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    Clinical Trial Results:
    Probiotic Treatment of Ulcerative Colitis with Trichuris suis ova (TSO)

    Summary
    EudraCT number
    		 2017-004772-65
    Trial protocol
    		 DK  
    Global end of trial date
    10 Jan 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    31 Dec 2022
    First version publication date
    31 Dec 2022
    Other versions
    Summary report(s)
    		 PROCTO study Summary

    Trial information

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    Trial identification
    Sponsor protocol code
    PROCTO
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03565939
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    ParaTech A/S
    Sponsor organisation address
    Dr. Neergaards Vej 3, Hoersholm, Denmark, 2970
    Public contact
    Christian Kapel CEO, Professor, PhD, ParaTech A/S, +45 22966270, chk@para-tech.dk
    Scientific contact
    Hanne Kapel CMO, MSc Pharm, ParaTech A/S, +45 22172480, hsk@para-tech.dk
    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 Oct 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    10 Jan 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Jan 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objectives of the present “PROCTO” trial is to demonstrate that administration of 7500 TSO every second week over 24 weeks will reduce the intestinal inflammation in moderate Ulcerative Colitis (UC) by achieving clinical remission by full Mayo disease score (primary endpoint).
    Protection of trial subjects
    All study participants were required to read a Subject Information Sheet and to read and sign an Informed Consent Form and Power of Attorney.
    Background therapy
    		 No treatment or if treated with 5-Aminosalicyl acid (5-ASA): 5-ASA ≥ 8 weeks with a stable dose for at least 4 weeks both oral and rectal use.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    04 May 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
    Denmark: 119
    Worldwide total number of subjects
    119
    EEA total number of subjects
    119
    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)
    110
    From 65 to 84 years
    9
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The trial took place from May 4 2018 to January 10 2022 at: • Hvidovre Hospital, Kettegaard Allé 30, 2650 Hvidovre, Denmark The inclusion of patients were mainly referred from: • Hvidovre Hospital, Denmark • Herlev Hospital, Denmark • Bispebjerg Hospital, Denmark

    Pre-assignment
    Screening details
    		 Participants (18-75 years) with a diagnosis (diagnosed >3 months prior to inclusion and tapered down from last oral steroid ≥4 weeks prior to inclusion) of moderately active ulcerative colitis (UC) were enrolled in a 1:1 ratio to receive TSO or placebo.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    The TSO has no taste, smell, appearance, or immediate effect, which is different from that of the placebo product, and the participants drank directly from an opaque brown bottle (under sub-investigator observation) to ensure that it was impossible to differentiate between TSO and placebo. To ensure blinding throughout the trial, the laboratory parameters mentioned below were blinded until the end of the trial: Trichuris suis specific IgG and IgE Eosinophils Leucocytes

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 7500 TSO
    Arm description
    		 The patients received the 7500 TSO orally as a single administration every 2 weeks for 24 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TSO 7500
    Investigational medicinal product code
    Other name
    TSO
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    One dose consisted of 15 ml sulphuric acid H2SO4 pH1 suspension with 7500 embryonated, viable and active TSO (as active ingredient) neutralised with 4.2 ml neutralization solution (saturated sodiumhydrogen-carbonat (NaHCO3)). TSO was administrated on an “empty stomach” i.e. no meal later than 4 hours before receiving the TSO treatment.

    Arm title
    		 Placebo
    Arm description
    		 The patients received placebo orally as a single administration every 2 weeks for 24 weeks
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Placebo
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    One dose consisted of 15 ml sulphuric acid H2SO4 pH1 suspension neutralised with 4.2 ml neutralization solution (saturated sodiumhydrogen-carbonat (NaHCO3)). The placebo was administered on an “empty stomach” i.e. no meal later than 4 hours before receiving the placebo treatment.

    Number of subjects in period 1
    		7500 TSO Placebo
    Started
    60
    59
    Week 12
    55
    56
    Week 14
    54
    53
    Week 16
    49
    52
    Week 18
    44
    50
    Week 20
    43
    46
    Week 22
    42
    42
    Week 24
    42
    41
    Completed
    42
    41
    Not completed
    18
    18
         UC aggravation
    17
    18
         Suspected pregnancy
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    7500 TSO
    Reporting group description
    		 The patients received the 7500 TSO orally as a single administration every 2 weeks for 24 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 The patients received placebo orally as a single administration every 2 weeks for 24 weeks

    Reporting group values
    		 7500 TSO Placebo Total
    Number of subjects
    		 60 59 119
    Age categorical
    Units: Subjects
        Adults (18-75 years)
    		 60 59 119
    Gender categorical
    Units: Subjects
        Female
    		 33 28 61
        Male
    		 27 31 58
    Subject analysis sets

    Subject analysis set title
    ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomised patients.

    Subject analysis set title
    PP
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients that did not receive steroid at least 12 weeks prior to analysis.

    Subject analysis set title
    CSF
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Complete steroid free (CSF). Patients that did not receive steroid during the study period.

    Subject analysis sets values
    		 ITT PP CSF
    Number of subjects
    119
    83
    60
    Age categorical
    Units: Subjects
        Adults (18-75 years)
    119
    83
    60
    Age continuous
    Units:
        
    ±
    ±
    ±
    Gender categorical
    Units: Subjects
        Female
    61
    45
    35
        Male
    58
    38
    25

    End points

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    End points reporting groups
    Reporting group title
    7500 TSO
    Reporting group description
    		 The patients received the 7500 TSO orally as a single administration every 2 weeks for 24 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 The patients received placebo orally as a single administration every 2 weeks for 24 weeks

    Subject analysis set title
    ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomised patients.

    Subject analysis set title
    PP
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients that did not receive steroid at least 12 weeks prior to analysis.

    Subject analysis set title
    CSF
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Complete steroid free (CSF). Patients that did not receive steroid during the study period.

    Primary: No. 1: To achieve clinical remission defined as full Mayo score ≤ 2 at 24 weeks (long-term efficacy) (ITT)

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    End point title
    		 No. 1: To achieve clinical remission defined as full Mayo score ≤ 2 at 24 weeks (long-term efficacy) (ITT)
    End point description
    Percentage of participants who achieved clinical remission defined as full Mayo score ≤ 2 at 24 weeks or withdrawal. Clinical remission was defined as a complete Mayo score of ≤2 points. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
    End point type
    Primary
    End point timeframe
    Week 24 or withdrawal.
    End point values
    		 7500 TSO Placebo ITT
    Number of subjects analysed
    60
    59
    119
    Units: Full Mayo score 0-12
    18
    20
    38
    Statistical analysis title
    		 Clinical remission ITT (Chi-squared)
    Statistical analysis description
    Chi-squared test is used to test the difference between the proportion of patients in the TSO and placebo group, who reached the endpoint.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.795
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 1.5

    Primary: No. 1: To achieve clinical remission defined as full Mayo score ≤ 2 at 24 weeks (long-term efficacy) (PP)

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    End point title
    		 No. 1: To achieve clinical remission defined as full Mayo score ≤ 2 at 24 weeks (long-term efficacy) (PP)
    End point description
    Percentage of participants who achieved clinical remission defined as full Mayo score ≤ 2 at 24 weeks or withdrawal. Clinical remission was defined as a complete Mayo score of ≤2 points. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
    End point type
    Primary
    End point timeframe
    Week 24 or withdrawal
    End point values
    		 7500 TSO Placebo PP
    Number of subjects analysed
    43
    40
    83
    Units: Full Mayo score 0-12
    17
    17
    34
    Statistical analysis title
    		 Clinical remission PP (Chi-squared)
    Statistical analysis description
    Chi-squared test is used to test the difference between the proportion of patients in the TSO and placebo group, who reached the endpoint.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.959
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 1.56

    Secondary: No. 2: To achieve reduction of full Mayo score of 4 or more steps at 24 weeks (ITT)

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    End point title
    		 No. 2: To achieve reduction of full Mayo score of 4 or more steps at 24 weeks (ITT)
    End point description
    Percentage of participants who achieved reduction of full Mayo score of 4 or more steps at 24 weeks or withdrawal. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
    End point type
    Secondary
    End point timeframe
    Week 24 or withdrawal.
    End point values
    		 7500 TSO Placebo ITT
    Number of subjects analysed
    60
    59
    119
    Units: Full Mayo 0-12
    24
    24
    48
    Statistical analysis title
    		 Reduction of full Mayo score ITT (Chi-squared)
    Statistical analysis description
    Chi-squared test is used to test the difference between the proportion of patients in the TSO and placebo group, who reached the endpoint.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 1
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 1.52

    Secondary: No. 2: To achieve reduction of full Mayo score of 4 or more steps at 24 weeks (PP)

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    End point title
    		 No. 2: To achieve reduction of full Mayo score of 4 or more steps at 24 weeks (PP)
    End point description
    Percentage of participants who achieved reduction of full Mayo score of 4 or more steps at 24 weeks or withdrawal. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 7500 TSO Placebo PP
    Number of subjects analysed
    43
    40
    83
    Units: Full Mayo score 0-12
    23
    20
    43
    Statistical analysis title
    		 Reduction of full Mayo score PP (Chi-squared)
    Statistical analysis description
    Chi-squared test is used to test the difference between the proportion of patients in the TSO and placebo group, who reached the endpoint.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.922
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.62

    Secondary: No. 2: To achieve reduction of full Mayo score of 4 or more steps at 24 weeks (CSF)

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    End point title
    		 No. 2: To achieve reduction of full Mayo score of 4 or more steps at 24 weeks (CSF)
    End point description
    Percentage of participants who achieved reduction of full Mayo score of 4 or more steps at 24 weeks or withdrawal. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
    End point type
    Secondary
    End point timeframe
    Week 24 or withdrawal.
    End point values
    		 7500 TSO Placebo CSF
    Number of subjects analysed
    33
    27
    60
    Units: Full Mayo score 0-12
    16
    11
    27
    Statistical analysis title
    		 Reduction of full Mayo score CSF (Chi-squared)
    Statistical analysis description
    Chi-squared test is used to test the difference between the proportion of patients in the TSO and placebo group, who reached the endpoint.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.735
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 2.11

    Secondary: No. 3: Complete steroid free clinical remission defined as full Mayo score ≤ 2 at 24 weeks

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    End point title
    		 No. 3: Complete steroid free clinical remission defined as full Mayo score ≤ 2 at 24 weeks
    End point description
    Percentage of participants who achieved clinical remission defined as full Mayo score ≤ 2 at 24 weeks or withdrawal. Clinical remission was defined as a complete Mayo score of ≤2 points. The Mayo score was a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consisted of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
    End point type
    Secondary
    End point timeframe
    Week 24 or withdrawal.
    End point values
    		 7500 TSO Placebo CSF
    Number of subjects analysed
    33
    27
    60
    Units: Full Mayo score 0-12
    13
    9
    22
    Statistical analysis title
    		 Clinical remission CSF (Chi-squared)
    Statistical analysis description
    Chi-squared test is used to test the difference between the proportion of patients in the TSO and placebo group, who reached the endpoint.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.829
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 2.33

    Secondary: No. 4: Endoscopic remission defined as mucosal appearance Mayo sub-score of 0 or 1 at 24 weeks (ITT)

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    End point title
    		 No. 4: Endoscopic remission defined as mucosal appearance Mayo sub-score of 0 or 1 at 24 weeks (ITT)
    End point description
    Percentage of participants who achieved endoscopic remission defined as mucosal appearance Mayo sub-score of 0 or 1 at 24 weeks or withdrawal.
    End point type
    Secondary
    End point timeframe
    Week 24 or withdrawal.
    End point values
    		 7500 TSO Placebo ITT
    Number of subjects analysed
    59
    58
    117
    Units: Endoscopy subscore 0-3
    26
    25
    51
    Statistical analysis title
    		 Endoscopic remission ITT (Chi-squared)
    Statistical analysis description
    Chi-squared test is used to test the difference between the proportion of patients in the TSO and placebo group, who reached the endpoint.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 1
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 1.54

    Secondary: No. 4: Endoscopic remission defined as mucosal appearance Mayo sub-score of 0 or 1 at 24 weeks (PP)

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    End point title
    		 No. 4: Endoscopic remission defined as mucosal appearance Mayo sub-score of 0 or 1 at 24 weeks (PP)
    End point description
    Percentage of participants who achieved endoscopic remission defined as mucosal appearance Mayo sub-score of 0 or 1 at 24 weeks or withdrawal.
    End point type
    Secondary
    End point timeframe
    Week 24 or withdrawal.
    End point values
    		 7500 TSO Placebo PP
    Number of subjects analysed
    43
    40
    83
    Units: Endoscopy subscore 0-3
    24
    20
    44
    Statistical analysis title
    		 Endoscopic remission PP (Chi-squared)
    Statistical analysis description
    Chi-squared test is used to test the difference between the proportion of patients in the TSO and placebo group, who reached the endpoint.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.756
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.68

    Secondary: No. 4: Endoscopic remission defined as mucosal appearance Mayo sub-score of 0 or 1 at 24 weeks (CSF)

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    End point title
    		 No. 4: Endoscopic remission defined as mucosal appearance Mayo sub-score of 0 or 1 at 24 weeks (CSF)
    End point description
    Percentage of participants who achieved endoscopic remission defined as mucosal appearance Mayo sub-score of 0 or 1 at 24 weeks or withdrawal.
    End point type
    Secondary
    End point timeframe
    Week 24 or withdrawal.
    End point values
    		 7500 TSO Placebo CSF
    Number of subjects analysed
    33
    27
    60
    Units: Endoscopy subscore 0-3
    19
    11
    30
    Statistical analysis title
    		 Endoscopic remission CSF (Chi-squared)
    Statistical analysis description
    Chi-squared test is used to test the difference between the proportion of patients in the TSO and placebo group, who reached the endpoint.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.299
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 2.43

    Secondary: No. 5: Symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 at 12 weeks and 24 weeks / WD (ITT)

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    End point title
    		 No. 5: Symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 at 12 weeks and 24 weeks / WD (ITT)
    End point description
    Percentage of participants who achieved symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 at 12 weeks and 24 weeks or withdrawal (WD).
    End point type
    Secondary
    End point timeframe
    Week 12 and 24 or withdrawal (WD).
    End point values
    		 7500 TSO Placebo ITT
    Number of subjects analysed
    60
    59
    119
    Units: Mayo subscores 0-3
    27
    22
    49
    Statistical analysis title
    		 Symptomatic remission at 12 weeks ITT (Chi^2)
    Statistical analysis description
    Chi-squared test is used to test the difference between the proportion of patients in the TSO and placebo group, who reached the endpoint.
    Comparison groups
    Placebo v 7500 TSO
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.145
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1.81
    Statistical analysis title
    		 Symptomatic remission at 24 weeks/WD ITT (Chi^2)
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.504
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.86

    Secondary: No. 5: Symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 at 12 weeks and 24 weeks / WD (PP)

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    End point title
    		 No. 5: Symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 at 12 weeks and 24 weeks / WD (PP)
    End point description
    Percentage of participants who achieved symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 at week 12 and 24 or withdrawal.
    End point type
    Secondary
    End point timeframe
    Week 12 and 24 or withdrawal (WD).
    End point values
    		 7500 TSO Placebo PP
    Number of subjects analysed
    43
    40
    83
    Units: Mayo subscore 0-3
    25
    18
    43
    Statistical analysis title
    		 Symptomatic remission week 12 PP (Chi-squared)
    Statistical analysis description
    Chi-squared test is used to test the difference between the proportion of patients in the TSO and placebo group, who reached the endpoint.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.065
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.01
         upper limit
    		 2
    Statistical analysis title
    		 Symptomatic remission week 24/WD PP (Chi-squared)
    Statistical analysis description
    Chi-squared test is used to test the difference between the proportion of patients in the TSO and placebo group, who reached the endpoint.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.328
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.98

    Secondary: No. 5: Symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 at 12 weeks and 24 weeks / WD (CSF)

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    End point title
    		 No. 5: Symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 at 12 weeks and 24 weeks / WD (CSF)
    End point description
    Percentage of participants who achieved symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 at week 12 and 24 or withdrawal (WD).
    End point type
    Secondary
    End point timeframe
    Week 12 and 24 or withdrawal (WD).
    End point values
    		 7500 TSO Placebo CSF
    Number of subjects analysed
    33
    27
    60
    Units: Mayo subscores 0-3
    19
    11
    30
    Statistical analysis title
    		 Symptomatic remission week 12 CSF (Chi-squared)
    Statistical analysis description
    Chi-squared test is used to test the difference between the proportion of patients in the TSO and placebo group, who reached the endpoint.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.011
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    2.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.17
         upper limit
    		 3.73
    Statistical analysis title
    		 Symptomatic remission week 24/WD CSF (Chi-squared)
    Statistical analysis description
    Chi-squared test is used to test the difference between the proportion of patients in the TSO and placebo group, who reached the endpoint.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.299
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 2.43

    Secondary: No. 6: Time to achieve remission defined as time to achieve a pMayo score ≤ 1 (0-24 weeks) (ITT)

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    End point title
    		 No. 6: Time to achieve remission defined as time to achieve a pMayo score ≤ 1 (0-24 weeks) (ITT)
    End point description
    Time to achieve pMayo remission defined as time to achieve a pMayo score ≤ 1 (0-24 weeks). The index consisted of 3 subscores: rectal bleeding, stool frequency, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete pMayo score ranges from 0 to 9 (higher scores indicate greater disease activity).
    End point type
    Secondary
    End point timeframe
    0-13 visits (0-24 weeks)
    End point values
    		 7500 TSO Placebo ITT
    Number of subjects analysed
    60
    59
    119
    Units: Time (0-13 visits)
    32
    36
    68
    Attachments
    		 Plot 6 Time to pMayo remission (visit no.)
    Statistical analysis title
    		 Time to achieve remission ITT (Wilcoxon-test)
    Statistical analysis description
    Difference in mean remission times for active and placebo is tested by t-test. Wilcoxon sum-rank test will be used instead of t-test if the normality assumption cannot be satisfied, Normality assumption of data will be evaluated by QQ-plots.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Median difference (final values)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 3

    Secondary: No. 6: Time to achieve remission defined as time to achieve a pMayo score ≤ 1 (0-24 weeks) (PP)

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    End point title
    		 No. 6: Time to achieve remission defined as time to achieve a pMayo score ≤ 1 (0-24 weeks) (PP)
    End point description
    Time to achieve pMayo remission defined as time to achieve a pMayo score ≤ 1 (0-24 weeks). The index consisted of 3 subscores: rectal bleeding, stool frequency, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete pMayo score ranges from 0 to 9 (higher scores indicate greater disease activity).
    End point type
    Secondary
    End point timeframe
    0-13 visits (0-24 weeks)
    End point values
    		 7500 TSO Placebo PP
    Number of subjects analysed
    43
    40
    83
    Units: Time (0-13 visits)
    30
    26
    56
    Statistical analysis title
    		 Time to achieve remission PP (Wilcoxon-test)
    Statistical analysis description
    Difference in mean remission times for active and placebo is tested by t-test. Wilcoxon sum-rank test will be used instead of t-test if the normality assumption cannot be satisfied, Normality assumption of data will be evaluated by QQ-plots.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.785
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Median difference (final values)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 2

    Secondary: No. 6: Time to achieve remission defined as time to achieve a pMayo score ≤ 1 (0-24 weeks) (CSF)

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    End point title
    		 No. 6: Time to achieve remission defined as time to achieve a pMayo score ≤ 1 (0-24 weeks) (CSF)
    End point description
    Time to achieve pMayo remission defined as time to achieve a pMayo score ≤ 1 (0-24 weeks). The index consisted of 3 subscores: rectal bleeding, stool frequency, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete pMayo score ranges from 0 to 9 (higher scores indicate greater disease activity).
    End point type
    Secondary
    End point timeframe
    0-13 visits (0-24 weeks)
    End point values
    		 7500 TSO Placebo CSF
    Number of subjects analysed
    33
    27
    60
    Units: Time (0-13 visits)
    20
    14
    34
    Statistical analysis title
    		 Time to achieve remission CSF (Wilcoxon-test)
    Statistical analysis description
    Difference in mean remission times for active and placebo is tested by t-test. Wilcoxon sum-rank test will be used instead of t-test if the normality assumption cannot be satisfied, Normality assumption of data will be evaluated by QQ-plots.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.282
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Median difference (final values)
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 2

    Secondary: No. 7: Time to achieve symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 (0-24 weeks) (ITT)

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    End point title
    		 No. 7: Time to achieve symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 (0-24 weeks) (ITT)
    End point description
    Time to achieve symptomatic remission defined as stool frequency Mayo sub- score of 0 or 1 and rectal bleeding Mayo sub-score of 0 (0-24 weeks)
    End point type
    Secondary
    End point timeframe
    0-13 visits (0-24 weeks)
    End point values
    		 7500 TSO Placebo ITT
    Number of subjects analysed
    60
    59
    119
    Units: Time (0-13 visits)
    39
    38
    77
    Attachments
    		 Plot Time to symptomatic remission (visit no.)
    Statistical analysis title
    		 Time to achieve symptomatic remission ITT Wilcoxon
    Statistical analysis description
    Difference in mean symptomatic remission times for active and placebo is tested by t-test. Wilcoxon sum-rank test will be used instead of t-test if the normality assumption cannot be satisfied, Normality assumption of data will be evaluated by QQ-plots.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.594
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Median difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 2

    Secondary: No. 7: Time to achieve symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 (0-24 weeks) (PP)

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    End point title
    		 No. 7: Time to achieve symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 (0-24 weeks) (PP)
    End point description
    Time to achieve symptomatic remission defined as stool frequency Mayo sub- score of 0 or 1 and rectal bleeding Mayo sub-score of 0 (0-24 weeks).
    End point type
    Secondary
    End point timeframe
    0-13 visits (0-24 weeks)
    End point values
    		 7500 TSO Placebo PP
    Number of subjects analysed
    43
    40
    83
    Units: Time (0-13 visits)
    34
    28
    62
    Statistical analysis title
    		 Time to achieve symptomatic remission PP Wilcoxon
    Statistical analysis description
    Difference in mean symptomatic remission times for active and placebo is tested by t-test. Wilcoxon sum-rank test will be used instead of t-test if the normality assumption cannot be satisfied, Normality assumption of data will be evaluated by QQ-plots.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.72
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Median difference (final values)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 3

    Secondary: No. 7: Time to achieve symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 (0-24 weeks) (CSF)

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    End point title
    		 No. 7: Time to achieve symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 (0-24 weeks) (CSF)
    End point description
    Time to achieve symptomatic remission defined as stool frequency Mayo sub- score of 0 or 1 and rectal bleeding Mayo sub-score of 0 (0-24 weeks)
    End point type
    Secondary
    End point timeframe
    0-13 visits (0-24 weeks)
    End point values
    		 7500 TSO Placebo CSF
    Number of subjects analysed
    33
    27
    60
    Units: Time (0-13 visits)
    24
    15
    39
    Statistical analysis title
    		 Time to achieve symptomatic remission CSF Wilcoxon
    Statistical analysis description
    Difference in mean symptomatic remission times for active and placebo is tested by t-test. Wilcoxon sum-rank test will be used instead of t-test if the normality assumption cannot be satisfied, Normality assumption of data will be evaluated by QQ-plots.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.268
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Median difference (final values)
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 2

    Secondary: No. 8: Time to achieve response defined as time to achieve reduction in pMayo score of 3 or more steps (0-24 weeks) (ITT)

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    End point title
    		 No. 8: Time to achieve response defined as time to achieve reduction in pMayo score of 3 or more steps (0-24 weeks) (ITT)
    End point description
    Time to achieve response defined as time to achieve reduction in pMayo score of 3 or more steps (0-24 weeks)
    End point type
    Secondary
    End point timeframe
    0-13 visits (0-24 weeks)
    End point values
    		 7500 TSO Placebo ITT
    Number of subjects analysed
    60
    59
    119
    Units: Time (0-13 visits)
    48
    43
    91
    Attachments
    		 Plot Time to achieve response (visit no.)
    Statistical analysis title
    		 Time to achieve response ITT (Wilcoxon-test)
    Statistical analysis description
    Difference in mean response times for active and placebo is tested by t-test. Wilcoxon sum-rank test will be used instead of t-test if the normality assumption cannot be satisfied, Normality assumption of data will be evaluated by QQ-plots.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.186
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Median difference (final values)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 2

    Secondary: No. 8: Time to achieve response defined as time to achieve reduction in pMayo score of 3 or more steps (0-24 weeks) (PP)

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    End point title
    		 No. 8: Time to achieve response defined as time to achieve reduction in pMayo score of 3 or more steps (0-24 weeks) (PP)
    End point description
    Time to achieve response defined as time to achieve reduction in pMayo score of 3 or more steps (0-24 weeks)
    End point type
    Secondary
    End point timeframe
    0-13 visits (0-24 weeks)
    End point values
    		 7500 TSO Placebo PP
    Number of subjects analysed
    43
    40
    83
    Units: Time (0-13 visits)
    38
    29
    67
    Statistical analysis title
    		 Time to achieve response PP (Wilcoxon-test)
    Statistical analysis description
    Difference in mean response times for active and placebo is tested by t-test. Wilcoxon sum-rank test will be used instead of t-test if the normality assumption cannot be satisfied, Normality assumption of data will be evaluated by QQ-plots.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.243
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Median difference (final values)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 2

    Secondary: No. 8: Time to achieve response defined as time to achieve reduction in pMayo score of 3 or more steps (0-24 weeks) (CSF)

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    End point title
    		 No. 8: Time to achieve response defined as time to achieve reduction in pMayo score of 3 or more steps (0-24 weeks) (CSF)
    End point description
    Time to achieve response defined as time to achieve reduction in pMayo score of 3 or more steps (0-24 weeks)
    End point type
    Secondary
    End point timeframe
    0-13 visits (0-24 weeks)
    End point values
    		 7500 TSO Placebo CSF
    Number of subjects analysed
    33
    27
    60
    Units: Time (0-13 visits)
    28
    17
    45
    Statistical analysis title
    		 Time to achieve response CSF (Wilcoxon-test)
    Statistical analysis description
    Difference in mean response times for active and placebo is tested by t-test. Wilcoxon sum-rank test will be used instead of t-test if the normality assumption cannot be satisfied, Normality assumption of data will be evaluated by QQ-plots.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.705
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Median difference (final values)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 3

    Secondary: No. 9: Difference between placebo and TSO in change in disease severity assessed by pMayo scores over time from week 12 to 24 or withdrawal (ITT) Mixed Models Analysis

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    End point title
    		 No. 9: Difference between placebo and TSO in change in disease severity assessed by pMayo scores over time from week 12 to 24 or withdrawal (ITT) Mixed Models Analysis
    End point description
    pMayo score consisted of 3 subscores: rectal bleeding, stool frequency, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete pMayo score ranges from 0 to 9 (higher scores indicate greater disease activity). WD visit data is allocated the visit immediately after the last visit before withdrawal. I.e., a pMayo score from a WD visit between week 10 and week 12 is allocated pMayo week 12.
    End point type
    Secondary
    End point timeframe
    Week 12 to 24 or withdrawal (WD).
    End point values
    		 7500 TSO Placebo ITT
    Number of subjects analysed
    60
    59
    119
    Units: pMayo score 0-9
    55
    56
    111
    Attachments
    		 Mean pMayo over time. *p<0.05
    Statistical analysis title
    		 Difference in pMayo over time week 12-24/WD (ITT)
    Statistical analysis description
    Difference in mean pMayo score over time between active and placebo group are analyzed by mixed linear regression model. The fixed effect terms in the model will be: Active/placebo, visit number and interaction between the two.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.07
    Method
    		 Mixed models analysis
    Confidence interval

    Secondary: No. 9: Difference between placebo and TSO in change in disease severity assessed by pMayo scores over time from week 12 to 24 or withdrawal (PP) Mixed Models Analysis

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    End point title
    		 No. 9: Difference between placebo and TSO in change in disease severity assessed by pMayo scores over time from week 12 to 24 or withdrawal (PP) Mixed Models Analysis
    End point description
    pMayo score consisted of 3 subscores: rectal bleeding, stool frequency, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete pMayo score ranges from 0 to 9 (higher scores indicate greater disease activity). WD visit data is allocated the visit immediately after the last visit before withdrawal. I.e., a pMayo score from a WD visit between week 10 and week 12 is allocated pMayo week 12.
    End point type
    Secondary
    End point timeframe
    Week 12 to 24 or withdrawal.
    End point values
    		 7500 TSO Placebo PP
    Number of subjects analysed
    43
    40
    83
    Units: pMayo score 0-9
    43
    40
    83
    Statistical analysis title
    		 Difference in pMayo over time week 12-24/WD (PP)
    Statistical analysis description
    Difference in mean pMayo score over time between active and placebo group are analyzed by mixed linear regression model. The fixed effect terms in the model will be: Active/placebo, visit number and interaction between the two.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.104
    Method
    		 Mixed models analysis
    Confidence interval

    Secondary: No. 9: Difference between placebo and TSO in change in disease severity assessed by pMayo scores over time from week 12 to 24 or withdrawal (CSF) Mixed Models Analysis

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    End point title
    		 No. 9: Difference between placebo and TSO in change in disease severity assessed by pMayo scores over time from week 12 to 24 or withdrawal (CSF) Mixed Models Analysis
    End point description
    pMayo score consisted of 3 subscores: rectal bleeding, stool frequency, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete pMayo score ranges from 0 to 9 (higher scores indicate greater disease activity). WD visit data is allocated the visit immediately after the last visit before withdrawal. I.e., a pMayo score from a WD visit between week 10 and week 12 is allocated pMayo week 12.
    End point type
    Secondary
    End point timeframe
    Week 12 to 24 or withdrawal.
    End point values
    		 7500 TSO Placebo CSF
    Number of subjects analysed
    33
    27
    60
    Units: pMayo score 0-9
    33
    27
    60
    Statistical analysis title
    		 Difference in pMayo over time week 12-24/WD (CSF)
    Statistical analysis description
    Difference in mean pMayo score over time between active and placebo group are analyzed by mixed linear regression model. The fixed effect terms in the model will be: Active/placebo, visit number and interaction between the two.
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.129
    Method
    		 Mixed models analysis
    Confidence interval

    Secondary: No. 9: Difference between placebo and TSO in change in disease severity assessed by pMayo scores over time from week 12 to 24 or withdrawal (ITT) (Chi-Squared)

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    End point title
    		 No. 9: Difference between placebo and TSO in change in disease severity assessed by pMayo scores over time from week 12 to 24 or withdrawal (ITT) (Chi-Squared)
    End point description
    pMayo score consisted of 3 subscores: rectal bleeding, stool frequency, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete pMayo score ranges from 0 to 9 (higher scores indicate greater disease activity). WD visit data is allocated the visit immediately after the last visit before withdrawal. I.e., a pMayo score from a WD visit between week 10 and week 12 is allocated pMayo week 12.
    End point type
    Secondary
    End point timeframe
    Week 12 to 24 or withdrawal.
    End point values
    		 7500 TSO Placebo ITT
    Number of subjects analysed
    60
    59
    119
    Units: pMayo score 0-9
    55
    56
    111
    Statistical analysis title
    		 Difference in pMayo week 24/WD (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.326
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.46
         upper limit
    		 1.21
    Statistical analysis title
    		 Difference in pMayo week 12 (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.785
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.73
    Statistical analysis title
    		 Difference in pMayo week 14 (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.492
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.83
    Statistical analysis title
    		 Difference in pMayo week 16 (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.142
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.93
         upper limit
    		 2.27
    Statistical analysis title
    		 Difference in pMayo week 18 (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.012
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.15
         upper limit
    		 2.53
    Statistical analysis title
    		 Difference in pMayo week 20 (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.446
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 1.8
    Statistical analysis title
    		 Difference in pMayo week 22 (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 1
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.42

    Secondary: No. 9: Difference between placebo and TSO in change in disease severity assessed by pMayo scores over time from week 12 to 24 or withdrawal (PP) (Chi-Squared)

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    End point title
    		 No. 9: Difference between placebo and TSO in change in disease severity assessed by pMayo scores over time from week 12 to 24 or withdrawal (PP) (Chi-Squared)
    End point description
    pMayo score consisted of 3 subscores: rectal bleeding, stool frequency, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete pMayo score ranges from 0 to 9 (higher scores indicate greater disease activity). WD visit data is allocated the visit immediately after the last visit before withdrawal. I.e., a pMayo score from a WD visit between week 10 and week 12 is allocated pMayo week 12.
    End point type
    Secondary
    End point timeframe
    Week 12 to 24 or withdrawal (WD)
    End point values
    		 7500 TSO Placebo PP
    Number of subjects analysed
    43
    40
    83
    Units: pMayo score 0-9
    43
    40
    83
    Statistical analysis title
    		 Difference in pMayo week 24/WD PP (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.273
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 1.18
    Statistical analysis title
    		 Difference in pMayo week 12 PP (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.435
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 1.98
    Statistical analysis title
    		 Difference in pMayo week 14 PP (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.234
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 2.04
    Statistical analysis title
    		 Difference in pMayo week 16 PP (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.124
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.94
         upper limit
    		 2.31
    Statistical analysis title
    		 Difference in pMayo week 18 PP (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.075
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 2.12
    Statistical analysis title
    		 Difference in pMayo week 20 PP (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.847
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.72
         upper limit
    		 1.65
    Statistical analysis title
    		 Difference in pMayo week 22 PP (Chi-squared)
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.987
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.72
         upper limit
    		 1.54

    Secondary: No. 9: Difference between placebo and TSO in change in disease severity assessed by pMayo scores over time from week 12 to 24 or withdrawal (CSF) (Chi-Squared)

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    End point title
    		 No. 9: Difference between placebo and TSO in change in disease severity assessed by pMayo scores over time from week 12 to 24 or withdrawal (CSF) (Chi-Squared)
    End point description
    pMayo score consisted of 3 subscores: rectal bleeding, stool frequency, and physician's global assessment. Each subscore was scored on a scale from 0 to 3 and the complete pMayo score ranges from 0 to 9 (higher scores indicate greater disease activity). WD visit data is allocated the visit immediately after the last visit before withdrawal. I.e., a pMayo score from a WD visit between week 10 and week 12 is allocated pMayo week 12.
    End point type
    Secondary
    End point timeframe
    Week 12 to 24 or withdrawal (WD)
    End point values
    		 7500 TSO Placebo CSF
    Number of subjects analysed
    33
    27
    60
    Units: pMayo score 0-9
    33
    27
    60
    Statistical analysis title
    		 Difference in pMayo week 24/WD CSF (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.913
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 1.66
    Statistical analysis title
    		 Difference in pMayo week 12 CSF (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.089
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    2.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 5.55
    Statistical analysis title
    		 Difference in pMayo week 14 CSF (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.048
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.03
         upper limit
    		 4.28
    Statistical analysis title
    		 Difference in pMayo week 16 CSF (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.101
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.94
         upper limit
    		 3.91
    Statistical analysis title
    		 Difference in pMayo week 18 CSF (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.023
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.11
         upper limit
    		 3.95
    Statistical analysis title
    		 Difference in pMayo week 20 CSF (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 1
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 2
    Statistical analysis title
    		 Difference in pMayo week 22 CSF (Chi-squared)
    Statistical analysis description
    Difference in remission yes/no in active vs. placebo group is tested by chi-squared test for each week 12-24 or withdrawal (WD).
    Comparison groups
    7500 TSO v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.396
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 2.2

    Other pre-specified: Evaluation of blood eosinophils

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    End point title
    		 Evaluation of blood eosinophils
    End point description
    End point type
    Other pre-specified
    End point timeframe
    0-24 weeks or withdrawal
    End point values
    		 7500 TSO Placebo ITT
    Number of subjects analysed
    60
    59
    119
    Units: 10^9 cells/L
    60
    59
    119
    Attachments
    		 Blood eosinophils in placebo and TSO w/wo steroid
    No statistical analyses for this end point

    Post-hoc: Symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 over time at 0-24 weeks / WD (ITT)

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    End point title
    		 Symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 over time at 0-24 weeks / WD (ITT)
    End point description
    Percentage of participants who achieved symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 at 0 weeks to 24 weeks or withdrawal (WD).
    End point type
    Post-hoc
    End point timeframe
    0-24 weeks or withdrawal
    End point values
    		 7500 TSO Placebo ITT PP CSF
    Number of subjects analysed
    60
    59
    119
    83
    60
    Units: Mayo subscores 0-3
    25
    22
    47
    42
    29
    Attachments
    		 Probability plot of symptomatic remission. *p<0.05
    No statistical analyses for this end point

    Post-hoc: Patient-reported outcome IBD disability index

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    End point title
    		 Patient-reported outcome IBD disability index
    End point description
    IBD score will be calculated based on the sum of responds item values. Values are generated for each item ranging from 0-4, the sum is then rescaled to a range 0- 100 based on the amount of answered items.
    End point type
    Post-hoc
    End point timeframe
    0-24 weeks or withdrawal
    End point values
    		 7500 TSO Placebo
    Number of subjects analysed
    60
    59
    Units: IBD score
    60
    59
    Attachments
    		 Patients questionnaires IBD disability index
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 0 to day 210 (+/-7 days).
    Adverse event reporting additional description
    At each visit investigator document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by participant or observed by investigator was recorded, irrespective of relation to study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    7500 TSO
    Reporting group description
    		 The patients received the 7500 TSO orally as a single administration every 2 weeks for 24 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 The patients received placebo orally as a single administration every 2 weeks for 24 weeks

    Serious adverse events
    		 7500 TSO Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 60 (20.00%)
    11 / 59 (18.64%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Clavicle fracture
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic inflammatory demyelinating polyradiculoneuropathy
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Diplopia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ulcerative
    Additional description: Aggravation of UC
         subjects affected / exposed
    7 / 60 (11.67%)
    4 / 59 (6.78%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 60 (0.00%)
    2 / 59 (3.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 7500 TSO Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    56 / 60 (93.33%)
    55 / 59 (93.22%)
    Cardiac disorders
    Dizziness
         subjects affected / exposed
    0 / 60 (0.00%)
    4 / 59 (6.78%)
         occurrences all number
    0
    4
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 60 (1.67%)
    9 / 59 (15.25%)
         occurrences all number
    1
    9
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 60 (3.33%)
    4 / 59 (6.78%)
         occurrences all number
    2
    4
    Gastrointestinal disorders
    Colitis ulcerative
    Additional description: Aggravation of UC
         subjects affected / exposed
    26 / 60 (43.33%)
    31 / 59 (52.54%)
         occurrences all number
    33
    37
    Abdominal distension
         subjects affected / exposed
    28 / 60 (46.67%)
    23 / 59 (38.98%)
         occurrences all number
    48
    33
    Constipation
         subjects affected / exposed
    8 / 60 (13.33%)
    4 / 59 (6.78%)
         occurrences all number
    9
    4
    Diarrhea
         subjects affected / exposed
    28 / 60 (46.67%)
    16 / 59 (27.12%)
         occurrences all number
    33
    30
    Dyspepsia
         subjects affected / exposed
    3 / 60 (5.00%)
    2 / 59 (3.39%)
         occurrences all number
    3
    3
    Flatulence
         subjects affected / exposed
    10 / 60 (16.67%)
    6 / 59 (10.17%)
         occurrences all number
    10
    6
    Nausea
         subjects affected / exposed
    5 / 60 (8.33%)
    5 / 59 (8.47%)
         occurrences all number
    7
    5
    Oropharyngeal pain
         subjects affected / exposed
    5 / 60 (8.33%)
    1 / 59 (1.69%)
         occurrences all number
    7
    1
    Vomiting
         subjects affected / exposed
    4 / 60 (6.67%)
    4 / 59 (6.78%)
         occurrences all number
    4
    4
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    5 / 60 (8.33%)
    9 / 59 (15.25%)
         occurrences all number
    5
    10
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    7 / 60 (11.67%)
    4 / 59 (6.78%)
         occurrences all number
    8
    5
    Upper respiratory tract infection
         subjects affected / exposed
    8 / 60 (13.33%)
    9 / 59 (15.25%)
         occurrences all number
    8
    9

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Oct 2018
    Previous wording: Exclusion Criteria 11.Treatment with antibiotics (e.g., metronidazole or ciprofloxacin), New wording: Exclusion Criteria 11.Treatment with systemic broad-spectrum antibiotics (e.g., metronidazole or ciprofloxacin), Previous wording: Exclusion Criteria 15. Travelling to countries outside of Europe, USA, Australia or Canada within the last 12 weeks prior to baseline or during trial participation. New wording: Exclusion Criteria 15. Travelling to rural districts in countries outside of Europe, USA, Australia or Canada within the last 12 weeks prior to baseline or during trial participation. If patients travel outside of Europe, USA, Australia or Canada they must be tested negative in the standard stool tests (parasites, bacteria and virus) when they return, as at the screening visit. Previous wording: AE and Frequency New wording: Any patient suffering from an AE at trial end has to be followed up until resolution of the AE or up to a maximum of 4 weeks after the patient’s trial termination. After 4 weeks, the investigator should issue a final statement concerning the outcome of the AE. Previous wording: Fischer’s exact test will be used to test the hypothesis that there is no difference between the proportions in the TSO and placebo group. New wording: Chi-squared test (if events are more than 5) or Fischer’s exact test will be used to test the hypothesis that there is no difference between the proportions in the TSO and placebo group. New wording: Added a complete new Appendix 10 “Power of Attorney” and added a sentence in “Patient Data and Data Protection”. The patient signs a Power of Attorney to foreign health authorities to have access to all source data including the patient journal.
    21 Mar 2019
    Previous wording: Inclusion criteria 8. 5- Aminosalicyl acid (5-ASA) ≥ 8 weeks with a stable dose for at least 4 weeks both oral and rectal use. New wording: Inclusion criteria 8. No treatment or if treated with 5-Aminosalicyl acid (5-ASA): 5-ASA ≥ 8 weeks with a stable dose for at least 4 weeks both oral and rectal use. New wording: If the patient’s home address is more than 70 km from the site Hvidovre Hospital, the patient can receive transportation compensation. As a general rule, the compensation will cover the cheapest mode of transport. In the patient information folder (Appendix 8) the patient is informed that this compensation should be reported to the tax authority (SKAT). Hvidovre Hospital and the Region Hovedstaden’s system ”TUR” (Transport, Udlæg og Rejse Administration) will handle the compensation. Hvidovre Hospital, Gastro Unit will be compensated by the sponsor ParaTech A/S.
    09 Sep 2021
    On March 20 2020, ParaTech A/S informed the Danish Medicines Agency and IEC (VEK) about the COVID-19 Pandemic extraordinary initiatives in relation to the PROCTO study to reduce physical attendance of the patients at the clinical site, Hvidovre Hospital, and thus to minimize the risk of infection and to ensure continued and timely treatment during the PROCTO trial period. These COVID-19 pandemic extraordinary initiatives were described in the amendment. New wording added in the protocol page 50-52 (in abbreviated version): 1. Distribution of IMP doses from Hvidovre Hospital to the PROCTO patients (Temporary option to distribute directly to clinical trial subjects from sponsors (temporary exemption from §23 (2), of the GDP executive order because of COVID-19)) 2. Telephone / video consultations / study "visit". Possibility for visits 4-12 as telephone/video consultation and home pregnancy test before IMP administation. 3. Blood samples. Only if exacerbation of UC or if an AE occurs blood sampling should be performed at hospital. 4. Final sigmoidoscopy should be carried out at hospital as normal 5. Monitoring will continue according the COVID-19 restrictions. 6. Risk Assessment Report PROCTO and COVID-19 updated frequently 7. Advertisement for subject recruitment updated 8. The last 6 ongoing patients continue the extraordinary initiatives
    03 Nov 2021
    Adjustment of endpoints according to EMAs guideline "Guideline on the development of new medicinal products for the treatment of Ulcerative Colitis” New wording: Primary endpoint -To achieve clinical remission defined as full Mayo score ≤ 2 at 24 weeks (long-term efficacy) (ITT, PP) New wording: Secondary Endpoints - To achieve reduction of full Mayo score of 4 or more steps at 24 weeks (ITT, PP, complete steroid-free) - To achieve complete steroid free clinical remission defined as full Mayo score ≤ 2 at 24 weeks (long-term efficacy) (complete steroid-free) - To achieve endoscopic remission defined as mucosal appearance Mayo sub-score of 0 or 1 at 24 weeks (long-term efficacy) (ITT, PP, complete steroid-free) - To achieve symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 at 12 weeks (short-term efficacy) and at 24 weeks (long-term efficacy) (ITT, PP, complete steroid-free) - To reduce time to achieve remission defined as time to achieve a pMayo score ≤ 1 and time to achieve symptomatic remission defined as stool frequency Mayo sub-score of 0 or 1 and rectal bleeding Mayo sub-score of 0 (0-24 weeks) (ITT, PP, complete steroid-free) - To reduce time to achieve response defined as time to achieve reduction in pMayo score of 3 or more steps (0-24 weeks) (ITT, PP, complete steroid-free) - To decrease disease severity assessed by pMayo scores at visit 7 to 13 Explorative • Steroid use • Patients withdrawn due to worsening of disease • Mucosal healing • Calprotectin • Blood biomarkers • Immune profiling • Microbiome profiling • Patient-reported outcome

    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.
    None reported
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