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    Clinical Trial Results:
    A Phase 3 Randomized, Double-blind, Placebo controlled, Parallel group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects With Moderate to Severe Crohn’s Disease (CARMEN CD 306)

    Summary
    EudraCT number
    2017-000576-29
    Trial protocol
    IE   BE   HU   SK   ES   PT   EE   BG   GR  
    Global end of trial date
    18 Aug 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    03 May 2021
    First version publication date
    03 May 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    SHP647-306
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03566823
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Shire
    Sponsor organisation address
    300 Shire Way, Lexington, United States, MA 02421
    Public contact
    Study Director, Shire, ClinicalTransparency@takeda.com
    Scientific contact
    Study Director, Shire, ClinicalTransparency@takeda.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
    18 Aug 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Aug 2020
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the efficacy of ontamalimab in subjects with moderate to severe Crohn's disease (CD) in inducing clinical remission based on 2-item patient-reported outcome (PRO) (abdominal pain severity and very soft stool/liquid stool frequency) and inducing endoscopic response based on centrally read colonoscopy.
    Protection of trial subjects
    This study was conducted in accordance with International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 (1996), the principles of the Declaration of Helsinki, as well as other applicable local ethical and legal requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    17 Jul 2018
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    4 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 1
    Country: Number of subjects enrolled
    Colombia: 1
    Country: Number of subjects enrolled
    Japan: 1
    Country: Number of subjects enrolled
    Korea, Republic of: 1
    Country: Number of subjects enrolled
    Mexico: 2
    Country: Number of subjects enrolled
    Ukraine: 8
    Country: Number of subjects enrolled
    United States: 5
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Hungary: 3
    Country: Number of subjects enrolled
    Slovakia: 5
    Country: Number of subjects enrolled
    Spain: 5
    Worldwide total number of subjects
    34
    EEA total number of subjects
    15
    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)
    34
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study was conducted at 25 sites in the Unites States, Belgium, Bosnia and Herzegovina, Colombia, Hungary, Japan, Mexico, Slovakia, Republic of Korea, Spain and Ukraine between 17 July 2018 (first subject first visit) and 18 August 2020 (last subject last visit).

    Pre-assignment
    Screening details
    A total of 34 subjects were enrolled into the study, of which 27 subjects completed the study. Other secondary endpoints were not analyzed due to early discontinuation of the study for reasons unrelated to safety.

    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
    Subjects received ontamalimab matching-placebo, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period.
    Arm type
    Placebo

    Investigational medicinal product name
    Ontamalimab
    Investigational medicinal product code
    SHP647
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received placebo matched to ontamalimab SC injection, using a PFS.

    Arm title
    Ontamalimab 25 mg
    Arm description
    Subjects received ontamalimab 25 milligram (mg), injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period.
    Arm type
    Experimental

    Investigational medicinal product name
    Ontamalimab
    Investigational medicinal product code
    SHP647
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received 25 mg of ontamalimab SC injection, using a PFS.

    Arm title
    Ontamalimab 75 mg
    Arm description
    Subjects received ontamalimab 75 mg, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period.
    Arm type
    Experimental

    Investigational medicinal product name
    Ontamalimab
    Investigational medicinal product code
    SHP647
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received 75 mg of ontamalimab SC injection, using a PFS.

    Number of subjects in period 1
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Started
    6
    15
    13
    Completed
    4
    12
    11
    Not completed
    2
    3
    2
         Lack of efficacy
    -
    1
    -
         Adverse event, non-fatal
    1
    -
    2
         Consent withdrawn by subject
    1
    2
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects received ontamalimab matching-placebo, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period.

    Reporting group title
    Ontamalimab 25 mg
    Reporting group description
    Subjects received ontamalimab 25 milligram (mg), injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period.

    Reporting group title
    Ontamalimab 75 mg
    Reporting group description
    Subjects received ontamalimab 75 mg, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period.

    Reporting group values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg Total
    Number of subjects
    6 15 13 34
    Age categorical
    Units: subjects
        In utero
    0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0
        Newborns (0-27 days)
    0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0
        Children (2-11 years)
    0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0
        Adults (18-64 years)
    6 15 13 34
        From 65-84 years
    0 0 0 0
        85 years and over
    0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    42.4 ± 13.60 37.5 ± 10.20 39.1 ± 12.74 -
    Sex: Female, Male
    Units: subjects
        Female
    2 8 5 15
        Male
    4 7 8 19
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 1 0 1
        Asian
    0 2 0 2
        Native Hawaiian or Other Pacific Islander
    0 0 1 1
        Black or African American
    1 0 1 2
        White
    3 12 11 26
        More than one race
    0 0 0 0
        Unknown or Not Reported
    2 0 0 2
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    2 1 1 4
        Not Hispanic or Latino
    4 14 12 30
        Unknown or Not Reported
    0 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects received ontamalimab matching-placebo, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period.

    Reporting group title
    Ontamalimab 25 mg
    Reporting group description
    Subjects received ontamalimab 25 milligram (mg), injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period.

    Reporting group title
    Ontamalimab 75 mg
    Reporting group description
    Subjects received ontamalimab 75 mg, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period.

    Primary: Number of Subjects With Clinical Remission Based on 2-item Patient-reported Outcome (PRO) at Week 16

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    End point title
    Number of Subjects With Clinical Remission Based on 2-item Patient-reported Outcome (PRO) at Week 16 [1]
    End point description
    Clinical remission was defined by 2-item PRO subs-cores of average worst daily abdominal pain less than or equal to (<=) 3 (based on 11 point numerical rating scale [NRS] ranging from 0 [no pain] to 10 [worst imaginable pain]); and average daily stool frequency <=2 of type 6/7 (very soft stools/liquid stools) as per the Bristol Stool Form Scale (BSFS) over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid). Subjects with missing data at Week 16 or discontinuation before Week 16 were considered failures. Number of subjects with clinical remission were reported. The full analysis set (FAS) consisted of all subjects in the randomized set who had received at least 1 dose of IP.
    End point type
    Primary
    End point timeframe
    At Week 16
    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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    6
    15
    13
    Units: Subjects
    3
    5
    5
    No statistical analyses for this end point

    Primary: Number of Subjects With Endoscopic Response at Week 16

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    End point title
    Number of Subjects With Endoscopic Response at Week 16 [2]
    End point description
    Endoscopic response was defined as a decrease in Simple Endoscopic Score for Crohn’s disease (SES-CD) of at least 25 percent (%) from baseline. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Subjects with missing data at Week 16 or who discontinued before Week 16 were considered failures. Number of subjects with endoscopic response were reported. The FAS consisted of all subjects in the randomized set who had received at least 1 dose of IP.
    End point type
    Primary
    End point timeframe
    At Week 16
    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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    6
    15
    13
    Units: Subjects
    2
    10
    10
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinical Remission Based on Crohn's Disease Activity Index (CDAI) Score at Week 16

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    End point title
    Number of Subjects With Clinical Remission Based on Crohn's Disease Activity Index (CDAI) Score at Week 16
    End point description
    Clinical remission was defined as a CDAI score of <150. CDAI assesses CD based on clinical signs/symptoms such as number of liquid stools, intensity of abdominal pain, general well-being (subjective), and presence of complications, use of antidiarrheal, presence of abdominal mass, physical examination and hematocrit (objective). CDAI score is equal to sum of weighted scores for subjective and objective items which range from 0-149 points: asymptomatic remission, 150-220 points: mild to moderate active CD, 221-450 points: moderate to severe active CD, >451 points: severely active to fulminant disease. Higher score indicating more severity. Number of subjects with clinical remission as measured by CDAI were reported. The FAS consisted of all subjects in the randomized set who had received at least 1 dose of IP.
    End point type
    Secondary
    End point timeframe
    At Week 16
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    6
    15
    13
    Units: Subjects
    4
    8
    6
    No statistical analyses for this end point

    Secondary: Number of Subjects With Enhanced Endoscopic Response at Week 16

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    End point title
    Number of Subjects With Enhanced Endoscopic Response at Week 16
    End point description
    Enhanced endoscopic response was defined as a decrease in SES-CD by matching segments of at least 50% from baseline. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Subjects with missing data at Week 16 or who discontinued before Week 16 were considered non-responders. Number of subjects with enhanced endoscopic response were reported. The FAS consisted of all subjects in the randomized set who had received at least 1 dose of IP.
    End point type
    Secondary
    End point timeframe
    At Week 16
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    6
    15
    13
    Units: Subjects
    2
    5
    3
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinical Remission Based on 2-item PRO With 4-point Scale for Abdominal Pain at Week 16

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    End point title
    Number of Subjects With Clinical Remission Based on 2-item PRO With 4-point Scale for Abdominal Pain at Week 16
    End point description
    Clinical remission was defined by 2-item PRO subs-cores of average daily abdominal pain <=1 (based on the 4 point scale, with scores ranging from 0 [none] to 3 [severe]) over the 7 most recent days and average daily stool frequency <=3 of type 6/7 (very soft stools/liquid stools) as per the BSFS over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid). Subjects with missing data at Week 16 or who discontinued before Week 16 were considered failures. Number of subjects with enhanced endoscopic response were reported. The FAS consisted of all subjects in the randomized set who had received at least 1 dose of IP.
    End point type
    Secondary
    End point timeframe
    At Week 16
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    6
    15
    13
    Units: Subjects
    3
    6
    6
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinical Response Based on 2-item PRO With 2 Criteria at Week 16

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    End point title
    Number of Subjects With Clinical Response Based on 2-item PRO With 2 Criteria at Week 16
    End point description
    Clinical response was measured by 2-item PRO; defined as meeting at least 1 of the 2 criteria: 1)A decrease of >=30%and at least 2points from baseline in the average daily worst abdominal pain over the 7most recent days, with the average daily stool frequency of type 6/7(very soft/liquid stools)either a)not worsening from baseline and/or b)average daily stool frequency <=2 of type 6/7 as per the BSFS over the 7most recent days; 2)A decrease of >=30%from baseline in average daily stool frequency of type 6/7(very soft/liquid stools)as per the BSFS over the 7most recent days, with the average daily worst abdominal pain either a)not worsening from baseline and/or b)worst daily abdominal pain <=3(based on 11-point NRS)over the 7most recent days. Subjects with missing data or who discontinued at/before Week16 were considered failures. Number of subjects with clinical response were reported. The FAS consisted of all subjects in the randomized set who had received at least 1dose of IP.
    End point type
    Secondary
    End point timeframe
    At Week 16
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    6
    15
    13
    Units: Subjects
    5
    11
    8
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinical Remission Based on 2-Item PRO With Endoscopic Response at Week 16

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    End point title
    Number of Subjects With Clinical Remission Based on 2-Item PRO With Endoscopic Response at Week 16
    End point description
    Clinical remission was defined by 2-item PRO subs-cores of average worst daily abdominal pain <=3(based on 11point NRS ranging from 0[no pain] to 10[worst imaginable pain])and average daily stool frequency <=2 of type 6/7(very soft stools/liquid stools)as perBSFS ranging from type1(separate hard lumps-like stools)to type7(entirely liquid stools)over the 7most recent days. Endoscopic response was defined as a decrease in SES-CDof at least 25%from baseline. SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from0-3. Scale ranges from0-56 with a higher score indicating greater severity of disease. Subjects with missing data or who discontinued at/before Week16 were considered failures. Number of subjects with clinical remission with endoscopic response were reported. The FAS consisted of all subjects in the randomized set who had received at least 1dose of IP.
    End point type
    Secondary
    End point timeframe
    At Week 16
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    6
    15
    13
    Units: Subjects
    1
    4
    5
    No statistical analyses for this end point

    Secondary: Number of Subjects With Complete Endoscopic Healing at Week 16

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    End point title
    Number of Subjects With Complete Endoscopic Healing at Week 16
    End point description
    Clinical remission was defined by 2-item PRO subs-cores of average worst daily abdominal pain <=3(based on 11 point NRS ranging from 0 [no pain] to 10 [worst imaginable pain]) and average daily stool frequency <=2of type 6/7 (very soft stools/liquid stools)as per BSFS ranging from type1 (separate hard lumps-like stools) to type7 (entirely liquid stools) over the 7 most recent days. Endoscopic response was defined as a decrease in SES-CD of at least 25% from baseline. SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Subjects with missing data or who discontinued at/before Week16 were considered failures. Number of subjects with complete endoscopic healing were reported. The FAS consisted of all subjects in the randomized set who had received at least 1 dose of IP.
    End point type
    Secondary
    End point timeframe
    At Week 16
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    6
    15
    13
    Units: Subjects
    1
    3
    2
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinical Response as Measured by CDAI-100 at Week 16

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    End point title
    Number of Subjects With Clinical Response as Measured by CDAI-100 at Week 16
    End point description
    Clinical response is measured by at least a 100-point reduction in the CDAI from baseline (CDAI-100 response). CDAI assesses CD based on clinical signs/symptoms such as number of liquid stools, intensity of abdominal pain, general well-being (subjective), and presence of complications, use of antidiarrheal, presence of abdominal mass, physical examination and hematocrit (objective). CDAI score is equal to sum of weighted scores for subjective and objective items which range from 0-149 points: asymptomatic remission, 150-220 points: mild to moderate active CD, 221-450 points: moderate to severe active CD, >451 points: severely active to fulminant disease. Higher score indicating more severity. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
    End point type
    Secondary
    End point timeframe
    At Week 16
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    0 [3]
    0 [4]
    0 [5]
    Units: Subjects
    Notes
    [3] - Data collection and analysis for this endpoint was not performed due to study termination.
    [4] - Data collection and analysis for this endpoint was not performed due to study termination.
    [5] - Data collection and analysis for this endpoint was not performed due to study termination.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinical Response as Measured by CDAI-70 at Week 16

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    End point title
    Number of Subjects With Clinical Response as Measured by CDAI-70 at Week 16
    End point description
    Clinical response is measured by at least a 70-point reduction in the CDAI from baseline (CDAI-70 response). CDAI assesses CD based on clinical signs/symptoms such as number of liquid stools, intensity of abdominal pain, general well-being (subjective), and presence of complications, use of antidiarrheal, presence of abdominal mass, physical examination and hematocrit (objective). CDAI score is equal to sum of weighted scores for subjective and objective items which range from 0-149 points: asymptomatic remission, 150-220 points: mild to moderate active CD, 221-450 points: moderate to severe active CD, >451 points: severely active to fulminant disease. Higher score indicating more severity. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
    End point type
    Secondary
    End point timeframe
    At Week 16
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    0 [6]
    0 [7]
    0 [8]
    Units: Subjects
    Notes
    [6] - Data collection and analysis for this endpoint was not performed due to study termination.
    [7] - Data collection and analysis for this endpoint was not performed due to study termination.
    [8] - Data collection and analysis for this endpoint was not performed due to study termination.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinical Remission Over Time

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    End point title
    Number of Subjects With Clinical Remission Over Time
    End point description
    Clinical remission is defined by 2-item PRO subs-cores of average worst daily abdominal pain (based on 11 point NRS ranging from 0 [no pain] to 10 [worst imaginable pain]); and average daily stool frequency of type 6/7 (very soft stools/liquid stools) as per BSFS over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid). Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
    End point type
    Secondary
    End point timeframe
    At Week 16
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    0 [9]
    0 [10]
    0 [11]
    Units: Subjects
    Notes
    [9] - Data collection and analysis for this endpoint was not performed due to study termination.
    [10] - Data collection and analysis for this endpoint was not performed due to study termination.
    [11] - Data collection and analysis for this endpoint was not performed due to study termination.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Individual and Total Sign/Symptom Score Based on Subjects Daily Electronic Diary (e-diary) Entries

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    End point title
    Change From Baseline in Individual and Total Sign/Symptom Score Based on Subjects Daily Electronic Diary (e-diary) Entries
    End point description
    CD clinical signs and symptoms includes total stool frequency, rectal bleeding frequency, rectal urgency frequency, nausea severity, vomiting frequency, and rectal incontinence frequency. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 16
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    0 [12]
    0 [13]
    0 [14]
    Units: Subjects
    Notes
    [12] - Data collection and analysis for this endpoint was not performed due to study termination.
    [13] - Data collection and analysis for this endpoint was not performed due to study termination.
    [14] - Data collection and analysis for this endpoint was not performed due to study termination.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Endoscopic Healing at Week 16

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    End point title
    Number of Subjects With Endoscopic Healing at Week 16
    End point description
    Endoscopic healing is measured by SES-CD <=4 and at least 2-point reduction versus baseline and no sub-score >1 in any individual variable. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
    End point type
    Secondary
    End point timeframe
    At Week 16
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    0 [15]
    0 [16]
    0 [17]
    Units: Subjects
    Notes
    [15] - Data collection and analysis for this endpoint was not performed due to study termination.
    [16] - Data collection and analysis for this endpoint was not performed due to study termination.
    [17] - Data collection and analysis for this endpoint was not performed due to study termination.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total (Absolute) Score at Weeks 8, 12 and 16

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    End point title
    Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total (Absolute) Score at Weeks 8, 12 and 16
    End point description
    The IBDQ is a psychometrically validated PRO instrument for measuring the disease-specific health-related quality of life (HRQL) in subjects with IBD, including CD. The IBDQ consists of 32 items, which are grouped into 4 domains and scored as: bowel function (10 to 70), systemic symptoms (5 to 35), emotional status (12 to 84), and social function (5 to 35). The total IBDQ score ranges from 32 to 224. For the total score and each domain, a higher score indicates better HRQL. A score of at least 170 corresponds to clinical remission and an increase of at least 16 points is considered to indicate a clinically meaningful improvement. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 8, 12 and 16
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    0 [18]
    0 [19]
    0 [20]
    Units: Subjects
    Notes
    [18] - Data collection and analysis for this endpoint was not performed due to study termination.
    [19] - Data collection and analysis for this endpoint was not performed due to study termination.
    [20] - Data collection and analysis for this endpoint was not performed due to study termination.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Short Form-36 Health Survey (SF-36) Scores at Week 16

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    End point title
    Change From Baseline in Short Form-36 Health Survey (SF-36) Scores at Week 16
    End point description
    The SF-36, version 2 is a generic quality-of-life instrument that has been widely used to assess HRQL of subjects. The SF-36 consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role – physical, bodily pain, general health, vitality, social functioning, role – emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HRQL. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    0 [21]
    0 [22]
    0 [23]
    Units: Subjects
    Notes
    [21] - Data collection and analysis for this endpoint was not performed due to study termination.
    [22] - Data collection and analysis for this endpoint was not performed due to study termination.
    [23] - Data collection and analysis for this endpoint was not performed due to study termination.
    No statistical analyses for this end point

    Secondary: Number of Subjects Based on Incidence of All-cause Hospitalizations

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    End point title
    Number of Subjects Based on Incidence of All-cause Hospitalizations
    End point description
    Incidence of all cause hospitalizations was planned to be assessed. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 32
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    0 [24]
    0 [25]
    0 [26]
    Units: Subjects
    Notes
    [24] - Data collection and analysis for this endpoint was not performed due to study termination.
    [25] - Data collection and analysis for this endpoint was not performed due to study termination.
    [26] - Data collection and analysis for this endpoint was not performed due to study termination.
    No statistical analyses for this end point

    Secondary: Number of Subjects Based on Total Inpatient Days

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    End point title
    Number of Subjects Based on Total Inpatient Days
    End point description
    Total inpatient days were planed to be assessed. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 32
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    0 [27]
    0 [28]
    0 [29]
    Units: Subjects
    Notes
    [27] - Data collection and analysis for this endpoint was not performed due to study termination.
    [28] - Data collection and analysis for this endpoint was not performed due to study termination.
    [29] - Data collection and analysis for this endpoint was not performed due to study termination.
    No statistical analyses for this end point

    Secondary: Number of Subjects Based on Incidence of CD-related Surgeries and Other Surgical Procedures

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    End point title
    Number of Subjects Based on Incidence of CD-related Surgeries and Other Surgical Procedures
    End point description
    Incidence of CD-related surgeries and other surgical procedures were planned to be recorded. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 32
    End point values
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Number of subjects analysed
    0 [30]
    0 [31]
    0 [32]
    Units: Subjects
    Notes
    [30] - Data collection and analysis for this endpoint was not performed due to study termination.
    [31] - Data collection and analysis for this endpoint was not performed due to study termination.
    [32] - Data collection and analysis for this endpoint was not performed due to study termination.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From screening up to safety follow-up period (Week 32)
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects received ontamalimab matching-placebo, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period.

    Reporting group title
    Ontamalimab 25 mg
    Reporting group description
    Subjects received ontamalimab 25 mg, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period.

    Reporting group title
    Ontamalimab 75 mg
    Reporting group description
    Subjects received ontamalimab 75 mg, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period.

    Serious adverse events
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 15 (13.33%)
    2 / 13 (15.38%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    2 / 13 (15.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal stenosis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Placebo Ontamalimab 25 mg Ontamalimab 75 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 6 (100.00%)
    6 / 15 (40.00%)
    5 / 13 (38.46%)
    Injury, poisoning and procedural complications
    Chest injury
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Muscle strain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Road traffic accident
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Investigations
    Pain threshold decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Weight decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    White blood cell count increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 15 (13.33%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    Lymphadenopathy
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Memory impairment
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    General disorders and administration site conditions
    Injection site bruising
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 15 (13.33%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    2
    Anal fistula
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Constipation
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Crohn's disease
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    2
    0
    1
    Diarrhoea
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    1
    Dyspepsia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Large intestinal stenosis
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Nausea
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    2
    Reproductive system and breast disorders
    Menstruation irregular
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Pruritus generalised
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Urticaria
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Back pain
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Myalgia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Spondylitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Infections and infestations
    Fungal skin infection
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Gingival abscess
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Tonsillitis
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Ureteritis
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Aug 2018
    Protocol Amendment 1: Updated inclusion criteria to collect additional data for abdominal pain at study entry using the 0-3 CDAI severity scale. Updated exclusion criteria to exclude subjects with non steroidal anti-inflammatory drug-induced colitis, any history of positive tuberculosis (TB) and cirrhosis with or without decompensation; to clarify that subjects with positive hepatitis B core antibody (HBcAb), without hepatitis B virus (HBV) DNA and chronic hepatitis C virus (HCV), without HCV RNA may be eligible for the study. Added new new exclusion criterion to clarify that documentation of HIV status should be performed within 6 months of screening. Added text to clarify that concomitant antidiarrheal opiate drugs were permitted if taken at stable doses for the duration of the study, with dose reduction or discontinuation allowed only if required due to clinical improvement or adverse event. Added new section to provide appropriate guidance on subjects who have been enrolled with elevated liver function test or who have elevated liver function test(s) during the study.
    22 Nov 2019
    Protocol Amendment 2: Revised exclusion criterion to clarify that subjects with obstructive colonic stricture were to be excluded if it was clinically significant. Revised text to clarify the allowed doses of steroids. Added text to address FDA recommendation to evaluate the risk of hypersensitivity reactions in the Phase 3 studies and aid in the collection of relevant safety data. Updated the sample volume needed for the serum chemistry test and for the pharmacokinetic assessment.

    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 as the sponsor discontinued the ontamalimab clinical trial program in ulcerative colitis and CD for reasons unrelated to safety.
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