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    Clinical Trial Results:
    A Phase 2 Study to Evaluate the Efficacy and Safety of LY3462817 in Participants with Moderately to Severely Active Rheumatoid Arthritis

    Summary
    EudraCT number
    		 2020-002673-10
    Trial protocol
    		 CZ   HU   PL  
    Global end of trial date
    29 Jun 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    12 Jul 2023
    First version publication date
    22 Jan 2023
    Other versions
    		 v1
    Version creation reason
    • New data added to full data set
    Final data to be posted

    Trial information

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    Trial identification
    Sponsor protocol code
    J1A-MC-KDAD
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04634253
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 17424
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,
    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
    29 Jun 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Jun 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The reason for this study is to see if the study drug LY3462817 is safe and effective in participants with moderately to severely active rheumatoid arthritis (RA).
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    04 Jan 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Hungary: 28
    Country: Number of subjects enrolled
    United States: 18
    Country: Number of subjects enrolled
    Czechia: 4
    Country: Number of subjects enrolled
    Poland: 18
    Country: Number of subjects enrolled
    Mexico: 30
    Worldwide total number of subjects
    98
    EEA total number of subjects
    50
    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)
    84
    From 65 to 84 years
    14
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 No Text Available

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received (0.9% sodium chloride solution) Placebo administered Intravenously.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    0.9% sodium chloride solution was administered as an IV infusion.

    Arm title
    		 LY3462817 300 mg
    Arm description
    		 Participants received 300 milligrams (mg) of LY3462817 administered Intravenously.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LY3462817
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg of LY3462817 administered as an IV infusion in 50 mg/mL in a 3-mL vial.

    Arm title
    		 LY3462817 700 mg
    Arm description
    		 Participants received 700 mg of LY3462817 administered Intravenously.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LY3462817
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    700 mg of LY3462817 administered as an IV infusion in 50 mg/mL in a 3-mL vial.

    Number of subjects in period 1
    		Placebo LY3462817 300 mg LY3462817 700 mg
    Started
    24
    25
    49
    Completed
    22
    23
    46
    Not completed
    2
    2
    3
         Consent withdrawn by subject
    1
    -
    3
         Physician decision
    -
    1
    -
         Adverse event, non-fatal
    1
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received (0.9% sodium chloride solution) Placebo administered Intravenously.

    Reporting group title
    LY3462817 300 mg
    Reporting group description
    		 Participants received 300 milligrams (mg) of LY3462817 administered Intravenously.

    Reporting group title
    LY3462817 700 mg
    Reporting group description
    		 Participants received 700 mg of LY3462817 administered Intravenously.

    Reporting group values
    		 Placebo LY3462817 300 mg LY3462817 700 mg Total
    Number of subjects
    		 24 25 49 98
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 55.8 ( 11.1 ) 50.1 ( 15.8 ) 50.5 ( 11.2 ) -
    Gender categorical
    Units: Subjects
        Female
    		 19 20 43 82
        Male
    		 5 5 6 16
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 7 10 13 30
        Asian
    		 0 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        Black or African American
    		 0 0 2 2
        White
    		 17 15 34 66
        More than one race
    		 0 0 0 0
        Unknown or Not Reported
    		 0 0 0 0
    Region of Enrollment
    Units: Subjects
        Hungary
    		 8 5 15 28
        United States
    		 4 5 9 18
        Czechia
    		 0 3 1 4
        Poland
    		 5 2 11 18
        Mexico
    		 7 10 13 30

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received (0.9% sodium chloride solution) Placebo administered Intravenously.

    Reporting group title
    LY3462817 300 mg
    Reporting group description
    		 Participants received 300 milligrams (mg) of LY3462817 administered Intravenously.

    Reporting group title
    LY3462817 700 mg
    Reporting group description
    		 Participants received 700 mg of LY3462817 administered Intravenously.

    Primary: Change from Baseline on the Disease Activity Score Modified to Include the 28 Diarthrodial Joint Count–High-Sensitivity C-Reactive Protein (DAS28-hsCRP)

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    End point title
    		 Change from Baseline on the Disease Activity Score Modified to Include the 28 Diarthrodial Joint Count–High-Sensitivity C-Reactive Protein (DAS28-hsCRP)
    End point description
    Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56*square root (sqrt) (TJC28) plus (+) 0.28*sqrt (SJC28)+ 0.014* participant's global assessment of disease activity + 0.36*natural log(hsCRP+1) +0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity. Least Square Mean (LS Mean) was calculated using mixed model repeated measures (MMRM) with treatment, strata (previous RA therapy population), baseline value, visit, treatment-by-visit interaction as fixed factors. Analysis Population Description (APD): All randomized participants who received at least one dose and had data for DAS28-hsCRP
    End point type
    Primary
    End point timeframe
    Baseline, Week 12
    End point values
    		 Placebo LY3462817 300 mg LY3462817 700 mg
    Number of subjects analysed
    20
    22
    42
    Units: Units on a scale
        least squares mean (standard error)
    -0.99 ( 0.261 )
    -1.88 ( 0.249 )
    -2.09 ( 0.184 )
    Statistical analysis title
    		 Change from Baseline on the DAS28-hsCRP
    Comparison groups
    Placebo v LY3462817 300 mg
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.017
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean
    Point estimate
    -0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 -0.16
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.361
    Statistical analysis title
    		 Change from Baseline on the DAS28-hsCRP
    Comparison groups
    Placebo v LY3462817 700 mg
    Number of subjects included in analysis
    62
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean
    Point estimate
    -1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.73
         upper limit
    		 -0.46
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.32

    Secondary: Percentage of Participants Achieving 20% Improvement in American College of Rheumatology Criteria (ACR20)

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    End point title
    		 Percentage of Participants Achieving 20% Improvement in American College of Rheumatology Criteria (ACR20)
    End point description
    ACR responders are participants with at least 20% improvement from baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) which measures participants perceived degree of difficulty performing daily activities, acute phase reactant as measured by hsCRP, Patient's Assessment of Pain-Visual Analog Scale (Pain-VAS), Patient’s Global Assessment of Disease Activity (PaGADA_VAS), and Physician’s Global Assessment of Disease Activity (PhGADA_VAS). APD: All randomized participants.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo LY3462817 300 mg LY3462817 700 mg
    Number of subjects analysed
    24
    25
    49
    Units: Percentage of Participants
        number (confidence interval 95%)
    41.7 (21.9 to 61.4)
    44.0 (24.5 to 63.5)
    71.4 (58.8 to 84.1)
    Statistical analysis title
    		 Percentage of Participants Achieving ACR20
    Comparison groups
    Placebo v LY3462817 300 mg
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.997
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.29
         upper limit
    		 3.44
    Statistical analysis title
    		 Percentage of Participants Achieving ACR20
    Comparison groups
    Placebo v LY3462817 700 mg
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.032
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.11
         upper limit
    		 10.4

    Secondary: Percentage of Participants Achieving 70% Improvement in American College of Rheumatology Criteria (ACR70)

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    End point title
    		 Percentage of Participants Achieving 70% Improvement in American College of Rheumatology Criteria (ACR70)
    End point description
    ACR responders are participants with at least 70% improvement from baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) which measures participants perceived degree of difficulty performing daily activities, acute phase reactant as measured by hsCRP, Patient's Assessment of Pain-Visual Analog Scale (Pain-VAS), Patient’s Global Assessment of Disease Activity (PaGADA_VAS), and Physician’s Global Assessment of Disease Activity (PhGADA_VAS). APD: All randomized participants.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo LY3462817 300 mg LY3462817 700 mg
    Number of subjects analysed
    24
    25
    49
    Units: Percentage of Participants
        number (confidence interval 95%)
    16.7 (1.8 to 31.6)
    4.0 (0 to 11.7)
    20.4 (9.1 to 31.7)
    Statistical analysis title
    		 Percentage of Participants Achieving ACR70
    Comparison groups
    Placebo v LY3462817 300 mg
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.235
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.04
         upper limit
    		 2.25
    Statistical analysis title
    		 Percentage of Participants Achieving ACR70
    Comparison groups
    Placebo v LY3462817 700 mg
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.661
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.33
         upper limit
    		 5.61

    Secondary: Percentage of Participants Achieving 50% Improvement in American College of Rheumatology Criteria (ACR50)

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    End point title
    		 Percentage of Participants Achieving 50% Improvement in American College of Rheumatology Criteria (ACR50)
    End point description
    ACR responders are participants with at least 50% improvement from baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) which measures participants perceived degree of difficulty performing daily activities, acute phase reactant as measured by hsCRP, Patient's Assessment of Pain-Visual Analog Scale (Pain-VAS), Patient’s Global Assessment of Disease Activity (PaGADA_VAS), and Physician’s Global Assessment of Disease Activity (PhGADA_VAS). APD: All randomized participants.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo LY3462817 300 mg LY3462817 700 mg
    Number of subjects analysed
    24
    25
    49
    Units: Percentage of Participants
        number (confidence interval 95%)
    20.8 (4.6 to 37.1)
    20.0 (4.3 to 35.7)
    38.8 (25.1 to 52.4)
    Statistical analysis title
    		 Percentage of Participants Achieving ACR50
    Comparison groups
    Placebo v LY3462817 300 mg
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.965
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.22
         upper limit
    		 4.28
    Statistical analysis title
    		 Percentage of Participants Achieving ACR50
    Comparison groups
    Placebo v LY3462817 700 mg
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.098
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 10.33

    Secondary: Change from Baseline for Mean Simplified Disease Activity Index (SDAI)

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    End point title
    		 Change from Baseline for Mean Simplified Disease Activity Index (SDAI)
    End point description
    The SDAI is a tool for measurement of disease activity in RA that integrates measures of physical examination, acute phase response, patient self-assessment, and evaluator assessment. The SDAI is calculated by adding together scores from 1) TJC28 (0 to 28), 2) SJC28 (0 to 28), 3) acute phase response using C-reactive protein (0.1 to 10.0 mg/dL), 4) Patient's Global Assessment of Disease Activity using VAS (0 to 10 cm), and 5) Physician's Global Assessment of Disease Activity using VAS (0 to 10 cm). Total Score scale range is 0 (remission) to 86 (high disease activity). LS Mean was calculated using mixed model repeated measures (MMRM) with treatment, strata (previous RA therapy population), baseline value, visit, treatment-by-visit interaction as fixed factors. APD: All randomized participants who received at least one dose and had data for SDAI.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    		 Placebo LY3462817 300 mg LY3462817 700 mg
    Number of subjects analysed
    20
    21
    42
    Units: units on a scale
        least squares mean (standard error)
    -13.80 ( 2.664 )
    -25.06 ( 2.571 )
    -26.90 ( 1.880 )
    Statistical analysis title
    		 Change from Baseline for SDAI
    Comparison groups
    Placebo v LY3462817 300 mg
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -11.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.65
         upper limit
    		 -3.87
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.71
    Statistical analysis title
    		 Change from Baseline for SDAI
    Comparison groups
    Placebo v LY3462817 700 mg
    Number of subjects included in analysis
    62
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -13.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.61
         upper limit
    		 -6.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.265

    Secondary: Change from Baseline for Mean Clinical Disease Activity Index (CDAI)

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    End point title
    		 Change from Baseline for Mean Clinical Disease Activity Index (CDAI)
    End point description
    The CDAI is a tool for measurement of disease activity in RA that does not require a laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). The CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity. A negative change from baseline indicates improvement in condition. LS Mean was calculated using MMRM with treatment, strata (previous RA therapy population), baseline value, visit, treatment-by-visit interaction as fixed factors.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    		 Placebo LY3462817 300 mg LY3462817 700 mg
    Number of subjects analysed
    20
    21
    44
    Units: units on a scale
        least squares mean (standard error)
    -13.75 ( 2.709 )
    -24.06 ( 2.628 )
    -25.51 ( 1.854 )
    Statistical analysis title
    		 Change from Baseline for CDAI
    Comparison groups
    Placebo v LY3462817 300 mg
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.008
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -10.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.83
         upper limit
    		 -2.77
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.782
    Statistical analysis title
    		 Change from Baseline for CDAI
    Comparison groups
    Placebo v LY3462817 700 mg
    Number of subjects included in analysis
    64
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -11.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.29
         upper limit
    		 -5.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.282

    Secondary: Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute)

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    End point title
    		 Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute)
    End point description
    The SF-36 is a health-related survey that assesses participant's health status and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health, mental health, social functioning, and vitality. The 8 domains are combined to form 2 component scores mental (MCS) and physical (PCS). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status. LS mean was determined by ANCOVA with factors for treatment and previous RA therapy population included as fixed factors,
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    		 Placebo LY3462817 300 mg LY3462817 700 mg
    Number of subjects analysed
    21
    23
    47
    Units: Units on a scale
    least squares mean (standard error)
        PCS
    5.01 ( 1.711 )
    7.03 ( 1.633 )
    6.43 ( 1.165 )
        MCS
    3.48 ( 1.715 )
    0.55 ( 1.630 )
    4.64 ( 1.166 )
    Statistical analysis title
    		 Mental Component Score (MCS)
    Comparison groups
    Placebo v LY3462817 300 mg
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.218
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.63
         upper limit
    		 1.77
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.365
    Statistical analysis title
    		 Mental Component Score (MCS)
    Comparison groups
    Placebo v LY3462817 700 mg
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.578
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.95
         upper limit
    		 5.26
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.065
    Statistical analysis title
    		 Physical Component Score (PCS)
    Comparison groups
    Placebo v LY3462817 300 mg
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.396
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    2.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.69
         upper limit
    		 6.73
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.368

    Secondary: Pharmacokinetics (PK): Observed Concentration of LY3462817

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    End point title
    		 Pharmacokinetics (PK): Observed Concentration of LY3462817 [1]
    End point description
    PK: Observed Concentration of LY3462817
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [1] - 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: PK analysis is for LY3462817
    End point values
    		 LY3462817 300 mg LY3462817 700 mg
    Number of subjects analysed
    25
    49
    Units: nanograms per milliliter
        median (confidence interval 95%)
    7970 (1290 to 17100)
    15600 (1820 to 36600)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline, up to Week 12
    Adverse event reporting additional description
    All randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    LY3462817 700 mg
    Reporting group description
    		 -

    Reporting group title
    LY3462817 300 mg
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo LY3462817 700 mg LY3462817 300 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Endocrine disorders
    hypothyroidism
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (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: 0%
    Non-serious adverse events
    		 Placebo LY3462817 700 mg LY3462817 300 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 24 (37.50%)
    13 / 49 (26.53%)
    8 / 25 (32.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    b-cell lymphoma
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 49 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    0
    Investigations
    weight increased
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 49 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    1
    Vascular disorders
    hypertension
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 49 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    0
    Surgical and medical procedures
    tooth extraction
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 49 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    0
    Nervous system disorders
    allodynia
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 49 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    1
    dizziness
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 49 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    1
    headache
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    hypoaesthesia
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    General disorders and administration site conditions
    fatigue
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 49 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    0
    pyrexia
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    Gastrointestinal disorders
    diarrhoea
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    nausea
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    4 / 49 (8.16%)
    0 / 25 (0.00%)
         occurrences all number
    0
    4
    0
    vomiting
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    Skin and subcutaneous tissue disorders
    dermatitis atopic
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    onychoclasis
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 49 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    0
    pruritus
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    1
    3
    0
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    back pain
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    osteoarthritis
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    rheumatoid arthritis
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 49 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    0
    Infections and infestations
    covid-19
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    1 / 25 (4.00%)
         occurrences all number
    0
    1
    1
    gastroenteritis
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 49 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    1
    helicobacter infection
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 49 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    1
    herpes simplex
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 49 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    0
    mastitis
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 49 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    1
    nasopharyngitis
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 49 (2.04%)
    2 / 25 (8.00%)
         occurrences all number
    1
    1
    2
    rhinitis
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    sinusitis
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 49 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    1
    skin bacterial infection
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 49 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    1
    tooth abscess
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 49 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    0
    upper respiratory tract infection
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    urinary tract infection
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    upper respiratory tract infection bacterial
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    vulvovaginal candidiasis
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed [1]
    0 / 19 (0.00%)
    1 / 43 (2.33%)
    0 / 20 (0.00%)
         occurrences all number
    0
    1
    0
    Metabolism and nutrition disorders
    diabetes mellitus
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    dyslipidaemia
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    2 / 24 (8.33%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    2
    1
    0
    hyperglycaemia
    alternative dictionary used: MedDRA 25.0
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 49 (2.04%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Sep 2020
    Protocol Amendment (a) • Participants on placebo will not be allowed to crossover to LY3462817 at any point during the study. • Added requirement of an Interim Analysis of Study KDAC data collected prior to proceeding to Period 2. • Standard of Care (SOC) therapy to be allowed to begin at Week 14. • All participants on placebo will receive SOC starting at Week 14 (Visit 7). • Removed Rescue Therapy wording • Patients who do not achieve Low Disease Activity will be removed from LY3462817 and switched to standard of care. • Patients who do achieve Low Disease Activity will be allowed LY3462817 until week 24.
    11 Dec 2020
    Protocol amendment (b): The protocol was amended to clarify study procedures and statistical considerations.

    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.
    No adjustment for multiplicity was made. For assessments beyond the primary endpoint, nominal p-values are reported.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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