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    Clinical Trial Results:
    A Phase 2 Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Induction Therapy with 2 Doses of TD-1473 in Subjects with Moderately-to-Severely Active Crohn’s Disease

    Summary
    EudraCT number
    		 2018-001272-37
    Trial protocol
    		 FR   DE   PT   ES   HU   BG   AT   GB   GR   HR   RO  
    Global end of trial date
    30 Dec 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Jan 2023
    First version publication date
    16 Jan 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    0173
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03635112
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Theravance Biopharma Ireland Limited
    Sponsor organisation address
    Ten Earlsfort Terrace, Dublin, Ireland, D02 T380
    Public contact
    Medical Monitor, Theravance Biopharma, +1 855-633-8479, medinfo@theravance.com
    Scientific contact
    Medical Monitor, Theravance Biopharma, +1 855-633-8479, medinfo@theravance.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
    30 Dec 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Dec 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objectives of the study are as follows: • To assess the effect of TD-1473 compared to placebo in improving Crohn’s Disease Activity Index (CDAI) score at Week 12 in subjects with moderately-to-severely active CD • To assess the safety and tolerability of TD-1473
    Protection of trial subjects
    This trial was conducted in accordance with the ethical principles of Good Clinical Practice, according to the International Council for Harmonisation (ICH) Harmonised Tripartite Guideline.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    19 Jul 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 3
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    Australia: 5
    Country: Number of subjects enrolled
    South Africa: 4
    Country: Number of subjects enrolled
    Poland: 26
    Country: Number of subjects enrolled
    Russian Federation: 20
    Country: Number of subjects enrolled
    Ukraine: 20
    Country: Number of subjects enrolled
    Serbia: 9
    Country: Number of subjects enrolled
    Bulgaria: 8
    Country: Number of subjects enrolled
    Croatia: 4
    Country: Number of subjects enrolled
    Georgia: 2
    Country: Number of subjects enrolled
    Hungary: 2
    Country: Number of subjects enrolled
    United States: 28
    Country: Number of subjects enrolled
    France: 11
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Romania: 3
    Country: Number of subjects enrolled
    New Zealand: 2
    Worldwide total number of subjects
    159
    EEA total number of subjects
    67
    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)
    152
    From 65 to 84 years
    7
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 167 participants were randomized, of which 159 participants were eligible for analysis at sites in Australia, Asia/Pacific, Israel, Russia, the United States and South Africa between 19 November 2018 and 30 December 2021.

    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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants were randomized to receive once-daily oral administrations of placebo for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Received orally.

    Arm title
    		 TD-1473 80 mg
    Arm description
    		 Participants were randomized to receive once-daily oral administrations of TD-1473 80 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TD-1473
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Received orally.

    Arm title
    		 TD-1473 200 mg
    Arm description
    		 Participants were randomized to receive once-daily oral administrations of TD-1473 200 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 200 mg in the Active Treatment Extension period for up to 48 additional weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TD-1473
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Received orally.

    Number of subjects in period 1
    		Placebo TD-1473 80 mg TD-1473 200 mg
    Started
    38
    58
    63
    Completed Week 12 Visit
    33
    48
    49
    Completed
    12
    16
    13
    Not completed
    26
    42
    50
         Consent withdrawn by subject
    4
    9
    7
         Physician decision
    5
    7
    5
         Adverse event, non-fatal
    5
    9
    14
         Miscellaneous
    -
    -
    1
         Study Terminated by Sponsor
    11
    17
    21
         Lost to follow-up
    1
    -
    1
         Protocol deviation
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants were randomized to receive once-daily oral administrations of placebo for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.

    Reporting group title
    TD-1473 80 mg
    Reporting group description
    		 Participants were randomized to receive once-daily oral administrations of TD-1473 80 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.

    Reporting group title
    TD-1473 200 mg
    Reporting group description
    		 Participants were randomized to receive once-daily oral administrations of TD-1473 200 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 200 mg in the Active Treatment Extension period for up to 48 additional weeks.

    Reporting group values
    		 Placebo TD-1473 80 mg TD-1473 200 mg Total
    Number of subjects
    		 38 58 63 159
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 39.5 ± 14.85 37.1 ± 12.45 40.0 ± 13.64 -
    Gender categorical
    Units: Subjects
        Female
    		 18 28 31 77
        Male
    		 20 30 32 82
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 2 1 0 3
        Not Hispanic or Latino
    		 36 57 60 153
        Unknown
    		 0 0 2 2
        Not Reported
    		 0 0 1 1

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants were randomized to receive once-daily oral administrations of placebo for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.

    Reporting group title
    TD-1473 80 mg
    Reporting group description
    		 Participants were randomized to receive once-daily oral administrations of TD-1473 80 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.

    Reporting group title
    TD-1473 200 mg
    Reporting group description
    		 Participants were randomized to receive once-daily oral administrations of TD-1473 200 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 200 mg in the Active Treatment Extension period for up to 48 additional weeks.

    Primary: Change From Baseline in Crohn's Disease Activity Index (CDAI) Score

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    End point title
    		 Change From Baseline in Crohn's Disease Activity Index (CDAI) Score
    End point description
    The CDAI score was generated using regression coefficients for 8 predictors of disease activity: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight & hematocrit. The subscores of abdominal pain (0-3), general well-being (0-4), & number of very soft or liquid stools were then summed over the 7 days prior to each visit. The remaining predictors were also noted & weighted to create the total CDAI score. Benchmarks for disease activity were: <150, clinical remission; 150 to 219, mildly active disease; 220-450, moderately active disease; >450, very severe disease. Modified Intent-to-Treat Analysis Set: Comprised all randomized evaluable participants who received at least 1 dose of study drug and had at least one postbaseline CDAI score. Only participants with non-missing values at both baseline and postbaseline visit were included.
    End point type
    Primary
    End point timeframe
    Baseline to Week 12
    End point values
    		 Placebo TD-1473 80 mg TD-1473 200 mg
    Number of subjects analysed
    33
    47
    50
    Units: score on a scale
        least squares mean (standard error)
    -104.86 ± 15.496
    -105.62 ± 12.713
    -117.99 ± 12.423
    Statistical analysis title
    		 TD-1473 80 mg Versus Placebo
    Comparison groups
    Placebo v TD-1473 80 mg
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.97
    Method
    		 Mixed Model Repeated Measures Analysis
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -40.62
         upper limit
    		 39.11
    Statistical analysis title
    		 TD-1473 200 mg Versus Placebo
    Comparison groups
    Placebo v TD-1473 200 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.51
    Method
    		 Mixed Model Repeated Measures Analysis
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -13.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -52.46
         upper limit
    		 26.19

    Secondary: Number of Participants Who Demonstrated a Clinical Response as Measured by CDAI

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    End point title
    		 Number of Participants Who Demonstrated a Clinical Response as Measured by CDAI
    End point description
    The CDAI score was generated using regression coefficients for 8 predictors of disease activity: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight & hematocrit. The subscores of abdominal pain (0-3), general well-being (0-4), & number of very soft or liquid stools were then summed over the 7 days prior to each visit. The remaining predictors were also noted & weighted to create the total CDAI score. Benchmarks for disease activity were: <150, clinical remission; 150 to 219, mildly active disease; 220-450, moderately active disease; >450, very severe disease. Clinical response was defined as a reduction from baseline of ≥100 points or CDAI <150. The analysis set used was the Modified Intent-to-Treat Analysis Set.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo TD-1473 80 mg TD-1473 200 mg
    Number of subjects analysed
    35
    54
    56
    Units: participants
    19
    28
    34
    Statistical analysis title
    		 TD-1473 80 mg Versus Placebo
    Comparison groups
    Placebo v TD-1473 80 mg
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5102
    Method
    		 Cochran-Mantel-Haenszel Chi-square Test
    Parameter type
    		 Difference in Proportion
    Point estimate
    -0.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.277
         upper limit
    		 0.135
    Statistical analysis title
    		 TD-1473 200 mg Versus Placebo
    Comparison groups
    Placebo v TD-1473 200 mg
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8591
    Method
    		 Cochran-Mantel-Haenszel Chi-square Test
    Parameter type
    		 Difference in Proportion
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.181
         upper limit
    		 0.218

    Secondary: Number of Participants Who Demonstrated CDAI Clinical Remission

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    End point title
    		 Number of Participants Who Demonstrated CDAI Clinical Remission
    End point description
    The CDAI score was generated using regression coefficients for 8 predictors of disease activity: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight & hematocrit. The subscores of abdominal pain (0-3), general well-being (0-4), & number of very soft or liquid stools were then summed over the 7 days prior to each visit. The remaining predictors were also noted & weighted to create the total CDAI score. Benchmarks for disease activity were: <150, clinical remission; 150 to 219, mildly active disease; 220-450, moderately active disease; >450, very severe disease. CDAI clinical remission was defined as a CDAI score less than 150 at Week 12. The analysis set used was the Modified Intent-to-Treat Analysis Set.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo TD-1473 80 mg TD-1473 200 mg
    Number of subjects analysed
    35
    54
    56
    Units: participants
    13
    13
    22
    Statistical analysis title
    		 TD-1473 80 mg Versus Placebo
    Comparison groups
    Placebo v TD-1473 80 mg
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1805
    Method
    		 Cochran-Mantel-Haenszel Chi-square Test
    Parameter type
    		 Difference in Proportion
    Point estimate
    -0.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.322
         upper limit
    		 0.061
    Statistical analysis title
    		 TD-1473 200 mg Versus Placebo
    Comparison groups
    Placebo v TD-1473 200 mg
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9215
    Method
    		 Cochran-Mantel-Haenszel Chi-square Test
    Parameter type
    		 Difference in Proportion
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.204
         upper limit
    		 0.184

    Secondary: Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12

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    End point title
    		 Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12
    End point description
    The SES-CD incorporated 4 descriptors: the ulcer size, the proportion of surface covered by ulcer, the proportion of surface covered by other lesions, and the presence of stenosis. Each descriptor was graded from 0-3 and was scored in 5 segments (ileum, right colon, transverse colon, left colon, and rectum). The total score was calculated as the sum of all the items in each segment and ranged from 0 to 56, with higher scores indicating a worse outcome. The analysis set used was the Modified Intent-to-Treat Analysis Set including only participants who had non-missing values at both baseline and postbaseline visit.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12
    End point values
    		 Placebo TD-1473 80 mg TD-1473 200 mg
    Number of subjects analysed
    20
    35
    37
    Units: score on a scale
        least squares mean (standard error)
    -1.9 ± 1.27
    -0.2 ± 0.96
    -1.9 ± 0.95
    Statistical analysis title
    		 TD-1473 80 mg Versus Placebo
    Comparison groups
    Placebo v TD-1473 80 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.316
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 4.8
    Statistical analysis title
    		 TD-1473 200 mg Versus Placebo
    Comparison groups
    Placebo v TD-1473 200 mg
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.988
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.2
         upper limit
    		 3.2

    Secondary: Number of Participants With Endoscopic Response at Week 12

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    End point title
    		 Number of Participants With Endoscopic Response at Week 12
    End point description
    Endoscopic Response was defined as a reduction of SES-CD score or Endoscopic Remission (defined as SES-CD ≤ 2) at Week 12. The analysis set used was the Modified Intent-to-Treat Analysis Set.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo TD-1473 80 mg TD-1473 200 mg
    Number of subjects analysed
    31
    53
    54
    Units: participants
    6
    5
    15
    Statistical analysis title
    		 TD-1473 80 mg Versus Placebo
    Comparison groups
    Placebo v TD-1473 80 mg
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1828
    Method
    		 Cochran-Mantel-Haenszel Chi-square Test
    Parameter type
    		 Difference in Proportion
    Point estimate
    -0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.27
         upper limit
    		 0.059
    Statistical analysis title
    		 TD-1473 200 mg Versus Placebo
    Comparison groups
    Placebo v TD-1473 200 mg
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5785
    Method
    		 Cochran-Mantel-Haenszel Chi-square Test
    Parameter type
    		 Difference in Proportion
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.133
         upper limit
    		 0.244

    Secondary: Number of Participants With Stool Frequency and Abdominal Pain (SFAP) Clinical Remission

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    End point title
    		 Number of Participants With Stool Frequency and Abdominal Pain (SFAP) Clinical Remission
    End point description
    SFAP clinical remission was defined as an abdominal pain score ≤1 (on a scale of 0-3 with 0 representing ‘no pain’ and 3 representing ‘severe pain'), stool frequency ≤2.8, and both not worse than baseline at Week 12. The analysis set used was the Modified Intent-to-Treat Analysis Set.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo TD-1473 80 mg TD-1473 200 mg
    Number of subjects analysed
    35
    54
    56
    Units: participants
    6
    6
    10
    Statistical analysis title
    		 TD-1473 80 mg Versus Placebo
    Comparison groups
    Placebo v TD-1473 80 mg
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3776
    Method
    		 Cochran-Mantel-Haenszel Chi-square Test
    Parameter type
    		 Difference in Proportion
    Point estimate
    -0.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.225
         upper limit
    		 0.095
    Statistical analysis title
    		 TD-1473 200 mg Versus Placebo
    Comparison groups
    Placebo v TD-1473 200 mg
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6063
    Method
    		 Cochran-Mantel-Haenszel Chi-square Test
    Parameter type
    		 Difference in Proportion
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.189
         upper limit
    		 0.111

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Day 1 up to 28 days after the last dose (up to 64 weeks)
    Adverse event reporting additional description
    The safety analysis set comprised all participants who received at least 1 dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants were randomized to receive once-daily oral administrations of placebo for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.

    Reporting group title
    TD-1473 80 mg
    Reporting group description
    		 Participants were randomized to receive once-daily oral administrations of TD-1473 80 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 80 mg in the Active Treatment Extension period for up to 48 additional weeks.

    Reporting group title
    TD-1473 80mg Post-Placebo
    Reporting group description
    		 Participants who were treated with placebo in Induction Period and switched to TD-1473 80mg in Active Treatment Extension period.

    Reporting group title
    TD-1473 200 mg
    Reporting group description
    		 Participants were randomized to receive once-daily oral administrations of TD-1473 200 mg for 12 weeks during the Induction Period. Participants who completed the Induction Period received once-daily oral administrations of TD-1473 200 mg in the Active Treatment Extension period for up to 48 additional weeks.

    Serious adverse events
    		 Placebo TD-1473 80 mg TD-1473 80mg Post-Placebo TD-1473 200 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 38 (7.89%)
    9 / 58 (15.52%)
    3 / 33 (9.09%)
    10 / 63 (15.87%)
         number of deaths (all causes)
    1
    0
    0
    0
         number of deaths resulting from adverse events
    1
    0
    0
    0
    Investigations
    Transaminases increased
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 58 (0.00%)
    0 / 33 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Intentional overdose
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 58 (0.00%)
    0 / 33 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Vasculitis
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 58 (1.72%)
    0 / 33 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Granuloma
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 58 (0.00%)
    0 / 33 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 58 (0.00%)
    1 / 33 (3.03%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Crohn's Disease
         subjects affected / exposed
    0 / 38 (0.00%)
    6 / 58 (10.34%)
    1 / 33 (3.03%)
    8 / 63 (12.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 58 (1.72%)
    0 / 33 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intussusception
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 58 (0.00%)
    1 / 33 (3.03%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 58 (0.00%)
    0 / 33 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 58 (1.72%)
    0 / 33 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 58 (1.72%)
    0 / 33 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 58 (0.00%)
    0 / 33 (0.00%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 58 (0.00%)
    0 / 33 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo TD-1473 80 mg TD-1473 80mg Post-Placebo TD-1473 200 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 38 (28.95%)
    23 / 58 (39.66%)
    7 / 33 (21.21%)
    22 / 63 (34.92%)
    Investigations
    SARS-CoV-2 test positive
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 58 (1.72%)
    0 / 33 (0.00%)
    4 / 63 (6.35%)
         occurrences all number
    0
    1
    0
    5
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 38 (7.89%)
    3 / 58 (5.17%)
    1 / 33 (3.03%)
    5 / 63 (7.94%)
         occurrences all number
    3
    3
    3
    7
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 38 (0.00%)
    4 / 58 (6.90%)
    0 / 33 (0.00%)
    1 / 63 (1.59%)
         occurrences all number
    0
    4
    0
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 58 (1.72%)
    1 / 33 (3.03%)
    4 / 63 (6.35%)
         occurrences all number
    1
    1
    1
    5
    Crohn's disease
         subjects affected / exposed
    3 / 38 (7.89%)
    8 / 58 (13.79%)
    2 / 33 (6.06%)
    7 / 63 (11.11%)
         occurrences all number
    3
    8
    2
    9
    Diarrhoea
         subjects affected / exposed
    0 / 38 (0.00%)
    3 / 58 (5.17%)
    0 / 33 (0.00%)
    1 / 63 (1.59%)
         occurrences all number
    0
    3
    0
    1
    Nausea
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 58 (1.72%)
    2 / 33 (6.06%)
    4 / 63 (6.35%)
         occurrences all number
    1
    1
    2
    4
    Vomiting
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 58 (1.72%)
    2 / 33 (6.06%)
    1 / 63 (1.59%)
         occurrences all number
    1
    1
    2
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    2 / 38 (5.26%)
    4 / 58 (6.90%)
    0 / 33 (0.00%)
    1 / 63 (1.59%)
         occurrences all number
    2
    4
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 58 (1.72%)
    1 / 33 (3.03%)
    1 / 63 (1.59%)
         occurrences all number
    2
    1
    1
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 38 (0.00%)
    3 / 58 (5.17%)
    0 / 33 (0.00%)
    1 / 63 (1.59%)
         occurrences all number
    0
    4
    0
    2
    Back pain
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 58 (1.72%)
    0 / 33 (0.00%)
    3 / 63 (4.76%)
         occurrences all number
    2
    1
    0
    3
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 58 (0.00%)
    1 / 33 (3.03%)
    5 / 63 (7.94%)
         occurrences all number
    0
    0
    1
    6
    Urinary tract infection
         subjects affected / exposed
    1 / 38 (2.63%)
    4 / 58 (6.90%)
    0 / 33 (0.00%)
    1 / 63 (1.59%)
         occurrences all number
    1
    6
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Apr 2018
    Amendment 1 included the following changes: - Theravance Biopharma Ireland Limited telephone number was removed - Stratification factors were updated - Minor adjustment in the targeted proportion of biologics-naïve participants - Treatment regimen updated - Inclusion and exclusion criteria updated - Fecal lactoferrin added to the fecal testing - Statistical analysis section updated - Schedule of study procedures updated - Fistula Drainage Assessment was added for applicable participants - Risk and Benefits section updated - Treatment failure definition added - Rationale for study design updated - Rationale for dose assignment updated - Treatment compliance definition updated - Medical history data collection updated - Biopsy location information added - Participant diaries updated - Prohibited and permitted medications sections updated - Adverse event of special interest (AESI) definition updated - References and appendices updated.
    13 Jul 2018
    Amendment 2 included updates to the following sections: Cover Page and Protocol Synopsis; Background and Rationale; Risks and Benefits; Inclusion and Exclusion Criteria; Schedule of Study Procedures; Screening Stage 1; Fecal Sampling; Ileocolonoscopy and Biopsies; Prohibited Medications; Subject Discontinuation; AESI; serious adverse event (SAE) and AESI reporting timeline; Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or SAEs; Major Analysis Protocol Deviations; and Appendices.
    28 Jun 2019
    Amendment 3 included updates to the following sections: Protocol Synopsis; Background and Rationale; Clinical Experience; Selection of Dose and Duration of Treatment; Study Design Overview; Study Population; Overview; Procedures by Visit; Inclusion and Exclusion Criteria; Schedule of Study Procedures; Coexisting Medical Conditions or Past Medical History; Concomitant Medications; Statistical Methods; Sample Size and Power; Study Procedures; Objectives; Study Endpoints; Blinding; Treatment Assignment; Females of Childbearing Potential and Acceptable Birth Control; Screening Stage 2; Medication History; Vital Signs; Physical Examination; Viral Hepatitis and Human Immunodeficiency Virus Serology Panel; Tuberculosis (TB) Test; Ileocolonoscopy and Biopsies; Fecal Samples; Subject Daily Diary; Permitted Medications; Subject Discontinuation; Informed Consent; Confidentiality; Access to Data and Documents; SAE; Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or SAEs; and Appendices.
    09 Jun 2020
    Amendment 4 included updates to the following sections: Protocol Synopsis; Clinical Experience; Inclusion and Exclusion Criteria; Schedule of Study Procedures; TB Test; Permitted Medications; Subject Replacement; Pregnancy; AESI; Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or SAEs; Clinical Events Committee; Electrocardiogram Data; References; and Appendices.

    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.
    The study was terminated by the sponsor on 16 November 2021 after a planned review by the Independent Data Monitoring Committee.
    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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