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    Clinical Trial Results:
    A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of PF-06687234 as Add-On Therapy to Infliximab in Active Ulcerative Colitis Subjects Who Are Not in Remission (Build UC)

    Summary
    EudraCT number
    		 2017-002108-28
    Trial protocol
    		 BE   DE   ES   IT  
    Global end of trial date
    07 Jan 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Nov 2021
    First version publication date
    19 Nov 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    B7581002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03269695
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 18007181021, ClinicalTrials.gov_Inquiries@pfizer.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
    07 Jan 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Jan 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Jan 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    This study was the first to assess PF 06487234 as add on therapy to infliximab, intravenous (IV) regimen in subjects with active ulcerative colitis (UC). The study was terminated after an interim analysis, due to efficacy being considered unlikely to meet the projected target.
    Protection of trial subjects
    This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial subjects.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 Dec 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    Australia: 9
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Israel: 1
    Country: Number of subjects enrolled
    Italy: 2
    Country: Number of subjects enrolled
    Korea, Republic of: 2
    Country: Number of subjects enrolled
    Saudi Arabia: 1
    Country: Number of subjects enrolled
    Serbia: 1
    Country: Number of subjects enrolled
    Turkey: 1
    Country: Number of subjects enrolled
    United States: 1
    Worldwide total number of subjects
    20
    EEA total number of subjects
    4
    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)
    17
    From 65 to 84 years
    3
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 46 subjects were screened, of whom 20 were randomized and treated (10 subjects each in the Placebo + Infliximab and PF-06687234 20 mg + Infliximab treatment groups). Fifteen subjects completed the treatment.

    Pre-assignment
    Screening details
    		 Subjects with active histologic UC (histologic) for >= 4 months, and on a stable dose 5 to 10 milligram/kilogram (mg/kg) of Remicade, or protocol specified infliximab biosimilars for a minimum of 14 weeks prior to study entry with no anticipation of need for change in infliximab treatment regimen throughout the study were enrolled.

    Period 1
    Period 1 title
    PF-06687234 Treatment Period (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 + Infliximab
    Arm description
    		 Placebo for PF‑06687234 was administered as subcutaneous injection on Day 1, Week 1 (Day 8), Week 2 (Day 15), Week 3 (Day 22), Week 4 (Day 29), Week 5 (Day 36), Week 6 (Day 43), Week 7 (Day 50), Week 8 (Day 57), Week 9 (Day 64), Week 10 (Day 71) and Week 11 (Day 78) for a total 12 doses. Remicade or protocol specified infliximab biosimilar was administered as an IV infusion on Day 1, Week 8 and Week 16 for a total of 3 doses for subjects on infliximab every 8 weeks, and Day 1, Week 6, Week 12 and Week 18 for subjects on infliximab every 6 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo for PF-06687234
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    PF-06687234 0 mg/vial

    Investigational medicinal product name
    Infliximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Infliximab 100 mg/vial

    Arm title
    		 PF-06687234 20 mg + Infliximab
    Arm description
    		 PF-06687234 was administered as a 20 mg subcutaneous injection on Day 1, Week 1 (Day 8), Week 2 (Day 15), Week 3 (Day 22), Week 4 (Day 29), Week 5 (Day 36), Week 6 (Day 43), Week 7 (Day 50), Week 8 (Day 57), Week 9 (Day 64), Week 10 (Day 71) and Week 11 (Day 78) for a total 12 doses. Remicade or protocol specified infliximab biosimilar was administered as an IV infusion on Day 1, Week 8 and Week 16 for a total of 3 doses for subjects on infliximab every 8 weeks, and Day 1, Week 6, Week 12 and Week 18 for subjects on infliximab every 6 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Infliximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Infliximab 100 mg/vial

    Investigational medicinal product name
    PF-06687234
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    PF-06687234 20 mg/vial

    Number of subjects in period 1
    		Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Started
    10
    10
    Completed
    8
    7
    Not completed
    2
    3
         Consent withdrawn by subject
    -
    1
         Adverse event, non-fatal
    2
    1
         Lack of efficacy
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo + Infliximab
    Reporting group description
    		 Placebo for PF‑06687234 was administered as subcutaneous injection on Day 1, Week 1 (Day 8), Week 2 (Day 15), Week 3 (Day 22), Week 4 (Day 29), Week 5 (Day 36), Week 6 (Day 43), Week 7 (Day 50), Week 8 (Day 57), Week 9 (Day 64), Week 10 (Day 71) and Week 11 (Day 78) for a total 12 doses. Remicade or protocol specified infliximab biosimilar was administered as an IV infusion on Day 1, Week 8 and Week 16 for a total of 3 doses for subjects on infliximab every 8 weeks, and Day 1, Week 6, Week 12 and Week 18 for subjects on infliximab every 6 weeks.

    Reporting group title
    PF-06687234 20 mg + Infliximab
    Reporting group description
    		 PF-06687234 was administered as a 20 mg subcutaneous injection on Day 1, Week 1 (Day 8), Week 2 (Day 15), Week 3 (Day 22), Week 4 (Day 29), Week 5 (Day 36), Week 6 (Day 43), Week 7 (Day 50), Week 8 (Day 57), Week 9 (Day 64), Week 10 (Day 71) and Week 11 (Day 78) for a total 12 doses. Remicade or protocol specified infliximab biosimilar was administered as an IV infusion on Day 1, Week 8 and Week 16 for a total of 3 doses for subjects on infliximab every 8 weeks, and Day 1, Week 6, Week 12 and Week 18 for subjects on infliximab every 6 weeks.

    Reporting group values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab Total
    Number of subjects
    		 10 10 20
    Age Categorical
    Units: Subjects
        18-44 Years
    		 5 6 11
        45-64 Years
    		 2 4 6
        ≥ 65 Years
    		 3 0 3
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 44.6 ( 21.11 ) 44.5 ( 12.44 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 3 4 7
        Male
    		 7 6 13
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 8 8 16
        Asian
    		 2 2 4
    Race/Ethnicity, Customized
    Units: Subjects
        Not Hispanic or Latino
    		 10 10 20
    Age Continuous
    Units: Years
        median (full range (min-max))
    		 44.5 (20 to 73) 43.5 (20 to 64) -

    End points

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    End points reporting groups
    Reporting group title
    Placebo + Infliximab
    Reporting group description
    		 Placebo for PF‑06687234 was administered as subcutaneous injection on Day 1, Week 1 (Day 8), Week 2 (Day 15), Week 3 (Day 22), Week 4 (Day 29), Week 5 (Day 36), Week 6 (Day 43), Week 7 (Day 50), Week 8 (Day 57), Week 9 (Day 64), Week 10 (Day 71) and Week 11 (Day 78) for a total 12 doses. Remicade or protocol specified infliximab biosimilar was administered as an IV infusion on Day 1, Week 8 and Week 16 for a total of 3 doses for subjects on infliximab every 8 weeks, and Day 1, Week 6, Week 12 and Week 18 for subjects on infliximab every 6 weeks.

    Reporting group title
    PF-06687234 20 mg + Infliximab
    Reporting group description
    		 PF-06687234 was administered as a 20 mg subcutaneous injection on Day 1, Week 1 (Day 8), Week 2 (Day 15), Week 3 (Day 22), Week 4 (Day 29), Week 5 (Day 36), Week 6 (Day 43), Week 7 (Day 50), Week 8 (Day 57), Week 9 (Day 64), Week 10 (Day 71) and Week 11 (Day 78) for a total 12 doses. Remicade or protocol specified infliximab biosimilar was administered as an IV infusion on Day 1, Week 8 and Week 16 for a total of 3 doses for subjects on infliximab every 8 weeks, and Day 1, Week 6, Week 12 and Week 18 for subjects on infliximab every 6 weeks.

    Primary: Percentage of Subjects in Modified Clinical Remission at Week 12 (Traditional Mayo Endoscopic Subscore <=1, Observed Cases)

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    End point title
    		 Percentage of Subjects in Modified Clinical Remission at Week 12 (Traditional Mayo Endoscopic Subscore <=1, Observed Cases)
    End point description
    The Mayo score consists of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician’s global assessment [PGA]), each graded 0 to 3 with the higher score indicating more severe disease activity. Modified clinical remission is defined as a modified total Mayo Score (total Mayo score excluding the PGA subscore) <=2, no individual subscore >1, traditional endoscopic subscore <=1 (where mild friability was scored as of 1; moderate or severe friability was scored as 2) and rectal bleeding subscore = 0. All subjects who had at least one dose of the randomized treatment were included in the analysis population. Subjects with missing values were handled by observed case approach (the missing data were used as is). The number of subjects with observed data were 8 for the Placebo + Infliximab arm and 7 for PF-06687234 20 mg + Infliximab arm. The percentage of subjects achieving modified clinical remission was calculated based on the number of subjects with observed data.
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    8
    7
    Units: Percentage of subjects (%)
        number (confidence interval 95%)
    12.5 (0.6 to 50.0)
    14.3 (0.7 to 55.4)
    Statistical analysis title
    		 Treatment Difference Between 2 Arms
    Comparison groups
    Placebo + Infliximab v PF-06687234 20 mg + Infliximab
    Number of subjects included in analysis
    15
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 1
    Method
    		 Chan and Zhang (1999)
    Parameter type
    		 Treatment difference
    Point estimate
    1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -41
         upper limit
    		 47.2

    Primary: Percentage of Subjects in Modified Clinical Remission at Week 12 (Traditional Mayo Endoscopic Subscore <=1, Treatment Failure Approach)

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    End point title
    		 Percentage of Subjects in Modified Clinical Remission at Week 12 (Traditional Mayo Endoscopic Subscore <=1, Treatment Failure Approach)
    End point description
    The Mayo score consists of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician’s global assessment [PGA]), each graded 0 to 3 with the higher score indicating more severe disease activity. Modified clinical remission is defined as a modified total Mayo Score (total Mayo score excluding the PGA subscore) <=2, no individual subscore > 1, traditional endoscopic subscore <=1 (where mild friability was scored as of 1; moderate or severe friability was scored as 2) and rectal bleeding subscore = 0. All subjects who had received at least one dose of the randomized treatment were included in the analysis population. Subjects with missing values were handled by treatment failure approach (subjects who had missing value for any reasons were considered as treatment failures).
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    10
    10
    Units: Percentage of subjects (%)
        number (confidence interval 95%)
    10 (0.5 to 44.4)
    10 (0.5 to 44.4)
    Statistical analysis title
    		 Treatment Difference Between 2 Arms
    Comparison groups
    Placebo + Infliximab v PF-06687234 20 mg + Infliximab
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 1
    Method
    		 Chan and Zhang (1999)
    Parameter type
    		 Treatment difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -37
         upper limit
    		 37

    Primary: Percentage of Subjects in Modified Clinical Remission at Week 12 (Modified Mayo Endoscopy Subscore = 0 or 1, Observed Cases)

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    End point title
    		 Percentage of Subjects in Modified Clinical Remission at Week 12 (Modified Mayo Endoscopy Subscore = 0 or 1, Observed Cases)
    End point description
    The Mayo score consists of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician’s global assessment), each graded 0 to 3 with the higher score indicating more severe disease activity. Modified clinical remission is defined as a modified total Mayo Score (total Mayo score excluding the PGA subscore) with modified endoscopic subscore = 0 or 1 (where any friability was scored as a mayo endoscopic subscore of 2), stool frequency subscore = 0 or 1, and rectal bleeding subscore = 0. All subjects who had received at least one dose of the randomized treatment were included in the analysis population. Subjects with missing values were handled by observed case approach (the missing data were used as is). The number of subjects with observed data were 8 for the Placebo + Infliximab arm and 7 for PF-06687234 20mg + Infliximab arm. The percentage of subjects achieving modified clinical remission was calculated based on the number of subjects with observed data.
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    8
    7
    Units: Percentage of subjects (%)
        number (confidence interval 95%)
    0 (0.0 to 34.9)
    14.3 (0.7 to 55.4)
    Statistical analysis title
    		 Treatment Difference Between 2 Arms
    Comparison groups
    Placebo + Infliximab v PF-06687234 20 mg + Infliximab
    Number of subjects included in analysis
    15
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.47
    Method
    		 Chan and Zhang (1999)
    Parameter type
    		 Treatment difference
    Point estimate
    14.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.8
         upper limit
    		 57.9

    Primary: Percentage of Subjects in Modified Clinical Remission at Week 12 (Modified Mayo Endoscopy Subscore = 0 or 1, Treatment Failure Approach)

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    End point title
    		 Percentage of Subjects in Modified Clinical Remission at Week 12 (Modified Mayo Endoscopy Subscore = 0 or 1, Treatment Failure Approach)
    End point description
    The Mayo score consists of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician’s global assessment [PGA]), each graded 0 to 3 with the higher score indicating more severe disease activity. Modified clinical remission is defined as a modified total Mayo Score (total Mayo score excluding the PGA subscore) with modified endoscopic subscore = 0 or 1 (where any friability was scored as a mayo endoscopic subscore of 2), stool frequency subscore = 0 or 1, and rectal bleeding subscore = 0. All subjects who had received at least one dose of the randomized treatment were included in the analysis population. Subjects with missing values were handled by treatment failure approach (subjects who had missing value for any reasons were considered as treatment failures).
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    10
    10
    Units: Percentage of subjects (%)
        number (confidence interval 95%)
    0 (0.0 to 26.7)
    10 (0.5 to 44.4)
    Statistical analysis title
    		 Treatment Difference Between 2 Arms
    Comparison groups
    Placebo + Infliximab v PF-06687234 20 mg + Infliximab
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5221
    Method
    		 Chan and Zhang (1999)
    Parameter type
    		 Treatment difference
    Point estimate
    10
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.7
         upper limit
    		 45.6

    Primary: Number of Subjects with Treatment-Emergent Adverse Events (AEs; All Causalities)

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    End point title
    		 Number of Subjects with Treatment-Emergent Adverse Events (AEs; All Causalities) [1]
    End point description
    Treatment-emergent AEs are those with initial onset or that worsen in severity after the first dose of the study medication. An serious adverse event (SAE) is any untoward medical occurrence at any dose that: results in death; is life threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect; or that is considered to be an important medical event that may jeopardize the subjects or may require intervention to prevent one of the other AE outcomes. Severe AEs were defined as AEs that interfered significantly with subjects’s usual function. Both SAEs and severe AEs were according to the investigator's assessment. All subjects who had received at least one dose of the randomized treatment were included in the analysis population.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1) through and including a minimum of 28 calendar days after the last administration of the investigational products (22 weeks in total)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were planned for safety endpoints.
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    10
    10
    Units: Subjects
        Subjects with AEs
    8
    9
        Subjects with SAEs
    1
    0
        Subjects with severe AEs
    2
    0
        Subjects discontinued from study due to AEs
    0
    0
        IP discontinued due to AEs, subjects continued
    2
    1
        Subjects with temporary discontinuation due to AEs
    1
    1
    No statistical analyses for this end point

    Primary: Number of Subjects with Treatment-Emergent AEs (Treatment Related)

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    End point title
    		 Number of Subjects with Treatment-Emergent AEs (Treatment Related) [2]
    End point description
    Treatment-emergent AEs are those with initial onset or that worsen in severity after the first dose of the study medication. An SAE is any untoward medical occurrence at any dose that: results in death; is life threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect; or that is considered to be an important medical event that may jeopardize the subjects or may require intervention to prevent one of the other AE outcomes. Severe AEs were defined as AEs that interfered significantly with subjects’s usual function. Treatment-related AEs, SAEs and severe AEs were according to the investigator's assessment. All subjects who had received at least one dose of the randomized treatment were included in the analysis population.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1) through and including a minimum of 28 calendar days after the last administration of the investigational products (22 weeks in total)
    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: No statistical analysis were planned for safety endpoints.
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    10
    10
    Units: Subjects
        Subjects with AEs
    1
    7
        Subjects with SAEs
    0
    0
        Subjects with severe AEs
    0
    0
        Subjects discontinued from study due to AEs
    0
    0
        IP discontinued due to AEs, subjects continued
    1
    0
        Subjects with temporary discontinuation due to AEs
    0
    0
    No statistical analyses for this end point

    Primary: Number of Subjects with Laboratory Test Abnormalities Without Regard to Baseline Abnormality

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    End point title
    		 Number of Subjects with Laboratory Test Abnormalities Without Regard to Baseline Abnormality [3]
    End point description
    The laboratory tests as defined in the protocol, including hematology, chemistry, urinalysis and other, were performed. Baseline was defined as the last measurement prior to first dosing (Day 1). All subjects with at least one observation of the given laboratory test while on study treatment or during lag time were included in the analysis population. LLN=lower limit of normal; ULN=upper limit of normal; LPF=low-power field; n=number of subjects with a laboratory abnormality meeting specified criteria while on study treatment or during lag time.
    End point type
    Primary
    End point timeframe
    From baseline through Week 16
    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: No statistical analysis were planned for safety endpoints.
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    10
    10
    Units: Subjects
        Hemoglobin (g/dL) < 0.8 x LLN
    0
    2
        Hematocrit (%) < 0.8 x LLN
    0
    2
        Erythrocytes (10^6/mm^3) < 0.8 x LLN
    0
    2
        Reticulocytes (10^3/mm^3) > 1.5 x ULN
    0
    1
        Reticulocytes/Erythrocytes (%) > 1.5 x ULN
    0
    1
        Leukocytes (10^3/mm^3) > 1.5 x ULN
    0
    1
        Lymphocytes (10^3/mm^3) < 0.8 x LLN
    2
    2
        Lymphocytes/Leukocytes (%) < 0.8 x LLN
    1
    4
        Neutrophils (10^3/mm^3) < 0.8 x LLN
    1
    0
        Neutrophils (10^3/mm^3) > 1.2 x ULN
    0
    2
        Neutrophils/Leukocytes (%) < 0.8 x LLN
    0
    1
        Neutrophils/Leukocytes (%) > 1.2 x ULN
    0
    2
        Basophils/Leukocytes (%) > 1.2 x ULN
    1
    0
        Eosinophils (10^3/mm^3) > 1.2 x ULN
    0
    1
        Eosinophils/Leukocytes (%) > 1.2 x ULN
    1
    0
        Monocytes/Leukocytes (%) > 1.2 x ULN
    2
    2
        Protein (g/dL) < 0.8 x LLN
    0
    1
        Albumin (g/dL) < 0.8 x LLN
    1
    1
        Creatinine (mg/dL) > 1.3 x ULN
    0
    1
        Glucose (mg/dL) > 1.5 x ULN
    0
    1
        Ketones (Scalar) >=1
    1
    1
        Urine Protein (mg/dL) >=1
    1
    1
        Urine Hemoglobin (Scalar) >=1
    3
    3
        Leukocyte Esterase (Scalar) >=1
    4
    3
        Hyaline Casts (/LPF) > 1 (n=2, 2)
    0
    2
    No statistical analyses for this end point

    Primary: Number of Subjects With Categorical Vital Signs

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    End point title
    		 Number of Subjects With Categorical Vital Signs [4]
    End point description
    Single sitting blood pressure (BP), pulse rate, and temperature were measured. At Day 1 and Week 1, BP and pulse were collected approximately 30 minutes prior to dosing, approximately 30 minutes post dosing and approximately 1 hour post dosing. For subjects with no safety issues (eg, severe injection site reactions, severe elevations BP and/or pulse), BP and pulse were collected approximately 30 minutes prior to dosing and approximately 30 minutes post dosing from Weeks 2-16. Vital signs were analyzed as per pre-specified categories. All subjects who had received at least one dose of the randomized treatment were included in the analysis population.
    End point type
    Primary
    End point timeframe
    From baseline through Week 16
    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: No statistical analysis were planned for safety endpoints.
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    10
    10
    Units: Subjects
        Sitting systolic blood pressure (SBP) < 90 mmHg
    0
    0
        Increase in Sitting SBP >=30 mmHg
    2
    0
        Decrease in Sitting SBP >=30 mmHg
    0
    0
        Sitting diastolic blood pressure (DBP) < 50 mmHg
    0
    0
        Increase in Sitting DBP >=20 mmHg
    2
    2
        Decrease in Sitting DBP >=20 mmHg
    3
    2
        Sitting Pulse Rate < 40 beats/minute
    0
    0
        Sitting Pulse Rate > 120 beats/minute
    0
    0
    No statistical analyses for this end point

    Primary: Number of Subjects With Categorical Electrocardiogram (ECG) data

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    End point title
    		 Number of Subjects With Categorical Electrocardiogram (ECG) data [5]
    End point description
    Twelve (12) lead ECGs were collected. All scheduled ECGs were performed after the subjects had rested quietly for at least 10 minutes in a supine position. When the timing of these measurements coincided with a blood collection, the ECG was obtained prior to the nominal time of the blood collection, blood pressure, and pulse rate. ECG data were analyzed as per pre-specified categories. All subjects who had received at least one dose of the randomized treatment were included in the analysis population. PR=pulse rate; QTc=QT interval corrected for heart rate; QTcF=QTc corrected using Fridericia’s formula.
    End point type
    Primary
    End point timeframe
    From baseline through Week 16
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were planned for safety endpoints.
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    10
    10
    Units: Subjects
        PR Interval >=300 millisecond (msec)
    0
    0
        Change in PR Interval (%) >=25/50%
    0
    0
        QRS Complex >=140 msec
    0
    0
        Change in QRS Complex (%) >=50%
    0
    0
        QT Interval >=500 msec
    0
    0
        450 msec <= QTcF < 480 msec
    0
    0
        480 msec <= QTcF < 500 msec
    0
    0
        QTcF >=500 msec
    0
    0
        30 msec <= change in QTcF < 60 msec
    0
    1
        Change in QTcF >= 60 msec
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Endoscopic Improvement at Week 12 (Observed Cases)

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    End point title
    		 Percentage of Subjects With Endoscopic Improvement at Week 12 (Observed Cases)
    End point description
    Endoscopic improvement is defined as a decrease of >=1 point in a modified endoscopic subscore or an absolute endoscopy score of <=1 without friability. All subjects who had received at least one dose of the randomized treatment were included in the analysis population. Subjects with missing values were handled by observed case approach (the missing data were used as is). The number of subjects with observed data were 8 for the Placebo + Infliximab arm and 7 for PF-06687234 20 mg + Infliximab arm. The percentage of subjects achieving endoscopic improvement was calculated based on the number of subjects with observed data.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    8
    7
    Units: Percentage of subjects (%)
        number (confidence interval 95%)
    25.0 (4.6 to 65.1)
    57.1 (22.5 to 87.1)
    Statistical analysis title
    		 Treatment Difference Between 2 Arms
    Comparison groups
    Placebo + Infliximab v PF-06687234 20 mg + Infliximab
    Number of subjects included in analysis
    15
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3166
    Method
    		 Chan and Zhang (1999)
    Parameter type
    		 Treatment difference
    Point estimate
    32.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.7
         upper limit
    		 74.1

    Secondary: Percentage of Subjects With Endoscopic Improvement at Week 12 ( Treatment Failure Approach)

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    End point title
    		 Percentage of Subjects With Endoscopic Improvement at Week 12 ( Treatment Failure Approach)
    End point description
    Endoscopic improvement is defined as a decrease of >=1 point in a modified endoscopic subscore or an absolute endoscopy score of <=1 without friability. Subjects with missing values were handled by treatment failure approach (subjects who had missing value for any reasons were considered as treatment failures). All subjects who had received at least one dose of the randomized treatment were included in the analysis population.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    10
    10
    Units: Percentage of subjects (%)
        number (confidence interval 95%)
    20.0 (3.7 to 55.6)
    40.0 (15.0 to 73.3)
    Statistical analysis title
    		 Treatment Difference Between 2 Arms
    Comparison groups
    Placebo + Infliximab v PF-06687234 20 mg + Infliximab
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5234
    Method
    		 Chan and Zhang (1999)
    Parameter type
    		 Treatment difference
    Point estimate
    20
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.9
         upper limit
    		 58.5

    Secondary: Change from Baseline in Geboes Ulcerative Colitis Score at Week 12 (Baseline Observation Carried Forward [BOCF])

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    End point title
    		 Change from Baseline in Geboes Ulcerative Colitis Score at Week 12 (Baseline Observation Carried Forward [BOCF])
    End point description
    Geboes scores is a structured six-grade classification system ordered as follows: 0, structural changes; 1, chronic inflammatory infiltrate; 2, lamina propria neutrophils and eosinophils; 3, neutrophils in epithelium; 4, crypt destruction; and 5, erosion and ulceration. Robart’s histology scores is based on the Geboes scores, and the final score is obtained by combining the sub-scores of four main items (chronic inflammatory infiltrate level, lamina propria neutrophils, neutrophils in the epithelium, and erosion or ulceration), which are classified from 0 to 3, yielding a final score that ranges between 0 and 5.4. The BOCF approach was used to handle the monotone missing data or no post baseline measurements. The baseline values were carried forward for the visits after which subjects prematurely discontinued assigned treatment. All subjects who had received at least one dose of the randomized treatment were included in the analysis population.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    10
    10
    Units: Scores on a scale
        least squares mean (confidence interval 95%)
    -10.08 (-16.95 to -3.20)
    -6.02 (-12.90 to 0.85)
    Statistical analysis title
    		 Treatment Difference Between 2 Arms
    Comparison groups
    Placebo + Infliximab v PF-06687234 20 mg + Infliximab
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3928
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean difference
    Point estimate
    4.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.7
         upper limit
    		 13.8

    Secondary: Change from Baseline in Robart's Histology Index at Week 12 (Observed Cases)

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    End point title
    		 Change from Baseline in Robart's Histology Index at Week 12 (Observed Cases)
    End point description
    Robart’s histology scores is based on the Geboes scores, and the final score is obtained by combining the sub-scores of four main items (chronic inflammatory infiltrate level, lamina propria neutrophils, neutrophils in the epithelium, and erosion or ulceration), which are classified from 0 to 3, yielding a final score that ranges between 0 and 33. All subjects who had received at least one dose of the randomized treatment were included in the analysis population. Subjects with missing values were handled by observed case approach (the missing data were used as is). The number of subjects with observed data at Week 12 were 8 each for the Placebo + Infliximab arm and PF-06687234 20mg + Infliximab arm.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    8
    8
    Units: Scores on a scale
        least squares mean (confidence interval 95%)
    -12.96 (-20.60 to -5.32)
    -7.16 (-14.81 to 0.48)
    Statistical analysis title
    		 Treatment Difference Between 2 Arms
    Comparison groups
    Placebo + Infliximab v PF-06687234 20 mg + Infliximab
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2705
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean difference
    Point estimate
    5.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.08
         upper limit
    		 16.67

    Secondary: Percentage of Subjects With a Clinical Response at Week 12 (Observed Cases)

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    End point title
    		 Percentage of Subjects With a Clinical Response at Week 12 (Observed Cases)
    End point description
    Clinical response is defined with a decrease from baseline of at least 3 points in total Mayo score with at least 30% change, accompanied by at least one-point decrease or absolute score of 0 or 1 in rectal bleeding subscore. All subjects who had received at least one dose of the randomized treatment were included in the analysis population. Subjects with missing values were handled by observed case approach (the missing data were used as is). The number of subjects with observed data were 8 for the Placebo + Infliximab arm and 7 for PF-06687234 20mg + Infliximab arm. The percentage of subjects achieving clinical response was calculated based on the number of subjects analyzed.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    8
    7
    Units: Percentage of subjects (%)
        number (confidence interval 95%)
    37.5 (11.1 to 71.1)
    85.7 (44.6 to 99.3)
    Statistical analysis title
    		 Treatment Difference Between 2 Arms
    Comparison groups
    Placebo + Infliximab v PF-06687234 20 mg + Infliximab
    Number of subjects included in analysis
    15
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0732
    Method
    		 Chan and Zhang (1999)
    Parameter type
    		 Treatment difference
    Point estimate
    48.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.4
         upper limit
    		 84.7

    Secondary: Percentage of Subjects With a Clinical Response at Week 12 (Treatment Failure Approach)

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    End point title
    		 Percentage of Subjects With a Clinical Response at Week 12 (Treatment Failure Approach)
    End point description
    Clinical response is defined with a decrease from baseline of at least 3 points in total Mayo score with at least 30% change, accompanied by at least one-point decrease or absolute score of 0 or 1 in rectal bleeding subscore. All subjects who had received at least one dose of the randomized treatment were included in the analysis population. Subjects with missing values were handled by treatment failure approach (subjects who had missing value for any reasons were considered as treatment failures).
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    10
    10
    Units: Percentage of subjects (%)
        number (confidence interval 95%)
    30.0 (8.7 to 61.9)
    60.0 (26.7 to 85.0)
    Statistical analysis title
    		 Treatment Difference Between 2 Arms
    Comparison groups
    Placebo + Infliximab v PF-06687234 20 mg + Infliximab
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2633
    Method
    		 Chan and Zhang (1999)
    Parameter type
    		 Treatment difference
    Point estimate
    30
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.4
         upper limit
    		 69.2

    Secondary: Percentage of Subjects With Change From Baseline in Derived Partial Mayo Score of <=2 With no Individual Subscore >1 at Weeks 2, 4, 8 and 12 (Observed Cases)

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    End point title
    		 Percentage of Subjects With Change From Baseline in Derived Partial Mayo Score of <=2 With no Individual Subscore >1 at Weeks 2, 4, 8 and 12 (Observed Cases)
    End point description
    Derived partial mayo score is defined as total mayo score excluding the endoscopic subscore (stool frequency, rectal bleeding and physician's global assessment only), ranging from 0 to 9. All subjects who had received at least one dose of the randomized treatment were included in the analysis population. Subjects with missing values were handled by observed case approach (the missing data were used as is). Generalized Linear Mixed Model (GLMM) was used with fixed effects of treatment, visit and treatment by visit interaction. n=number of subjects with change from baseline.
    End point type
    Secondary
    End point timeframe
    Baseline, weeks 2, 4, 8 and 12
    End point values
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    10
    10
    Units: Percentage of subjects (%)
    number (confidence interval 95%)
        Week 2 (n=10, 10)
    50.0 (21.0 to 79.0)
    50.0 (21.0 to 79.0)
        Week 4 (n=10, 10)
    50.0 (21.0 to 79.0)
    60.0 (27.9 to 85.3)
        Week 8 (n=9, 9)
    62.5 (28.9 to 87.2)
    50.8 (20.9 to 80.1)
        Week 12 (n=8, 7)
    64.9 (29.8 to 89.0)
    64.8 (28.6 to 89.4)
    Statistical analysis title
    		 Treatment Difference Between 2 Arms
    Statistical analysis description
    At Week 2
    Comparison groups
    Placebo + Infliximab v PF-06687234 20 mg + Infliximab
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 1
    Method
    		 Generalized Linear Mixed Model
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.15
         upper limit
    		 6.54
    Statistical analysis title
    		 Treatment Difference Between 2 Arms
    Statistical analysis description
    At Week 4
    Comparison groups
    Placebo + Infliximab v PF-06687234 20 mg + Infliximab
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6691
    Method
    		 Generalized Linear Mixed Model
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.23
         upper limit
    		 10
    Statistical analysis title
    		 Treatment Difference Between 2 Arms
    Statistical analysis description
    At Week 8
    Comparison groups
    Placebo + Infliximab v PF-06687234 20 mg + Infliximab
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6248
    Method
    		 Generalized Linear Mixed Model
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.09
         upper limit
    		 4.4
    Statistical analysis title
    		 Treatment Difference Between 2 Arms
    Statistical analysis description
    At Week 12
    Comparison groups
    Placebo + Infliximab v PF-06687234 20 mg + Infliximab
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9965
    Method
    		 Generalized Linear Mixed Model
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.12
         upper limit
    		 8.3

    Secondary: Serum concentrations of PF-06687234 20 mg

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    End point title
    		 Serum concentrations of PF-06687234 20 mg [6]
    End point description
    Samples for serum PF-06687234 concentration were collected at timepoints defined by the protocol. Concentration values below the lower limit of quantification were excluded when calculating the geometric mean (geometric coefficient of variation). All subjects who received at least one dose of PF-06687234, had data on at least one PK concentration (above or equal to lower limit of quantification) and did not participate in PK substudy were included in the analysis. NALQ=number of subjects with observations above or equal to lower limit of quantification. There were no subjects with qualified data for the analysis on Day 1, at Weeks 1 and 16, hence the results were entered as 99999 (not available).
    End point type
    Secondary
    End point timeframe
    Prior to dosing on Day 1, at Weeks 1, 3, 7, 11, 12 (168 hours post dose) and 16
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The PK data reporting is not applicable for the placebo arm.
    End point values
    		 PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    10
    Units: nanogram/milliliter (ng/mL)
    geometric mean (geometric coefficient of variation)
        Day 1 (NALQ=0)
    99999 ( 99999 )
        Week 1 (NALQ=0)
    99999 ( 99999 )
        Week 3 (NALQ=2)
    0.4537 ( 42 )
        Week 7 (NALQ=6)
    0.4494 ( 27 )
        Week 11 (NALQ=3)
    0.4713 ( 2 )
        Week 12 (NALQ=3)
    0.5140 ( 40 )
        Week 16 (NALQ=0)
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With the Development of Human Anti-Fusion Antibodies (HAFAs) and Neutralizing Antibodies (NAbs) Against PF-06687234

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    End point title
    		 Percentage of Subjects With the Development of Human Anti-Fusion Antibodies (HAFAs) and Neutralizing Antibodies (NAbs) Against PF-06687234 [7]
    End point description
    Plasma samples were analyzed for anti PF-06687234, anti PF-06687234 Interleukin-10 (IL-10) NAb and anti PF-06687234 single chain variable fragment (scFv) NAb. Samples inadvertently analyzed were excluded. All subjects who received at least one dose of PF-06687234 and with at least one post treatment HAFA determination were included in the analysis population. N=number of subjects with observed data. The percentages of subjects with the development of HAFAs and NAbs against PF-06687234 were calculated based on the number of subjects with observed data.
    End point type
    Secondary
    End point timeframe
    At screening, Day 1, Weeks 3, 7, 11, 12 and 16 (prior to dosing)
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The percentage of subjects with the development of HAFAs and NAbs against PF-06687234 did not apply to the placebo arm.
    End point values
    		 PF-06687234 20 mg + Infliximab
    Number of subjects analysed
    10
    Units: Percentage of subjects (%)
    number (not applicable)
        Anti PF-06687234 (Screening; N=10)
    0
        Anti PF-06687234 (Day 1; N=10)
    10.0
        Anti PF-06687234 (Week 3; N=10)
    30.0
        Anti PF-06687234 (Week 7; N=8)
    50.0
        Anti PF-06687234 (Week 11; N=7)
    28.6
        Anti PF-06687234 (Week 12; N=7)
    28.6
        Anti PF-06687234 (Week 16; N=8)
    12.5
        Anti PF-06687234 IL-10 NAb (Screening; N=0)
    0
        Anti PF-06687234 IL-10 NAb (Day 1; N=1)
    0
        Anti PF-06687234 IL-10 NAb (Week 3; N=3)
    0
        Anti PF-06687234 IL-10 NAb (Week 7; N=4)
    0
        Anti PF-06687234 IL-10 NAb (Week 11; N=2)
    0
        Anti PF-06687234 IL-10 NAb (Week 12; N=2)
    0
        Anti PF-06687234 IL-10 NAb (Week 16; N=1)
    0
        Anti PF-06687234 scFv NAb (Screening; N=0)
    0
        Anti PF-06687234 scFv NAb (Day 1; N=1)
    0
        Anti PF-06687234 scFv NAb (Week 3; N=3)
    0
        Anti PF-06687234 scFv NAb (Week 7; N=4)
    50.0
        Anti PF-06687234 scFv NAb (Week 11; N=2)
    0
        Anti PF-06687234 scFv NAb (Week 12; N=2)
    0
        Anti PF-06687234 scFv NAb (Week 16; N=1)
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the time the subject provided informed consent through approximately Week 26. For subjects who were screen failures, the active collection period ended when screen failure status was determined.
    Adverse event reporting additional description
    All 20 subjects were included in the analysis for AEs and SAEs.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Placebo + Infliximab
    Reporting group description
    		 Placebo for PF‑06687234 was administered as subcutaneous injection on Day 1, Week 1 (Day 8), Week 2 (Day 15), Week 3 (Day 22), Week 4 (Day 29), Week 5 (Day 36), Week 6 (Day 43), Week 7 (Day 50), Week 8 (Day 57), Week 9 (Day 64), Week 10 (Day 71) and Week 11 (Day 78) for a total 12 doses. Remicade or protocol specified infliximab biosimilar was administered as an IV infusion on Day 1, Week 8 and Week 16 for a total of 3 doses for subjects on infliximab every 8 weeks, and Day 1, Week 6, Week 12 and Week 18 for subjects on infliximab every 6 weeks.

    Reporting group title
    PF-06687234 20 mg + Infliximab
    Reporting group description
    		 PF-06687234 was administered as a 20 mg subcutaneous injection on Day 1, Week 1 (Day 8), Week 2 (Day 15), Week 3 (Day 22), Week 4 (Day 29), Week 5 (Day 36), Week 6 (Day 43), Week 7 (Day 50), Week 8 (Day 57), Week 9 (Day 64), Week 10 (Day 71) and Week 11 (Day 78) for a total 12 doses. Remicade or protocol specified infliximab biosimilar was administered as an IV infusion on Day 1, Week 8 and Week 16 for a total of 3 doses for subjects on infliximab every 8 weeks, and Day 1, Week 6, Week 12 and Week 18 for subjects on infliximab every 6 weeks.

    Serious adverse events
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Gastrointestinal disorders
    Colitis ulcerative
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo + Infliximab PF-06687234 20 mg + Infliximab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 10 (70.00%)
    9 / 10 (90.00%)
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 10 (20.00%)
         occurrences all number
    0
    2
    Fatigue
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    6
    Injection site reaction
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 10 (30.00%)
         occurrences all number
    0
    7
    Injection site erythema
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Oedema
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Xerosis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Injection site rash
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Vulvovaginal discomfort
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Stress
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Investigations
    Cardiac murmur
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    2 / 10 (20.00%)
    2 / 10 (20.00%)
         occurrences all number
    2
    3
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Abdominal pain lower
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Dyspepsia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Colitis ulcerative
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Gastritis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Proctalgia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Glossitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Diabetic nephropathy
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Micturition urgency
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Endocrine disorders
    Cushingoid
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Neck pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Muscle spasms
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Influenza
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Onychomycosis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Tooth infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Urinary tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 10 (20.00%)
         occurrences all number
    1
    3
    Metabolism and nutrition disorders
    Vitamin B12 deficiency
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Sep 2017
    1. Throughout the protocol modified language to allow the use of specific infliximab biosimilars; 2. Added Appendix 5 Protocol Specific Infliximab Biosimilars; 3. Changed the collection of the serum infliximab concentration and ADA against infliximab from Visit 8 Week 7 to Visit 9 Week 8; 4. Modified inclusion criterion #7 to provide further clarification regarding the infliximab treatment regimen that is required at study entry and throughout the study; 5. Modified exclusion criteria #24 hemoglobin level from <=95 g/L (9.5 g/dL) to <=100 g/L (10.0 g/dL); 6. Modified Prohibited Medications to further clarify and cover the timeframe that iTNF treatment or biologic therapy other than infliximab iTNF treatment that would be prohibited during the study, and to correct typographical error and duplicative language; 7. Modified the collection time for Plasma PF‑06687234 concentration sample at Week 12/Early Withdrawal Visit; 8. Removed automatic hemoglobin retesting criteria to limit the number of blood draws and leave it up to discretion of investigator regarding retesting necessity and timing; 9. Provided additional guidance to regulators and investigators on individual subject discontinuation criteria for specific AST or ALT results when co-occurring with specific symptoms; 10. Added the following specific language in Section 6.4 to further protect patient safety and to establish requirement for prompt ad‑hoc IRC review meetings in setting where a severe AE or an SAE is assessed as potentially causally related to the investigational product have been met and the required notification to relevant regulatory authorities regarding the ad‑hoc IRC meeting and relevant case details; 11. Added Reference: Schroeder KW, Tremaine WJ and Listrup DM. NEJM 1987;24;317(26) 1625-1629.
    06 Mar 2018
    Updated enrollment and safety information in Philogen Dekavil RA study; 2. Deleted “or legally acceptable representative” in Criterion #1 and in Sections 8.1.2 and 12.3; 3. Modified the inclusion criterion #3 to add “weight >40 kg”; 4. Added exclusion criterion #30 to exclude subjects who had known history of hypersensitivity, intolerance or allergic reaction to IP or any constituent of the IP; 5. Updated the exclusion criterion #18 to protect safety of the study subjects and comply with regulatory request; 6. Section 4.4.1 Contraception: Removed ‘using male or female condom plus spermicide as a highly effective method of contraception’ and modified the contraception requirement to ‘2 methods of contraception (at least one of which is considered to be highly effective)’; 7. Section 4.4.1 Contraception: Added “Male subjects must refrain from sperm donation for the duration of the active treatment period and until Week 16 or 28 days after the last dose of the investigational product.; 8. Added a new subsection 5.11 Rescue Medication to provide clarification that rescue therapy should be provided by investigators as deemed clinically appropriate and that subjects requiring rescue medication will be discontinued from the study; 9. Clarified in the Section 5.2 Breaking the Blind that if the immediate unblinding is necessary, the discussion between investigator and the member of study team member is not required in advance of unblinding; 10. Clarified that IP and placebo are prepared by qualified unblinded site staff and administration of prepared IP or placebo to subjects is performed by qualified blinded site staff; 11. Added a discontinuation criterion that a subject with detected neutralizing antibody against IL‑10 domain will be discontinued from the treatment and the study; 12. Replaced the reference #22 with “Chan ISF., Zhang Z. Test-based exact confidence intervals for the difference of two binomial proportions. Biometrics, 1999; 55: 1201–1209.”
    30 Aug 2018
    Safety related: 1.Added text for subject discontinuation in the presence of detectable NAb against IL‑10 portion of PF‑06687432 in Schedule of Activities; 2. Widened the interval between infliximab infusion completion and IP dosing; 3. Provided rationale, references, and practice guidance to allow infliximab dosing every 6 weeks in the protocol; 4. Changed to allow subjects on infliximab dosing interval of every 6 weeks into the study and clarified the time requirement for study eligibility after change of infliximab regimen (dosage and dosing interval); 5. Modified the criterion to state “Subjects who have partial response to anti‑TNF (infliximab) and active UC as defined by (via screening endoscopy) a total Mayo Score >=4 but <=9 and an endoscopic subscore >=2; 6. Modified inclusion criterion #6 to allow the inclusion of subjects with disease severity consistent with other inclusion criteria whilst still excluding subjects with isolated proctitis; 7. Modified exclusion criterion 4 to clarify that a colonoscopy is required for subjects with extensive colitis and without surveillance colonoscopy within 2 years and that this surveillance can be performed during the screening colonoscopy if necessary; 8. Clarified the exclusion criterion #5 that subjects with prior history of adenomatous polyps will be eligible if the polyps have been completely removed and pathology is negative; 9. Section 4.2, exclusion criterion#24: Changed the exclusion criterion eGFR to <60 mL/min/1.73 mm^2 based on age appropriate calculation; 10. Revised exclusion criterion is to exclude subjects with evidence of active TB or latent TB patients without adequate treatment into the study; 11. Updated with newly available 6 months toxicity data in mice and revised the safety margin based on clinical dose of 0.5 mg/kg/week.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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