAd703 grade 3
    0
    0
    6
        AE related to LOAd703 grade 4
    0
    1
    0
        AE related to LOAd703 grade 5
    0
    0
    0
        AE unrelated to LOAd703
    32
    106
    242
    Notes
    [2] - Number of subjects based on safety evaluable population (at least one LOAd703 treatment received)
    [3] - Number of subjects based on safety evaluable population (at least one LOAd703 treatment received)
    [4] - Number of subjects based on safety evaluable population (at least one LOAd703 treatment received)
    No statistical analyses for this end point

    Secondary: Best overall tumor response according to RECIST 1.1

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    End point title
    		 Best overall tumor response according to RECIST 1.1
    End point description
    Overall Response Rate is defined as proportion of subjects with the best overall response of complete response (CR) or partial response (PR). Clinical Benefit Rate is defined as proportion of subjects with the best overall response of complete response (CR) or partial response (PR) or stable disease (SD).
    End point type
    Secondary
    End point timeframe
    40 weeks
    End point values
    		 LOAD703 dose 5x10e10 VP LOAD703 dose 1x10e11 VP LOAd703 dose 5x10e11 VP Colorectal cancer Biliary cancer Pancreatic cancer Ovarian cancer
    Number of subjects analysed
    3 [5]
    10 [6]
    22 [7]
    5 [8]
    3 [9]
    24 [10]
    3 [11]
    Units: Number of subjects
        Complete response
    0
    0
    0
    0
    0
    0
    0
        Partial response
    0
    3
    3
    0
    0
    6
    0
        Stable disease
    1
    4
    11
    2
    1
    11
    2
        Progressive disease
    2
    3
    8
    3
    2
    7
    1
        Not evaluable
    0
    0
    0
    0
    0
    0
    0
        Overall response rate (CR or PR)
    0
    3
    3
    0
    0
    6
    0
        Clinical benefit rate (CR, PR or SD)
    1
    7
    14
    2
    1
    17
    2
    Notes
    [5] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [6] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [7] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [8] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [9] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [10] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [11] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    No statistical analyses for this end point

    Secondary: Overall survival

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    End point title
    		 Overall survival
    End point description
    Overall survival is defined as the time from the first dose of LOAd703 treatment until death.
    End point type
    Secondary
    End point timeframe
    up to 72 months
    End point values
    		 Treatment arm LOAD703 dose 5x10e10 VP LOAD703 dose 1x10e11 VP LOAd703 dose 5x10e11 VP Colorectal cancer Biliary cancer Pancreatic cancer Ovarian cancer
    Number of subjects analysed
    35 [12]
    3 [13]
    10 [14]
    22 [15]
    5 [16]
    3 [17]
    24 [18]
    3 [19]
    Units: months
        median (confidence interval 95%)
    7.46 (5.49 to 10.48)
    4.40 (3.02 to 12.85)
    8.44 (2.66 to 40.54)
    7.38 (5.39 to 10.71)
    5.36 (3.02 to 8.44)
    6.64 (5.26 to 7.46)
    7.29 (5.39 to 12.85)
    40.54 (9.69 to 40.54)
    Notes
    [12] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [13] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [14] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [15] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [16] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [17] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [18] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [19] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    No statistical analyses for this end point

    Secondary: Progression free survivial

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    End point title
    		 Progression free survivial
    End point description
    Progression free survival is defined as the time from the first dose of LOAd703 treatment until progression according to RECIST1.1 or death (whichever occurred first).
    End point type
    Secondary
    End point timeframe
    up to 72 months
    End point values
    		 Treatment arm LOAD703 dose 5x10e10 VP LOAD703 dose 1x10e11 VP LOAd703 dose 5x10e11 VP Colorectal cancer Biliary cancer Pancreatic cancer Ovarian cancer
    Number of subjects analysed
    35 [20]
    3 [21]
    10 [22]
    22 [23]
    5 [24]
    3 [25]
    24 [26]
    3 [27]
    Units: months
        median (confidence interval 95%)
    3.75 (2.27 to 5.49)
    2.40 (1.74 to 3.68)
    3.79 (1.81 to 5.49)
    4.32 (1.87 to 5.72)
    2.40 (1.74 to 5.36)
    1.81 (1.58 to 4.76)
    4.62 (2.27 to 5.72)
    3.88 (1.87 to 20.07)
    Notes
    [20] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [21] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [22] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [23] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [24] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [25] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [26] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [27] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    No statistical analyses for this end point

    Secondary: Time to progression

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    End point title
    		 Time to progression
    End point description
    Time to progression (TTP) defined as the time from first dose of LOAd703 treatment until progression according to RECIST v1.1.
    End point type
    Secondary
    End point timeframe
    up to 72 months
    End point values
    		 Treatment arm LOAD703 dose 5x10e10 VP LOAD703 dose 1x10e11 VP LOAd703 dose 5x10e11 VP Colorectal cancer Biliary cancer Pancreatic cancer Ovarian cancer
    Number of subjects analysed
    35 [28]
    3 [29]
    10 [30]
    22 [31]
    5 [32]
    3 [33]
    24 [34]
    3 [35]
    Units: months
        median (confidence interval 95%)
    3.71 (2.10 to 5.49)
    2.40 (1.74 to 3.68)
    3.79 (1.81 to 5.49)
    3.88 (1.87 to 5.72)
    2.40 (1.74 to 3.84)
    1.81 (1.58 to 4.76)
    3.75 (2.27 to 5.72)
    3.88 (1.87 to 20.07)
    Notes
    [28] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [29] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [30] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [31] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [32] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [33] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [34] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    [35] - Number of subjects based on efficacy evaluable population (at least 3 LOAd703 inj+CT evaluation)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    40 weeks
    Adverse event reporting additional description
    The AE reporting period for this study begins upon receiving the first LOAd703 treatment and continues until final visit at week 40. If a patient experiences an AE after signing the informed consent but before the first treatment, the event may be recorded as medical condition.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    LOAd703 dose 5x10e10VP
    Reporting group description
    		 -

    Reporting group title
    LOAd703 dose 1x10e11VP
    Reporting group description
    		 -

    Reporting group title
    LOAd703 dose 5x10e11VP
    Reporting group description
    		 -

    Serious adverse events
    		 LOAd703 dose 5x10e10VP LOAd703 dose 1x10e11VP LOAd703 dose 5x10e11VP
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    12 / 12 (100.00%)
    20 / 26 (76.92%)
         number of deaths (all causes)
    3
    10
    23
         number of deaths resulting from adverse events
    0
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 12 (16.67%)
    11 / 26 (42.31%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 3
    10 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    3 / 26 (11.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    4 / 26 (15.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    6 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device dislocation
    Additional description: NP-catheter dislocation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatine increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Seizure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 12 (16.67%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer perforation
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
    Additional description: Rash generalized
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glomerulonephritis membranoproliferative
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Clostridial infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 12 (16.67%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    4 / 26 (15.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 LOAd703 dose 5x10e10VP LOAd703 dose 1x10e11VP LOAd703 dose 5x10e11VP
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    11 / 12 (91.67%)
    26 / 26 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    3
    Tumour pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2
    Tumour thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 12 (16.67%)
    4 / 26 (15.38%)
         occurrences all number
    4
    2
    4
    Hypotension
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 12 (16.67%)
    3 / 26 (11.54%)
         occurrences all number
    0
    2
    6
    Deep vein thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2
    Embolism
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    3 / 3 (100.00%)
    3 / 12 (25.00%)
    11 / 26 (42.31%)
         occurrences all number
    7
    3
    25
    Fatigue
         subjects affected / exposed
    2 / 3 (66.67%)
    7 / 12 (58.33%)
    16 / 26 (61.54%)
         occurrences all number
    5
    9
    19
    General physical health deterioration
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    1
    0
    2
    Malaise
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    1
    0
    1
    Oedema peripheral
         subjects affected / exposed
    2 / 3 (66.67%)
    5 / 12 (41.67%)
    6 / 26 (23.08%)
         occurrences all number
    2
    7
    7
    Pyrexia
         subjects affected / exposed
    3 / 3 (100.00%)
    8 / 12 (66.67%)
    24 / 26 (92.31%)
         occurrences all number
    9
    10
    66
    Discomfort
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    2
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Injection site oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Localised oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    1
    Face oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Feeling cold
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Generalised oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Influenza like illness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Injection site inflammation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Injection site pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2
    Mucosal inflammation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    3
    Pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Swelling
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 12 (16.67%)
    2 / 26 (7.69%)
         occurrences all number
    2
    2
    2
    Lung infiltration
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 12 (8.33%)
    2 / 26 (7.69%)
         occurrences all number
    1
    1
    2
    Hypoxia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Cough
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    3
    Epistaxis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2
    Pleural effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2
    Pulmonary embolism
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2
    Respiratory failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    4 / 26 (15.38%)
         occurrences all number
    0
    1
    4
    Blood bilirubin increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    2 / 26 (7.69%)
         occurrences all number
    0
    1
    2
    C-reactive protein increased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 12 (16.67%)
    6 / 26 (23.08%)
         occurrences all number
    0
    2
    6
    Cardiac murmur
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Electrocardiogram abnormal
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Heart rate irregular
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    2 / 26 (7.69%)
         occurrences all number
    0
    1
    2
    Neutrophil count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    5 / 26 (19.23%)
         occurrences all number
    0
    1
    5
    Weight decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    3 / 26 (11.54%)
         occurrences all number
    0
    1
    3
    White blood cell count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    5 / 26 (19.23%)
         occurrences all number
    0
    1
    6
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    3 / 26 (11.54%)
         occurrences all number
    0
    0
    3
    Blood albumin decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2
    Blood pressure decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Platelet count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    2
    Transaminases increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Weight increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Injury, poisoning and procedural complications
    Incisional hernia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Muscle strain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Peripancreatic fluid collection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 12 (16.67%)
    0 / 26 (0.00%)
         occurrences all number
    0
    2
    0
    Palpitations
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Atrial fibrillation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Pericardial effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 12 (16.67%)
    6 / 26 (23.08%)
         occurrences all number
    1
    7
    11
    Neuropathy peripheral
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    3 / 26 (11.54%)
         occurrences all number
    0
    1
    3
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Syncope
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Dizziness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Dysgeusia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2
    Paraesthesia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Posterior reversible encephalopathy syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Tremor
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    4 / 12 (33.33%)
    8 / 26 (30.77%)
         occurrences all number
    1
    5
    11
    Leukopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    1
    Neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 12 (25.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    3
    2
    Thrombocytopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    1
    Thrombocytosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Eye disorders
    Periorbital oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    4 / 26 (15.38%)
         occurrences all number
    1
    0
    5
    Nausea
         subjects affected / exposed
    2 / 3 (66.67%)
    5 / 12 (41.67%)
    16 / 26 (61.54%)
         occurrences all number
    2
    6
    18
    Proctalgia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    0
    Stomatitis
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    1
    1
    0
    Vomiting
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 12 (16.67%)
    10 / 26 (38.46%)
         occurrences all number
    7
    2
    17
    Abdominal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 12 (16.67%)
    5 / 26 (19.23%)
         occurrences all number
    0
    2
    6
    Ascites
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 12 (16.67%)
    6 / 26 (23.08%)
         occurrences all number
    0
    2
    6
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    1
    Change of bowel habit
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2
    Colitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Faeces discoloured
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Gastritis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2
    Gingival blister
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Mesenteric vein thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Rash
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    2
    Alopecia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Eczema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Pain of skin
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Urticaria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2
    Renal and urinary disorders
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 12 (25.00%)
    3 / 26 (11.54%)
         occurrences all number
    0
    3
    3
    Glomerulonephritis membranoproliferative
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Urinary retention
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    0
    Back pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    2
    0
    1
    Myalgia
         subjects affected / exposed
    2 / 3 (66.67%)
    1 / 12 (8.33%)
    4 / 26 (15.38%)
         occurrences all number
    3
    1
    4
    Groin pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    3 / 26 (11.54%)
         occurrences all number
    0
    0
    4
    Pain in extremity
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Infections and infestations
    Clostridial infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Erysipelas
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    1
    Infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 12 (16.67%)
    2 / 26 (7.69%)
         occurrences all number
    0
    3
    3
    Oral candidiasis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Oral fungal infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    Cystitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Device related infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Groin infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Infusion related reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 12 (8.33%)
    3 / 26 (11.54%)
         occurrences all number
    1
    1
    3
    Hypokalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    2 / 26 (7.69%)
         occurrences all number
    0
    1
    2
    Hyponatraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Apr 2019
    Substantial changes: Platinum-resistance disease has been added to the definition of the ovarian cancer population (section 2.7.4 and 4.1) Continuation criteria to consider when assessing the patient prior to next LOAD703 injection, has been added, (section 5.1, 5.2 ) Follow-up of patients after injection has been extended: overnight stays, vital signs, (section 5.1, 5.2) Information on immediate reactions to the LOAd703 virus particle cytokine release syndrome and their handling plans, has been added (section 9.4.1 and 9.4.3). The use of corticosteroids during study has been added to as the pre-medication list under certain conditions (section 5.11) Information on DLT assessment and dose adjustments, has been added (section 4.4, 5.1, 5.6 and 5.7) INR/PT and aPTT/PTT are added to the lab list before injections/biopsy (section 7.2.8) Administrative changes.
    15 Nov 2019
    Substantial changes: Exclusion criteria nr 4: “patients on warfarin (or other anti-coagulants) are not eligible” has been changed to not exclude patients on other anti-coagulants than warfarin since the hospital guidelines regarding such patients has been changed. They are now eligible for injections and biopsy and can therefore be enrolled in this trial. Synopsis, section 4.2 and 6.3 are updated accordingly. Karolinska Hospital is included as a new site and the trial is therefore not single center but multi center. Patient samples from patients enrolled at Karolinska Hospital will be temporarily stored in their biobank. Synopsis, 1.4-6, 1.10.2, 3.3, 4, 5.4,1, 5.4.3, 7.1.1, 12.2 and 14.5 are updated accordingly. Administrative changes.
    02 Jan 2020
    Substantial change: Sections 5.5.3 and 5.5.5 are modified to allow storage of an unopened, thawed virus vial up to 24 hours in refrigerator and to change dilution buffer to physiological saline in accordance with the approved IMPD (version 5) and IB (version 6).
    06 Dec 2021
    Substantial changes: Phase II is divided in phase IIa and phase IIb. In phase IIb additional pancreas cancer (PC) and ovarian cancer patients (EOC) are enrolled. Enrolment of biliary cancer and colorectal cancer patients is stopped (synopsis, section 3.3 and 10.2.2) Inclusion of two dose levels (1x1011 VP and 5x1011VP) in Phase IIb (synopsis, section 3.3, 5.2 and 10.2.2) Expansion of total accrual in phase II to achieve up to 53 efficacy evaluable patients (phase IIa: 18, phase IIb: up to 35) (synopsis, section 3.3, and 10.2.2, 10.4). The total number of patients to be enrolled in the study is 80. Extension of study duration to 72 months (synopsis, section 3.4) Update of inclusion criteria for PC patients (no. 3bi): LOAd703 is an add-on to SoC treatment at first and second line. (synopsis, section 2.7.2 and 4.1) Update of inclusion criteria for EOC patients. Inclusion criterion no. 3di was removed and inclusion criteria no.3dii-iv) were updated to include: - patients with platinum-sensitive relapse that previously received at least one line of chemotherapy and not eligible for PARP-inhibitor maintenance; - patients with platinum-resistant relapse, who have not received more than two lines of appropriate standard of care and not eligible for bevacizumab. Maintenance treatment does not count as a line of therapy; - patients that have received appropriate therapy with PARP inhibitors if eligible (synopsis, section 2.7.4 and 4.1). Update regarding chemotherapy schedule for EOC patients in the extended phase IIb (section 5.10.4) Addition of exclusion criteria no. 12 and 13 to exclude patients having received adenovirus based gene therapy and adenovirus-based vaccine prior to LOAd703 treatment (synopsis, section 4.2) Addition of severe (grade 3) cytokine release syndrome (CRS) as condition for dose reduction Update regarding reporting of chemotherapy-induced bone marrow toxicities Administrative changes
    21 Dec 2022
    Non-substantial amendment. Administrative changes only.

    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.
    Exploratory analysis for shedding, anti-adenovirus immunity, PK atezolizumab, immunity to atezolizumab, immune and protein profile was done. Results are summarized per individual subjects or over time without statistical analysis. Data not submitted.
    For support, Contact us.
    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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