Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Multiple Ascending Dose Study (Induction Therapy) and Long-term Extension Therapy of an Anti-OX40 Monoclonal Antibody (KHK4083) in Subjects with Moderately Active Ulcerative Colitis

    Summary
    EudraCT number
    		 2015-001555-69
    Trial protocol
    		 HU   CZ   PL  
    Global end of trial date
    04 Oct 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 Dec 2019
    First version publication date
    29 Dec 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    4083-002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02647866
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Kyowa Kirin Pharmaceutical Development, Inc.
    Sponsor organisation address
    212 Carnegie Center, Suite 400, Princeton, United States, 08540
    Public contact
    Kaoru Okada, Kyowa Hakko Kirin Co., Ltd., +81 3 5205-7219, kaoru.okada@kyowa-kirin.co.jp
    Scientific contact
    Kaoru Okada, Kyowa Hakko Kirin Co., Ltd., +81 3 5205-7219, kaoru.okada@kyowa-kirin.co.jp
    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
    06 Jun 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Sep 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Oct 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    • Induction Therapy - Part A: To determine the safety and tolerability of administration of multiple ascending doses of KHK4083 and to select the highest dose tolerated by subjects with moderately active ulcerative colitis (UC) to recommend for use in Part B; • Induction Therapy - Part B: To determine if the recommended dose of KHK4083 identified in Part A improves the mucosa in subjects with moderately active UC at Week 12 as measured by the modified Mayo endoscopy subscore (mMES).
    Protection of trial subjects
    This study was conducted in full accordance with the Declaration of Helsinki, the ICH consolidated guideline E6 - GCP, and any applicable national and local laws and regulations. The Investigators were responsible for performing the study in accordance with the protocol and ICH E6 GCP, for collecting, recording, and reporting the data accurately and properly. Agreement of the Investigator to conduct and administer this study in accordance with the protocol was documented in separate study agreements with the Sponsor and other forms as required by national authorities in the country where the study center was located.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Dec 2015
    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
    Poland: 25
    Country: Number of subjects enrolled
    Romania: 2
    Country: Number of subjects enrolled
    Czech Republic: 3
    Country: Number of subjects enrolled
    Hungary: 6
    Country: Number of subjects enrolled
    Russian Federation: 20
    Country: Number of subjects enrolled
    Serbia: 9
    Country: Number of subjects enrolled
    United States: 1
    Worldwide total number of subjects
    66
    EEA total number of subjects
    36
    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)
    60
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Investigative sites in the US, Poland, Czech Republic, Russia, Romania, Serbia, and Hungary recruited patients from January 2016 until June 2017.

    Pre-assignment
    Screening details
    		 A total of 109 patients were screened during the recruiting period. Male and female subjects ≥18 years of age with moderately active UC, defined as a total Mayo Clinic score of 4 to 9 & an mMES of at least 2 as determined by a central reader, and disease that extends ≥ 15 cm from the anal verge were eligible to participate in this study.

    Period 1
    Period 1 title
    Double-Blind Induction Therapy
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1
    Arm description
    		 1.0 mg/kg
    Arm type
    		 Experimental

    Investigational medicinal product name
    KHK4083
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received 1.0 mg/kg of investigational product by IV infusion over 60 minutes (± 10 minutes) every 2 weeks from Week 0 (Day 1) to Week 10.

    Arm title
    		 Cohort 2
    Arm description
    		 3.0 mg/kg
    Arm type
    		 Experimental

    Investigational medicinal product name
    KHK4083
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received 3.0 mg/kg of investigational product by IV infusion over 60 minutes (± 10 minutes) every 2 weeks from Week 0 (Day 1) to Week 10.

    Arm title
    		 Cohort 3
    Arm description
    		 10.0 mg/kg
    Arm type
    		 Experimental

    Investigational medicinal product name
    KHK4083
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received 10.0 mg/kg of investigational product by IV infusion over 60 minutes (± 10 minutes) every 2 weeks from Week 0 (Day 1) to Week 10.

    Arm title
    		 Cohort 4
    Arm description
    		 maximum tolerated dose (10.0 mg/kg)
    Arm type
    		 Experimental

    Investigational medicinal product name
    KHK4083
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received the maximum tolerated dose (10.0 mg/kg) of investigational product by IV infusion over 60 minutes (± 10 minutes) every 2 weeks from Week 0 (Day 1) to Week 10.

    Arm title
    		 Placebo
    Arm description
    		 Placebo arm
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects in this cohort received placebo by IV infusion over 60 minutes (± 10 minutes) every 2 weeks from Week 0 (Day 1) to Week 10.

    Number of subjects in period 1
    		Cohort 1 Cohort 2 Cohort 3 Cohort 4 Placebo
    Started
    9
    10
    9
    21
    17
    Completed
    7
    8
    4
    17
    15
    Not completed
    2
    2
    5
    4
    2
         Consent withdrawn by subject
    -
    1
    2
    3
    -
         Physician decision
    -
    -
    1
    -
    1
         Adverse event, non-fatal
    -
    -
    2
    1
    -
         Patient moved to another country
    1
    -
    -
    -
    -
         Lack of efficacy
    1
    1
    -
    -
    1
    Period 2
    Period 2 title
    Long Term Extension (LTE) Therapy
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Cohort 1 LTE
    Arm description
    		 1.0 mg/kg
    Arm type
    		 Experimental

    Investigational medicinal product name
    KHK4083
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received 1.0 mg/kg of investigational product by IV infusion over 60 minutes (± 10 minutes) every 4 weeks from Week 12 to Week 48.

    Arm title
    		 Cohort 2 LTE
    Arm description
    		 3.0 mg/kg
    Arm type
    		 Experimental

    Investigational medicinal product name
    KHK4083
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects in this cohort were to receive one 3.0 mg/kg IV infusion every 4 weeks from Week 12 to Week 48 followed by an End-of-LTE Therapy visit at Week 52, and then proceed to the LTE Therapy Follow-up Period (Week 56 through Week 64).

    Arm title
    		 Placebo LTE
    Arm description
    		 Placebo arm
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The LTE was only active for subjects who entered it prior to approval of Protocol Amendment 2. Subjects in this cohort were to receive one IV infusion of placebo every 4 weeks from Week 12 to Week 48 followed by an End-of-LTE Therapy visit at Week 52, and then proceed to the LTE Therapy Follow-up Period.

    Number of subjects in period 2
    		Cohort 1 LTE Cohort 2 LTE Placebo LTE
    Started
    3
    5
    1
    Completed
    1
    0
    0
    Not completed
    2
    5
    1
         Consent withdrawn by subject
    1
    -
    -
         Transferred from LTE to OLE
    -
    5
    1
         Lack of efficacy
    1
    -
    -
    Period 3
    Period 3 title
    Open Label Extension (OLE) Therapy
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Cohort 2 OLE
    Arm description
    		 3.0 mg/kg
    Arm type
    		 Experimental

    Investigational medicinal product name
    KHK4083
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Each subject eligible to enroll in OLE was to receive 10 treatments of open-label KHK4083 as maintenance therapy, one IV infusion of 3.0 mg/kg every 4 weeks from Week 12 to Week 48 followed by an End-of-OLE Therapy visit at Week 52, and then proceed to the OLE Therapy Follow-up Period (Week 56 through Week 64).

    Arm title
    		 Cohort 3 OLE
    Arm description
    		 10.0 mg/kg
    Arm type
    		 Experimental

    Investigational medicinal product name
    KHK4083
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Each subject eligible to enroll in OLE was to receive 10 treatments of open-label KHK4083 as maintenance therapy, one IV infusion of 10.0 mg/kg every 4 weeks from Week 12 to Week 48 followed by an End-of-OLE Therapy visit at Week 52, and then proceed to the OLE Therapy Follow-up Period (Week 56 through Week 64).

    Arm title
    		 Cohort 4 OLE
    Arm description
    		 maximum tolerated dose (10.0 mg/kg)
    Arm type
    		 Experimental

    Investigational medicinal product name
    KHK4083
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Each subject eligible to enroll in OLE was to receive 10 treatments of open-label KHK4083 as maintenance therapy, one IV infusion of 10.0 mg/kg every 4 weeks from Week 12 to Week 48 followed by an End-of-OLE Therapy visit at Week 52, and then proceed to the OLE Therapy Follow-up Period (Week 56 through Week 64).

    Arm title
    		 Placebo OLE
    Arm description
    		 Placebo subjects now receiving study drug as maintenance therapy
    Arm type
    		 Experimental

    Investigational medicinal product name
    KHK4083
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received either 1.0 mg/kg, 3.0 mg/kg, or 10.0 mg/kg of investigational product by IV infusion every 4 weeks from Week 12 to Week 48 as maintenance therapy, depending on which cohort they were enrolled in during Double-Blind Induction Therapy.

    Number of subjects in period 3
    		Cohort 2 OLE Cohort 3 OLE Cohort 4 OLE Placebo OLE
    Started
    3
    8
    24
    12
    Completed
    6
    5
    21
    9
    Not completed
    2
    3
    3
    5
         Adverse event, serious fatal
    1
    -
    -
    -
         Physician decision
    1
    -
    -
    1
         Consent withdrawn by subject
    -
    3
    1
    3
         Adverse event, non-fatal
    -
    -
    2
    1
    Joined
    5
    0
    0
    2
         Transferred from LTE to OLE
    5
    -
    -
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Double-Blind Induction Therapy
    Reporting group description
    		 -

    Reporting group values
    		 Double-Blind Induction Therapy Total
    Number of subjects
    		 66 66
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 60 60
        From 65-84 years
    		 6 6
        85 years and over
    		 0 0
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    		 40.8 (18 to 78) -
    Gender categorical
    Units: Subjects
        Female
    		 25 25
        Male
    		 41 41
    Subject analysis sets

    Subject analysis set title
    KHK4083 1.0 mg/kg SAS
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects receiving KHK4083 in Cohort 1

    Subject analysis set title
    KHK4083 3.0 mg/kg SAS
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects receiving KHK4083 in Cohort 2

    Subject analysis set title
    KHK4083 10.0 mg/kg SAS
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects receiving KHK4083 in Cohorts 3 and 4

    Subject analysis set title
    Placebo SAS
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects receiving placebo in all cohorts

    Subject analysis set title
    KHK4083 1.0 mg/kg FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects who received at least one full dose of investigational product and who had Baseline data and at least one post-treatment assessment of the primary efficacy variable.

    Subject analysis set title
    KHK4083 3.0 mg/kg FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    all subjects who received at least one full dose of investigational product and who had Baseline data and at least one post-treatment assessment of the primary efficacy variable.

    Subject analysis set title
    KHK4083 10.0 mg/kg FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    all subjects who received at least one full dose of investigational product and who had Baseline data and at least one post-treatment assessment of the primary efficacy variable.

    Subject analysis set title
    Placebo FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    all subjects who received at least one full dose of investigational product and who had Baseline data and at least one post-treatment assessment of the primary efficacy variable.

    Subject analysis sets values
    		 KHK4083 1.0 mg/kg SAS KHK4083 3.0 mg/kg SAS KHK4083 10.0 mg/kg SAS Placebo SAS KHK4083 1.0 mg/kg FAS KHK4083 3.0 mg/kg FAS KHK4083 10.0 mg/kg FAS Placebo FAS
    Number of subjects
    9
    10
    30
    17
    7
    8
    22
    15
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    7
    8
    28
    17
    4
    7
    21
    15
        From 65-84 years
    2
    2
    2
    0
    1
    1
    1
    0
        85 years and over
    0
    0
    0
    0
    0
    0
    0
    0
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    42.9 (18 to 67)
    46.1 (21 to 75)
    41.1 (18 to 78)
    33.8 (18 to 61)
    47.9 (18 to 67)
    44.8 (21 to 75)
    43.1 (23 to 70)
    34.2 (18 to 61)
    Gender categorical
    Units: Subjects
        Female
    4
    2
    11
    8
    3
    2
    7
    6
        Male
    5
    8
    19
    9
    4
    6
    15
    9

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Cohort 1
    Reporting group description
    		 1.0 mg/kg

    Reporting group title
    Cohort 2
    Reporting group description
    		 3.0 mg/kg

    Reporting group title
    Cohort 3
    Reporting group description
    		 10.0 mg/kg

    Reporting group title
    Cohort 4
    Reporting group description
    		 maximum tolerated dose (10.0 mg/kg)

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo arm
    Reporting group title
    Cohort 1 LTE
    Reporting group description
    		 1.0 mg/kg

    Reporting group title
    Cohort 2 LTE
    Reporting group description
    		 3.0 mg/kg

    Reporting group title
    Placebo LTE
    Reporting group description
    		 Placebo arm
    Reporting group title
    Cohort 2 OLE
    Reporting group description
    		 3.0 mg/kg

    Reporting group title
    Cohort 3 OLE
    Reporting group description
    		 10.0 mg/kg

    Reporting group title
    Cohort 4 OLE
    Reporting group description
    		 maximum tolerated dose (10.0 mg/kg)

    Reporting group title
    Placebo OLE
    Reporting group description
    		 Placebo subjects now receiving study drug as maintenance therapy

    Subject analysis set title
    KHK4083 1.0 mg/kg SAS
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects receiving KHK4083 in Cohort 1

    Subject analysis set title
    KHK4083 3.0 mg/kg SAS
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects receiving KHK4083 in Cohort 2

    Subject analysis set title
    KHK4083 10.0 mg/kg SAS
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects receiving KHK4083 in Cohorts 3 and 4

    Subject analysis set title
    Placebo SAS
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects receiving placebo in all cohorts

    Subject analysis set title
    KHK4083 1.0 mg/kg FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects who received at least one full dose of investigational product and who had Baseline data and at least one post-treatment assessment of the primary efficacy variable.

    Subject analysis set title
    KHK4083 3.0 mg/kg FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    all subjects who received at least one full dose of investigational product and who had Baseline data and at least one post-treatment assessment of the primary efficacy variable.

    Subject analysis set title
    KHK4083 10.0 mg/kg FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    all subjects who received at least one full dose of investigational product and who had Baseline data and at least one post-treatment assessment of the primary efficacy variable.

    Subject analysis set title
    Placebo FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    all subjects who received at least one full dose of investigational product and who had Baseline data and at least one post-treatment assessment of the primary efficacy variable.

    Primary: Proportion of subjects with treatment-related adverse events

    		 Close Top of page
    End point title
    		 Proportion of subjects with treatment-related adverse events [1]
    End point description
    A TEAE was an AE which started after the first dose of Investigational Product (KHK4083 or Placebo) but was within 16 weeks after the last dose. Overall, KHK4083 had a safety profile that was in line with expectations, the TEAEs were mostly mild or moderate by intensity and were manageable by the current standard of care therapies. The single case of death due to myocardial infarction in a subject with pre-existing coronary heart disease was considered as not study drug related by the Investigator.
    End point type
    Primary
    End point timeframe
    up to 52 weeks
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analysis was used for this primary end point.
    End point values
    		 KHK4083 1.0 mg/kg SAS KHK4083 3.0 mg/kg SAS KHK4083 10.0 mg/kg SAS Placebo SAS
    Number of subjects analysed
    9
    10
    30
    17
    Units: Subjects
        With Any TEAE
    5
    7
    21
    13
        With Any Drug-related TEAE
    3
    2
    6
    2
        With Any TEAE with an Outcome of Death
    0
    1
    0
    0
        With Any TEAE Leading to Discontinuation (DC)
    0
    1
    3
    1
        With Any Drug-related TEAE Leading to DC
    0
    0
    1
    0
    No statistical analyses for this end point

    Primary: Proportion of subjects with treatment-related serious adverse events

    		 Close Top of page
    End point title
    		 Proportion of subjects with treatment-related serious adverse events [2]
    End point description
    A TEAE was an AE which started after the first dose of Investigational Product (KHK4083 or Placebo) but was within 16 weeks after the last dose. Overall, KHK4083 had a safety profile that was in line with expectations, the TEAEs were mostly mild or moderate by intensity and were manageable by the current standard of care therapies. The single case of death due to myocardial infarction in a subject with pre-existing coronary heart disease was considered as not study drug related by the Investigator.
    End point type
    Primary
    End point timeframe
    up to 52 weeks
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analysis was used for this primary end point.
    End point values
    		 KHK4083 1.0 mg/kg SAS KHK4083 3.0 mg/kg SAS KHK4083 10.0 mg/kg SAS Placebo SAS
    Number of subjects analysed
    9
    10
    30
    17
    Units: Subjects
        With Any Serious TEAE
    1
    1
    4
    3
        With Any Drug-related Serious TEAE
    0
    0
    0
    0
        Who Died
    0
    1
    0
    0
    No statistical analyses for this end point

    Primary: Proportion of subjects who show improvement in the mucosa at Week 12

    		 Close Top of page
    End point title
    		 Proportion of subjects who show improvement in the mucosa at Week 12 [3]
    End point description
    Measured by the modified Mayo endoscopy sub-score (mMES)
    End point type
    Primary
    End point timeframe
    12 weeks
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis is provided in attached summary table.
    End point values
    		 KHK4083 1.0 mg/kg FAS KHK4083 3.0 mg/kg FAS KHK4083 10.0 mg/kg FAS Placebo FAS
    Number of subjects analysed
    7
    8
    22
    15
    Units: Subjects
        mMES Improvement
    2
    4
    9
    5
        Modified Baron Endoscopic Score Improvement
    3
    5
    8
    6
    Attachments
    		 Summary of Change from Baseline of UCEIS
    No statistical analyses for this end point

    Primary: Proportion of subjects who show improvement in the mucosa at Week 52

    		 Close Top of page
    End point title
    		 Proportion of subjects who show improvement in the mucosa at Week 52 [4]
    End point description
    Improvement in the Mucosa at Week 52 was observed in 14.3% (1 of 7 subjects) of the subjects receiving 1.0 mg/kg KHK4083; there were no subjects in the 3.0 mg/kg or 10.0 mg/kg KHK4083 or Placebo groups in the Double-Blind Therapy Period. During OLE Therapy Period, Improvement in the Mucosa at Week 52 was observed in 37.5% (3 of 8 subjects) and 42.9% (9 of 21 subjects) of the subjects receiving 3.0 mg/kg and 10.0 mg/kg KHK4083, respectively. There were no subjects in the 1.0 mg/kg KHK4083 group in the OLE Therapy Period.
    End point type
    Primary
    End point timeframe
    52 weeks
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analysis was used for this primary endpoint.
    End point values
    		 KHK4083 1.0 mg/kg FAS KHK4083 3.0 mg/kg FAS KHK4083 10.0 mg/kg FAS Placebo FAS
    Number of subjects analysed
    7
    8
    21
    14
    Units: Subjects
    1
    3
    9
    4
    No statistical analyses for this end point

    Secondary: Proportion of Subjects Who Achieve Mucosal Healing at Week 12

    		 Close Top of page
    End point title
    		 Proportion of Subjects Who Achieve Mucosal Healing at Week 12
    End point description
    End point type
    Secondary
    End point timeframe
    12 Weeks
    End point values
    		 KHK4083 1.0 mg/kg FAS KHK4083 3.0 mg/kg FAS KHK4083 10.0 mg/kg FAS Placebo FAS
    Number of subjects analysed
    7
    8
    22
    15
    Units: Subjects
    1
    3
    8
    4
    No statistical analyses for this end point

    Secondary: Proportion of Subjects Who Achieve Mucosal Healing at Week 52

    		 Close Top of page
    End point title
    		 Proportion of Subjects Who Achieve Mucosal Healing at Week 52
    End point description
    Mucosal healing is defined as modified Mayo endoscopy sub-score (mMES) of 0 or 1
    End point type
    Secondary
    End point timeframe
    52 Weeks
    End point values
    		 KHK4083 1.0 mg/kg FAS KHK4083 3.0 mg/kg FAS KHK4083 10.0 mg/kg FAS Placebo FAS
    Number of subjects analysed
    7
    8
    21
    14
    Units: Subjects
    1
    3
    7
    3
    No statistical analyses for this end point

    Secondary: Proportion of Subjects Who Achieve Clinical Improvement at Week 12

    		 Close Top of page
    End point title
    		 Proportion of Subjects Who Achieve Clinical Improvement at Week 12
    End point description
    Improvement will be based on a reduction in the total Mayo Clinic score (0 to 12).
    End point type
    Secondary
    End point timeframe
    12 Weeks
    End point values
    		 KHK4083 1.0 mg/kg FAS KHK4083 3.0 mg/kg FAS KHK4083 10.0 mg/kg FAS Placebo FAS
    Number of subjects analysed
    7
    8
    22
    15
    Units: Subjects
    2
    4
    9
    5
    No statistical analyses for this end point

    Secondary: Proportion of Subjects Who Achieve a Clinical Response at Week 12

    		 Close Top of page
    End point title
    		 Proportion of Subjects Who Achieve a Clinical Response at Week 12
    End point description
    Clinical Response indicates the change from Baseline in the Total Mayo Clinic score <= -3 and the percentage change from Baseline in the Total Mayo Clinic score <= -30% to Week 12, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of <= 1.
    End point type
    Secondary
    End point timeframe
    12 Weeks
    End point values
    		 KHK4083 1.0 mg/kg FAS KHK4083 3.0 mg/kg FAS KHK4083 10.0 mg/kg FAS Placebo FAS
    Number of subjects analysed
    7
    8
    22
    15
    Units: Subjects
    3
    8
    11
    9
    No statistical analyses for this end point

    Secondary: Proportion of Subjects Who Achieve a Clinical Response at Week 52

    		 Close Top of page
    End point title
    		 Proportion of Subjects Who Achieve a Clinical Response at Week 52
    End point description
    Clinical Response indicates the change from Baseline in the Total Mayo Clinic score <= -3 and the percentage change from Baseline in the Total Mayo Clinic score <= -30% to Week 12, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of <= 1.
    End point type
    Secondary
    End point timeframe
    52 Weeks
    End point values
    		 KHK4083 1.0 mg/kg FAS KHK4083 3.0 mg/kg FAS KHK4083 10.0 mg/kg FAS Placebo FAS
    Number of subjects analysed
    7
    8
    21
    14
    Units: Subjects
    2
    4
    14
    5
    No statistical analyses for this end point

    Secondary: Proportion of Subjects Who Achieve Clinical Remission at Week 12

    		 Close Top of page
    End point title
    		 Proportion of Subjects Who Achieve Clinical Remission at Week 12
    End point description
    Clinical remission is defined as a total Mayo Clinic score of ≤ 2 and no subscores > 1
    End point type
    Secondary
    End point timeframe
    12 Weeks
    End point values
    		 KHK4083 1.0 mg/kg FAS KHK4083 3.0 mg/kg FAS KHK4083 10.0 mg/kg FAS Placebo FAS
    Number of subjects analysed
    7
    8
    22
    15
    Units: Subjects
    1
    3
    10
    3
    No statistical analyses for this end point

    Secondary: Proportion of Subjects Who Achieve Clinical Remission at Week 52

    		 Close Top of page
    End point title
    		 Proportion of Subjects Who Achieve Clinical Remission at Week 52
    End point description
    Clinical Remission = A Total Mayo Clinic Score <= 2 and no subscores > 1 at Week 52.
    End point type
    Secondary
    End point timeframe
    52 Weeks
    End point values
    		 KHK4083 1.0 mg/kg FAS KHK4083 3.0 mg/kg FAS KHK4083 10.0 mg/kg FAS Placebo FAS
    Number of subjects analysed
    7
    8
    21
    14
    Units: Subjects
    1
    3
    6
    5
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Subjects were monitored for any untoward medical occurrences from the time of signed Informed Consent through 16 weeks post dose.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Cohort 1 1.0 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 2 3.0 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 3 10.0 mg/kg
    Reporting group description
    		 -

    Reporting group title
    Cohort 4 10.0 mg/kg
    Reporting group description
    		 -

    Reporting group title
    COMBINED
    Reporting group description
    		 -

    Reporting group title
    PLACEBO
    Reporting group description
    		 -

    Serious adverse events
    		 Cohort 1 1.0 mg/kg Cohort 2 3.0 mg/kg Cohort 3 10.0 mg/kg Cohort 4 10.0 mg/kg COMBINED PLACEBO
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    3 / 21 (14.29%)
    6 / 49 (12.24%)
    3 / 17 (17.65%)
         number of deaths (all causes)
    0
    1
    0
    0
    1
    0
         number of deaths resulting from adverse events
    0
    0
    Investigations
    Blood albumin decreased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Surgical and medical procedures
    Abscess drainage
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    3 / 49 (6.12%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 1
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatotoxicity
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Clostridium difficile infection
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 1 1.0 mg/kg Cohort 2 3.0 mg/kg Cohort 3 10.0 mg/kg Cohort 4 10.0 mg/kg COMBINED PLACEBO
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 9 (55.56%)
    7 / 10 (70.00%)
    7 / 9 (77.78%)
    13 / 21 (61.90%)
    32 / 49 (65.31%)
    13 / 17 (76.47%)
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Chest discomfort
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Chills
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    3 / 49 (6.12%)
    0 / 17 (0.00%)
         occurrences all number
    1
    1
    0
    1
    3
    0
    Pyrexia
         subjects affected / exposed
    3 / 9 (33.33%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    6 / 49 (12.24%)
    0 / 17 (0.00%)
         occurrences all number
    3
    1
    1
    1
    6
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Sneezing
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Amylase increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Aspartate aminotransferase abnormal
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Blood creatine phosphokinase abnormal
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    2 / 49 (4.08%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    1
    2
    3
    1
    Blood folate decreased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    C-reactive protein increased
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Lipase increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Scar
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Congenital, familial and genetic disorders
    Renal aplasia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Cardiac disorders
    Sinus bradycardia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    2 / 49 (4.08%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    1
    0
    2
    1
    Paraesthesia
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 9 (22.22%)
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    3 / 21 (14.29%)
    7 / 49 (14.29%)
    3 / 17 (17.65%)
         occurrences all number
    2
    2
    0
    3
    7
    4
    Lymphopenia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 21 (4.76%)
    2 / 49 (4.08%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    1
    1
    2
    1
    Thrombocytopenia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Abdominal pain
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    3 / 9 (33.33%)
    0 / 21 (0.00%)
    3 / 49 (6.12%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    3
    0
    3
    1
    Abdominal pain lower
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Abdominal tenderness
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Colitis ulcerative
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    2 / 21 (9.52%)
    5 / 49 (10.20%)
    5 / 17 (29.41%)
         occurrences all number
    1
    1
    1
    2
    5
    5
    Diarrhoea
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    0
    0
    2
    0
    Flatulence
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Haemorrhoids
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Mouth ulceration
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    2 / 49 (4.08%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    1
    0
    2
    0
    Mucous stools
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Nausea
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    Vomiting
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 9 (22.22%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    3 / 49 (6.12%)
    1 / 17 (5.88%)
         occurrences all number
    2
    1
    0
    1
    3
    1
    Joint swelling
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Muscular weakness
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Myalgia
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    1 / 49 (2.04%)
    1 / 17 (5.88%)
         occurrences all number
    1
    0
    0
    0
    1
    1
    Infections and infestations
    Influenza
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Oral candidiasis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Oral herpes
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Pharyngitis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 49 (2.04%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    1
    1
    1
    Sinusitis
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    2 / 49 (4.08%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    1
    2
    0
    Tonsillitis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 21 (4.76%)
    1 / 49 (2.04%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    1
    1
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 21 (0.00%)
    0 / 49 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Oct 2015
    Updates: • Section 5, OBJECTIVES; Section 10.1.1, Primary Endpoints, Efficacy; and Section 12.3.1, Primary Efficacy Analysis – to change the primary objective/variable from the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score to the FDA suggested modified Mayo endoscopy subscore (mMES) with an amended endoscopy finding scoring (i.e., mild friability excluded from a subscore of 1). • Section 5, OBJECTIVES; Section 10.2, Secondary Efficacy Endpoints; and Section 12.3.2, Secondary Efficacy Analyses – to change the secondary objective/variable from Mayo Clinic Endoscopy subscore to UCEIS. • Section 5, OBJECTIVES; Section 10.3, Exploratory Endpoints; and Section 12.3.3, Exploratory Efficacy Analysis – to add the exploratory objective/variable of a more stringent definition of remission; defined as an mMES of 0 or 1, a stool frequency subscore of 0 or 1, and a rectal bleeding subscore of 0. • Section 7.2, Inclusion Criteria 6)a) – to increase the minimal dose of budesonide from 6 mg/day to 9 mg/day in the definition of an unsuccessful prior treatment. • Section 7.2, Inclusion Criteria 6)c) – to specify the minimal doses and duration of anti-TNFα antagonists in the definition of an unsuccessful prior treatment. • Section 7.5.1, Subject Withdrawal – to further clarify when the Investigator(s) may withdraw a subject from the study. • Section 7.5.2, Study or Investigative Site Termination – to define unacceptable overall safety risks that may result in recommendation for termination of the study. • Section 7.5.3, Criteria for Subject Removal from the Study – to identify additional reasons that a subject may be removed from the study. • Section 8.5, Prior and Concurrent Therapy – to clarify that daily, chronic antidiarrheal medications should not be taken. • Section 8.6.1, Study Visit Outside of Planned Scheduled - Delay in Dosing - to describe the handling of IP administration when visits are not within the study visit window.
    04 Oct 2016
    The changes that were made to the protocol are listed in the following table, along with the rationale for each change:

    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
    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.

    European Medicines Agency © 1995-Thu May 02 07:24:24 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA