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    Clinical Trial Results:
    A Randomized, Placebo-Controlled, Double-Blind, Multicenter Study to Assess the Efficacy and Safety of Branebrutinib Treatment in Subjects with Active Systemic Lupus Erythematosus or Primary Sjögren’s Syndrome, or Branebrutinib Treatment Followed by Open-label Abatacept Treatment in Subjects with Active Rheumatoid Arthritis

    Summary
    EudraCT number
    		 2019-002205-22
    Trial protocol
    		 GB   FR   BE   ES   PL   NL   DE  
    Global end of trial date
    05 Dec 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    24 Dec 2023
    First version publication date
    24 Dec 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    IM014-029
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04186871
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussée de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Organization Name: Bristol-Myers Squibb, Clinical.Trials@bms.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
    21 Mar 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    05 Dec 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Dec 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    - To compare the efficacy of branebrutinib with PBO at Week 24 in the treatment of subjects with SLE and pSS. - To compare the efficacy of branebrutinib with PBO at Week 12 in the treatment of subjects with moderate to severe RA on a stable background of MTX who have had an inadequate response to MTX
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 Jan 2020
    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
    Argentina: 4
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    France: 1
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    Mexico: 8
    Country: Number of subjects enrolled
    Poland: 62
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    United States: 32
    Worldwide total number of subjects
    119
    EEA total number of subjects
    75
    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)
    113
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants were enrolled concurrently for the RA, SLE, and pSS sub-studies.119 Participants were treated.

    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, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 SLE- Placebo
    Arm description
    		 Participants with systemic lupus erythematosus (SLE) receive placebo once daily (QD) during a 24-week double-blind placebo-controlled treatment period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    PBO matching Branebrutinib oral capsule

    Arm title
    		 SLE- Branebrutinib
    Arm description
    		 Participants with systemic lupus erythematosus (SLE) receive branebrutinib 9mg once daily (QD) during a 24-week double-blind placebo-controlled treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Branebrutinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    3 mg dose × 3 capsules (9 mg total dose)

    Arm title
    		 pSS- Placebo
    Arm description
    		 Participants with primary Sjögren’s syndrome (pSS) receive placebo once daily (QD) during a 24-week double-blind placebo-controlled treatment period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    PBO matching Branebrutinib oral capsule

    Arm title
    		 pSS- Branebrutinib
    Arm description
    		 Participants with primary Sjögren’s syndrome (pSS) receive branebrutinib 9mg once daily (QD) during a 24-week double-blind placebo-controlled treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Branebrutinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    3 mg dose × 3 capsules (9 mg total dose)

    Arm title
    		 RA- Placebo
    Arm description
    		 Participants with rheumatoid arthritis (RA) receive placebo once daily (QD) during a 12-week double-blind placebo-controlled treatment period, followed by an additional 12 weeks of treatment with open-label abatacept.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    PBO matching Branebrutinib oral capsule

    Arm title
    		 RA- Branebrutinib
    Arm description
    		 Participants with rheumatoid arthritis (RA) receive branebrutinib 9mg once daily (QD) during a 12-week double-blind placebo-controlled treatment period, followed by an additional 12 weeks of treatment with open-label abatacept.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Branebrutinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    3 mg dose × 3 capsules (9 mg total dose)

    Number of subjects in period 1
    		SLE- Placebo SLE- Branebrutinib pSS- Placebo pSS- Branebrutinib RA- Placebo RA- Branebrutinib
    Started
    5
    15
    4
    10
    21
    64
    Double Blind Period
    5
    15
    4
    10
    21
    64
    Open Label Period
    0 [1]
    0 [2]
    0 [3]
    0 [4]
    20
    61
    Completed
    3
    11
    4
    9
    20
    58
    Not completed
    2
    4
    0
    1
    1
    6
         Consent withdrawn by subject
    -
    -
    -
    -
    -
    1
         Adverse event, non-fatal
    1
    1
    -
    -
    -
    2
         Study terminated by sponsor
    1
    2
    -
    1
    -
    -
         Other reasons
    -
    -
    -
    -
    -
    1
         Lost to follow-up
    -
    -
    -
    -
    -
    1
         Lack of efficacy
    -
    1
    -
    -
    1
    1
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only RA participants had the Open-Label option.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only RA participants had the Open-Label option.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only RA participants had the Open-Label option.
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only RA participants had the Open-Label option.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    SLE- Placebo
    Reporting group description
    		 Participants with systemic lupus erythematosus (SLE) receive placebo once daily (QD) during a 24-week double-blind placebo-controlled treatment period.

    Reporting group title
    SLE- Branebrutinib
    Reporting group description
    		 Participants with systemic lupus erythematosus (SLE) receive branebrutinib 9mg once daily (QD) during a 24-week double-blind placebo-controlled treatment period.

    Reporting group title
    pSS- Placebo
    Reporting group description
    		 Participants with primary Sjögren’s syndrome (pSS) receive placebo once daily (QD) during a 24-week double-blind placebo-controlled treatment period.

    Reporting group title
    pSS- Branebrutinib
    Reporting group description
    		 Participants with primary Sjögren’s syndrome (pSS) receive branebrutinib 9mg once daily (QD) during a 24-week double-blind placebo-controlled treatment period.

    Reporting group title
    RA- Placebo
    Reporting group description
    		 Participants with rheumatoid arthritis (RA) receive placebo once daily (QD) during a 12-week double-blind placebo-controlled treatment period, followed by an additional 12 weeks of treatment with open-label abatacept.

    Reporting group title
    RA- Branebrutinib
    Reporting group description
    		 Participants with rheumatoid arthritis (RA) receive branebrutinib 9mg once daily (QD) during a 12-week double-blind placebo-controlled treatment period, followed by an additional 12 weeks of treatment with open-label abatacept.

    Reporting group values
    		 SLE- Placebo SLE- Branebrutinib pSS- Placebo pSS- Branebrutinib RA- Placebo RA- Branebrutinib Total
    Number of subjects
    		 5 15 4 10 21 64 119
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 5 14 4 10 21 59 113
        From 65-84 years
    		 0 1 0 0 0 5 6
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 47.6 ± 10.99 44.2 ± 12.91 47.8 ± 4.19 46.6 ± 9.28 46.0 ± 12.95 50.1 ± 11.62 -
    Sex: Female, Male
    Units: Participants
        Female
    		 5 14 4 7 18 45 93
        Male
    		 0 1 0 3 3 19 26
    Race/Ethnicity, Customized
    Units: Subjects
        Asian - Non-Japanese
    		 0 0 0 0 0 2 2
        Black or African American
    		 1 3 0 0 0 2 6
        White
    		 2 6 4 9 21 59 101
        Not Reported
    		 0 0 0 1 0 1 2
        American Indian or Alaska Native
    		 2 6 0 0 0 0 8
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 3 9 0 1 1 7 21
        Not Hispanic or Latino
    		 2 6 4 8 20 57 97
        Unknown or Not Reported
    		 0 0 0 1 0 0 1

    End points

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    End points reporting groups
    Reporting group title
    SLE- Placebo
    Reporting group description
    		 Participants with systemic lupus erythematosus (SLE) receive placebo once daily (QD) during a 24-week double-blind placebo-controlled treatment period.

    Reporting group title
    SLE- Branebrutinib
    Reporting group description
    		 Participants with systemic lupus erythematosus (SLE) receive branebrutinib 9mg once daily (QD) during a 24-week double-blind placebo-controlled treatment period.

    Reporting group title
    pSS- Placebo
    Reporting group description
    		 Participants with primary Sjögren’s syndrome (pSS) receive placebo once daily (QD) during a 24-week double-blind placebo-controlled treatment period.

    Reporting group title
    pSS- Branebrutinib
    Reporting group description
    		 Participants with primary Sjögren’s syndrome (pSS) receive branebrutinib 9mg once daily (QD) during a 24-week double-blind placebo-controlled treatment period.

    Reporting group title
    RA- Placebo
    Reporting group description
    		 Participants with rheumatoid arthritis (RA) receive placebo once daily (QD) during a 12-week double-blind placebo-controlled treatment period, followed by an additional 12 weeks of treatment with open-label abatacept.

    Reporting group title
    RA- Branebrutinib
    Reporting group description
    		 Participants with rheumatoid arthritis (RA) receive branebrutinib 9mg once daily (QD) during a 12-week double-blind placebo-controlled treatment period, followed by an additional 12 weeks of treatment with open-label abatacept.

    Primary: The Percent of Participants with mCLASI Response at Week 24 and Corticosteroid (CS) < 10 mg/day at Week 20 and Week 24 - SLE

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    End point title
    		 The Percent of Participants with mCLASI Response at Week 24 and Corticosteroid (CS) < 10 mg/day at Week 20 and Week 24 - SLE [1]
    End point description
    mCLASI response is defined as a decrease of ≥ 50% from baseline mCLASI activity score, in participants with a baseline mCLASI activity score ≥ 10, at Week 24. Baseline values are defined as the last nonmissing value prior to the first dose of study treatment. To be considered as meeting the second criterion, the CS (prednisone or equivalent) dose had to remain stable and ≤ 10 mg from Week 16 until Week 24. The modified CLASI (mCLASI) is defined as the activity portions of CLASI that describe skin erythema and scale/hypertrophy and inflammation of the scalp. The percentage of patients who entered the study with a positive mCLASI activity score (≥ 10) and who achieved a ≥ 50% decrease from baseline at Week 24 is considered to likely represent a clinically meaningful improvement. The scores are calculated by simple addition based on the extent of the symptoms. mCLASI: Modified Cutaneous Lupus Erythematosus Disease Area and Severity Index
    End point type
    Primary
    End point timeframe
    Week 24
    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: Endpoint is Specific only to the SLE Cohort
    End point values
    		 SLE- Placebo SLE- Branebrutinib
    Number of subjects analysed
    5
    15
    Units: Percentage of participants
        number (confidence interval 95%)
    60.0 (17.1 to 100)
    33.3 (9.5 to 57.2)
    Statistical analysis title
    		 ODDS RATIO (95% CI) VS PLACEBO
    Comparison groups
    SLE- Placebo v SLE- Branebrutinib
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3117
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.04
         upper limit
    		 2.73
    Statistical analysis title
    		 RESPONSE DIFFERENCE (95% CI) VS PLACEBO
    Comparison groups
    SLE- Placebo v SLE- Branebrutinib
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Response Difference
    Point estimate
    -27.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -77.5
         upper limit
    		 21.9

    Primary: The Percent of Participants with Composite Response at Week 24 - pSS

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    End point title
    		 The Percent of Participants with Composite Response at Week 24 - pSS [2]
    End point description
    Composite response is defined as the percent of participants with at least 3 of the following at Week 24: • Decrease of ≥ 1 point or 15% from baseline in the ESSPRI Total Score • Decrease of ≥ 3 points from baseline in ESSDAI score • Decrease of ≥ 25% from baseline in ocular staining score, or if normal score at baseline no change to abnormal • Increase of ≥ 25% from baseline in stimulated salivary flow • Improvement in one or more serological markers (rheumatoid factor (RF), immunoglobulin G protein (IgG), complement C3 or C4, cryoglobulin).
    End point type
    Primary
    End point timeframe
    Week 24
    Notes
    [2] - 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: Endpoint is Specific only to the pSS Cohort
    End point values
    		 pSS- Placebo pSS- Branebrutinib
    Number of subjects analysed
    4
    10
    Units: Percent of Participants
        number (confidence interval 95%)
    25 (0.0 to 67.4)
    10.0 (0.0 to 28.6)
    Statistical analysis title
    		 ODDS RATIO VS PLACEBO
    Comparison groups
    pSS- Placebo v pSS- Branebrutinib
    Number of subjects included in analysis
    14
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.1639
    Method
    		 Chi-squared
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.15
         upper limit
    		 1.39
    Statistical analysis title
    		 RESPONSE DIFFERENCE (95% CI) VS PLACEBO
    Comparison groups
    pSS- Placebo v pSS- Branebrutinib
    Number of subjects included in analysis
    14
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Response Difference
    Point estimate
    -11.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -57.1
         upper limit
    		 33.3

    Primary: Percent of Participants with ACR50 Response at Week 12 Compared to Baseline - RA

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    End point title
    		 Percent of Participants with ACR50 Response at Week 12 Compared to Baseline - RA [3]
    End point description
    ACR50 response is defined as both improvement of 50% in the number of tender and swollen joints and a 50% improvement in 3 of the following 5 criteria: - Subject global assessment (SGA) - Physician global assessment (PGA) - Functional ability measure - Pain visual analog scale (VAS) - Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Baseline values are defined as the last nonmissing value prior to the first dose of study treatment.
    End point type
    Primary
    End point timeframe
    Week 12
    Notes
    [3] - 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: Endpoint is Specific only to the RA Cohort
    End point values
    		 RA- Placebo RA- Branebrutinib
    Number of subjects analysed
    21
    64
    Units: Percent of Participants
        number (confidence interval 95%)
    33.3 (13.2 to 53.5)
    18.8 (9.2 to 28.3)
    Statistical analysis title
    		 ODDS RATIO VS PLACEBO
    Comparison groups
    RA- Placebo v RA- Branebrutinib
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1639
    Method
    		 Chi-squared
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.15
         upper limit
    		 1.39
    Statistical analysis title
    		 RESPONSE DIFFERENCE VS PLACEBO
    Comparison groups
    RA- Placebo v RA- Branebrutinib
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Response Difference
    Point estimate
    -14.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -36.9
         upper limit
    		 7.7

    Secondary: Change from Baseline in SLEDAI-2K Score at Week 24 - SLE

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    End point title
    		 Change from Baseline in SLEDAI-2K Score at Week 24 - SLE [4]
    End point description
    The SLEDAI-2K is a global index providing a total score of overall disease activity ranging from 0 to 105, with higher scores representing more active disease. The SLEDAI index includes 24 items divided into 9 organ systems: neurological, musculoskeletal, renal, mucocutaneous, general, heart, respiratory, vascular, and hematological. Each item is scored based on the severity of the symptom or finding, with higher scores indicating more severe disease activity. The weighted scores for each item range from 0 to 8. To calculate the SLEDAI-2K score, the scores for each of the 24 items are added together. Baseline values are defined as the last nonmissing value prior to the first dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [4] - 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: Endpoint is Specific only to the SLE Cohort
    End point values
    		 SLE- Placebo SLE- Branebrutinib
    Number of subjects analysed
    4
    11
    Units: Change in "score on a scale"
        arithmetic mean (standard deviation)
    -7.0 ± 5.29
    -7.0 ± 6.54
    Statistical analysis title
    		 ADJUSTED MEAN DIFFERENCE VS PLACEBO
    Comparison groups
    SLE- Placebo v SLE- Branebrutinib
    Number of subjects included in analysis
    15
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.8
         upper limit
    		 4.9

    Secondary: Percent of Participants with BICLA Response at Week 24 - SLE

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    End point title
    		 Percent of Participants with BICLA Response at Week 24 - SLE [5]
    End point description
    BILAG-based composite lupus assessment (BICLA) response is defined as: 1. At least one gradation of improvement in baseline BILAG scores in all body systems with moderate or severe disease activity at entry 2. No new BILAG A or more than one new BILAG B scores 3. No worsening of total SLEDAI score from baseline 4. No significant deterioration (< 10%) in PGA and 5. No treatment failure (initiation of nonprotocol treatment). BILAG scores: A (severe disease), B (moderate), C (mild), or D (no activity). Baseline values are defined as the last nonmissing value prior to the first dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [5] - 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: Endpoint is Specific only to the SLE Cohort
    End point values
    		 SLE- Placebo SLE- Branebrutinib
    Number of subjects analysed
    5
    15
    Units: Percent of participants
        number (confidence interval 95%)
    20.0 (0.5 to 71.6)
    33.3 (11.8 to 61.6)
    Statistical analysis title
    		 ODDS RATIO VS PLACEBO
    Comparison groups
    SLE- Placebo v SLE- Branebrutinib
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.22
         upper limit
    		 18.04
    Statistical analysis title
    		 RESPONSE DIFFERENCE VS PLACEBO
    Comparison groups
    SLE- Placebo v SLE- Branebrutinib
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Response Difference
    Point estimate
    16.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -31.8
         upper limit
    		 65.2

    Secondary: Change from Baseline in DAS28-CRP at Week 12 - RA

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    End point title
    		 Change from Baseline in DAS28-CRP at Week 12 - RA [6]
    End point description
    The Disease Activity Score-28-C-Reactive Protein (DAS28CRP) is a composite outcome assessment that measures: 1) How many joints in the hands, wrists, elbows, shoulders, and knees are swollen and/or tender over a total of 28, 2) CRP in the blood to measure the degree of inflammation, and 3) SGA of disease activity. DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. The results are combined to produce the DAS28-CRP score, which correlates with the extent of disease activity: < 2.6: Disease remission 2.6 – 3.2: Low disease activity 3.2 – 5.1: Moderate disease activity > 5.1: High disease activity A negative change from baseline in DAS28-CRP indicates an improvement. Baseline values are defined as the last nonmissing value prior to the first dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Week 12
    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: Endpoint is Specific only to the RA Cohort
    End point values
    		 RA- Placebo RA- Branebrutinib
    Number of subjects analysed
    19
    58
    Units: Score on a scale
        arithmetic mean (standard deviation)
    -1.615 ± 1.19545
    -1.542 ± 1.0790
    Statistical analysis title
    		 ADJUSTED MEAN DIFFERENCE VS PLACEBO
    Comparison groups
    RA- Placebo v RA- Branebrutinib
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.043
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.534
         upper limit
    		 0.62

    Secondary: Change from baseline in SDAI at Week 12- RA

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    End point title
    		 Change from baseline in SDAI at Week 12- RA [7]
    End point description
    The Simplified Disease Activity Index (SDAI) is the sum of the tender joint score (range 0 to 28), the swollen joint score (range 0 to 28), the subject global assessment (SGA) of disease activity (range 0 to 10 in increments of 0.5), the PGA of disease activity (range 0 to 10 in increments of 0.5), and C-reactive protein (CRP) test result. Baseline values are defined as the last nonmissing value prior to the first dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Week 12
    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: Endpoint is Specific only to the RA Cohort
    End point values
    		 RA- Placebo RA- Branebrutinib
    Number of subjects analysed
    19
    58
    Units: Score on a scale
        arithmetic mean (standard deviation)
    -19.430 ± 12.5890
    -18.303 ± 11.5793
    Statistical analysis title
    		 ADJUSTED MEAN DIFFERENCE VS PLACEBO
    Comparison groups
    RA- Placebo v RA- Branebrutinib
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.728
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.463
         upper limit
    		 6.919

    Secondary: Change from baseline in DAS28-ESR at Week 12 - RA

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    End point title
    		 Change from baseline in DAS28-ESR at Week 12 - RA [8]
    End point description
    The Disease Activity Score Erythrocyte Sedimentation Rate - DAS28ESR is a composite outcome assessment that measures: 1) How many joints in the hands, wrists, elbows, shoulders, and knees are swollen and/or tender over a total of 28 2) ESR in the blood to measure the degree of inflammation 3) SGA of disease activity DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. The results are combined to produce the DAS28-ESR score, which correlates with the extent of disease activity: < 2.6: Disease remission 2.6 – 3.2: Low disease activity 3.2 – 5.1: Moderate disease activity > 5.1: High disease activity A negative change from baseline in DAS28-ESR indicates an improvement. Baseline values are defined as the last nonmissing value prior to the first dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [8] - 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: Endpoint is Specific only to the RA Cohort
    End point values
    		 RA- Placebo RA- Branebrutinib
    Number of subjects analysed
    20
    58
    Units: Score on a scale
        arithmetic mean (standard deviation)
    -1.758 ± 1.1932
    -1.670 ± 1.1487
    Statistical analysis title
    		 ADJUSTED MEAN DIFFERENCE VS PLACEBO
    Comparison groups
    RA- Placebo v RA- Branebrutinib
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.043
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.553
         upper limit
    		 0.639

    Secondary: Percent of Participants with ACR20 Response Compared to Baseline at Week 12 - RA

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    End point title
    		 Percent of Participants with ACR20 Response Compared to Baseline at Week 12 - RA [9]
    End point description
    ACR20 defined as both improvement of 20% in the number of tender and swollen joints and a 20% improvement in 3 of the following 5 criteria: - Subject global assessment (SGA) - Physician global assessment (PGA) - Functional ability measure - Pain visual analog scale (VAS) - Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Baseline values are defined as the last nonmissing value prior to the first dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [9] - 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: Endpoint is Specific only to the RA Cohort
    End point values
    		 RA- Placebo RA- Branebrutinib
    Number of subjects analysed
    21
    64
    Units: Percent of Participants
        number (confidence interval 95%)
    61.9 (41.1 to 82.7)
    57.8 (45.7 to 69.9)
    Statistical analysis title
    		 ODDS RATIO VS PLACEBO
    Comparison groups
    RA- Placebo v RA- Branebrutinib
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.31
         upper limit
    		 2.32
    Statistical analysis title
    		 RESPONSE DIFFERENCE VS PLACEBO
    Comparison groups
    RA- Placebo v RA- Branebrutinib
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Response Difference
    Point estimate
    -4.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.1
         upper limit
    		 19.9

    Secondary: Change from baseline in CDAI at Week 12 - RA

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    End point title
    		 Change from baseline in CDAI at Week 12 - RA [10]
    End point description
    The Clinical Disease Activity Index (CDAI) is the sum of the tender joint score (range 0 to 28), the swollen joint score (range 0 to 28), the SGA of disease activity (range 0 to 10 in increments of 0.5), and the PGA of disease activity (range 0 to 10 in increments of 0.5). Baseline values are defined as the last nonmissing value prior to the first dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [10] - 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: Endpoint is Specific only to the RA Cohort
    End point values
    		 RA- Placebo RA- Branebrutinib
    Number of subjects analysed
    20
    58
    Units: Score on a scale
        arithmetic mean (standard deviation)
    -19.4 ± 12.07
    -18.0 ± 11.01
    Statistical analysis title
    		 ADJUSTED MEAN DIFFERENCE VS PLACEBO
    Comparison groups
    RA- Placebo v RA- Branebrutinib
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.2
         upper limit
    		 6.6

    Secondary: Percent of Participants with ACR70 Response Compared to Baseline at Week 12 - RA

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    End point title
    		 Percent of Participants with ACR70 Response Compared to Baseline at Week 12 - RA [11]
    End point description
    ACR70 is defined as both improvement of 70% in the number of tender and swollen joints and a 70% improvement in 3 of the following 5 criteria: - Subject global assessment (SGA) - Physician global assessment (PGA) - Functional ability measure - Pain visual analog scale (VAS) - Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Baseline values are defined as the last nonmissing value prior to the first dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [11] - 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: Endpoint is Specific only to the RA Cohort
    End point values
    		 RA- Placebo RA- Branebrutinib
    Number of subjects analysed
    21
    64
    Units: Percent of Participants
        number (confidence interval 95%)
    14.3 (0.0 to 29.3)
    7.8 (1.2 to 14.4)
    Statistical analysis title
    		 RESPONSE DIFFERENCE VS PLACEBO
    Comparison groups
    RA- Placebo v RA- Branebrutinib
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Response Difference
    Point estimate
    -6.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.8
         upper limit
    		 9.9
    Statistical analysis title
    		 ODDS RATIO VS PLACEBO
    Comparison groups
    RA- Placebo v RA- Branebrutinib
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.11
         upper limit
    		 2.34

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality was assessed from participants first dose to their study completion (up to approximately 32 weeks) SAEs and Other AEs were assessed from first dose to 30 days following last dose (up to approximately 30 weeks)
    Adverse event reporting additional description
    TEAEs are defined as AEs that occur after the participant received first dose of study treatment or if a preexisting condition worsens in severity or becomes serious after receiving the first dose of study treatment up to 30 days after the last dose of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    SLE- Placebo
    Reporting group description
    		 Participants with systemic lupus erythematosus (SLE) receive placebo once daily (QD) during a 24-week double-blind placebo-controlled treatment period.

    Reporting group title
    SLE- Branebrutinib
    Reporting group description
    		 Participants with systemic lupus erythematosus (SLE) receive branebrutinib 9mg once daily (QD) during a 24-week double-blind placebo-controlled treatment period.

    Reporting group title
    pSS- Placebo
    Reporting group description
    		 Participants with primary Sjögren’s syndrome (pSS) receive placebo once daily (QD) during a 24-week double-blind placebo-controlled treatment period.

    Reporting group title
    RA- Abatacept
    Reporting group description
    		 Participants with rheumatoid arthritis (RA) receive 12 weeks of treatment with open-label abatacept.

    Reporting group title
    RA- Placebo
    Reporting group description
    		 Participants with rheumatoid arthritis (RA) receive placebo once daily (QD) during a 12-week double-blind placebo-controlled treatment period, followed by an additional 12 weeks of treatment with open-label abatacept.

    Reporting group title
    RA- Branebrutinib
    Reporting group description
    		 Participants with rheumatoid arthritis (RA) receive branebrutinib 9mg once daily (QD) during a 12-week double-blind placebo-controlled treatment period.

    Reporting group title
    pSS- Branebrutinib
    Reporting group description
    		 Participants with primary Sjögren’s syndrome (pSS) receive branebrutinib 9mg once daily (QD) during a 24-week double-blind placebo-controlled treatment period.

    Serious adverse events
    		 SLE- Placebo SLE- Branebrutinib pSS- Placebo RA- Abatacept RA- Placebo RA- Branebrutinib pSS- Branebrutinib
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 SLE- Placebo SLE- Branebrutinib pSS- Placebo RA- Abatacept RA- Placebo RA- Branebrutinib pSS- Branebrutinib
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 5 (80.00%)
    14 / 15 (93.33%)
    4 / 4 (100.00%)
    5 / 81 (6.17%)
    6 / 21 (28.57%)
    13 / 64 (20.31%)
    8 / 10 (80.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Injection site swelling
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Discomfort
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Asthenia
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    1 / 64 (1.56%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Psychiatric disorders
    Stress
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Investigations
    Neutrophil count decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Gastric pH decreased
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    1 / 21 (4.76%)
    1 / 64 (1.56%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    1
    Injury, poisoning and procedural complications
    Face injury
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Animal scratch
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Ligament sprain
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    1 / 64 (1.56%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    1
    0
    Scratch
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Vaccination complication
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    2 / 10 (20.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Sunburn
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 4 (25.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    Cardiac disorders
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Nervous system disorders
    Somnolence
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    2 / 21 (9.52%)
    1 / 64 (1.56%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    2
    1
    0
    Headache
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    1 / 4 (25.00%)
    1 / 81 (1.23%)
    1 / 21 (4.76%)
    1 / 64 (1.56%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    1
    1
    1
    1
    1
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    Eye disorders
    Ocular hyperaemia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Dry eye
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    1 / 81 (1.23%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    Nausea
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Enterocolitis
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Gastritis
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    1 / 64 (1.56%)
    2 / 10 (20.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    2
    Urticaria
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    Drug eruption
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    1 / 21 (4.76%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    Bursitis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    1 / 4 (25.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    1 / 81 (1.23%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    COVID-19
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    2 / 21 (9.52%)
    5 / 64 (7.81%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    5
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    1 / 21 (4.76%)
    2 / 64 (3.13%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    2
    0
    Pharyngotonsillitis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Otitis media acute
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    3 / 4 (75.00%)
    1 / 81 (1.23%)
    1 / 21 (4.76%)
    1 / 64 (1.56%)
    2 / 10 (20.00%)
         occurrences all number
    0
    3
    3
    1
    1
    1
    2
    Hordeolum
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Gastroenteritis
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 15 (13.33%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 5 (0.00%)
    3 / 15 (20.00%)
    0 / 4 (0.00%)
    1 / 81 (1.23%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    3
    0
    1
    0
    0
    1
    Metabolism and nutrition disorders
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 15 (0.00%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    1 / 64 (1.56%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Dyslipidaemia
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 15 (6.67%)
    0 / 4 (0.00%)
    0 / 81 (0.00%)
    0 / 21 (0.00%)
    0 / 64 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Oct 2019
    Updated RA sub-protocol to exclude combination therapy of branebrutinib and abatacept, revised timing period for collection of nonserious AEs in all sub-protocols, updated and aligned branebrutinib PK sampling schedule in all sub-protocols to accommodate change in RA protocol design
    18 Dec 2019
    Updated RA sub-protocol to include omitted joint assessor instructions, Updated all sub-protocols to current BMS standards for reproductive status inclusion criteria
    30 Mar 2021
    Added section for study termination for unexpectedly unfavorable risk/benefit balance; added information/guidance related to SARS-CoV-2 infection/COVID-19 pandemic, changed the maximum age of the study population; clarified CS requirements (SLE sub-protocol only); excluded subjects with diagnosis of antiphospholipid syndrome from SLE sub-protocol, etc
    01 Dec 2021
    Changed timing for primary endpoint and other efficacy, safety, PK, and PD analysis for the RA sub-protocol; included patient-reported outcome assessments as Additional endpoints in all 3 sub-protocols; updated unintentionally omitted changes in inclusion criteria in RA sub-protocol schema; clarified PK and biomarker blood samples to be collected for abatacept and branebrutinib, respectively, at Week 24 in the RA sub-protocol; added unintentionally omitted biomarker blood sample collections for BTK occupancy from Week 0 to Week 12 in the RA sub-protocol.

    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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    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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