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    Clinical Trial Results:
    ASCEND GO 2: A Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled Study of RVT 1401 for the Treatment of Patients with Active, Moderate to Severe Graves’ Ophthalmopathy

    Summary
    EudraCT number
    		 2018-004676-35
    Trial protocol
    		 DE   ES   IT  
    Global end of trial date
    15 Apr 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Sep 2022
    First version publication date
    09 Sep 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    RVT-1401-2001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03938545
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Immunovant Sciences GmbH
    Sponsor organisation address
    Viaduktstrasse 8, Basel, Switzerland, 4051
    Public contact
    Central Study Contact, Immunovant Sciences GmbH, +1 800-797-0414, clinicaltrials@immunovant.com
    Scientific contact
    Central Study Contact, Immunovant Sciences GmbH, +1 800-797-0414, clinicaltrials@immunovant.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
    23 May 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    02 Feb 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Apr 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objectives of this study was to examine the effects of RVT-1401 versus placebo on proptosis responder rate at Week 13 and to assess the safety and tolerability of RVT-1401 in participants with active, moderate to severe Graves' Ophthalmopathy (GO)
    Protection of trial subjects
    The study was conducted in accordance with the principles of the Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and South Africa), International Council for Harmonisation (ICH) guidelines, and all of the applicable basic principles of “Good Clinical Practice,” as outlined in 21 CFR 312, subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, part 50, 1998, and 21 CFR, part 56, 1998. These standards were consistent with the requirements of the European Community Directive 2001/20/EC.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 Jul 2019
    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
    Canada: 3
    Country: Number of subjects enrolled
    Germany: 38
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    United States: 18
    Worldwide total number of subjects
    65
    EEA total number of subjects
    44
    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)
    63
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 96 participants were screened, of which 65 participants were enrolled and randomized into the study. The total duration of the study was up to 20 weeks.

    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
    		 RVT-1401 680 mg/week
    Arm description
    		 Participants received a RVT-1401 680 milligram (mg) subcutaneous (SC) injection weekly for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    batoclimab
    Investigational medicinal product code
    RVT-1401
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received 680 mg. Doses were prepared by an unblinded pharmacist or designee. Doses were administered to participants by pre-identified unblinded clinic staff or designee.

    Arm title
    		 RVT-1401 340 mg/week
    Arm description
    		 Participants received a RVT-1401 340 mg SC injection weekly for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    batoclimab
    Investigational medicinal product code
    RVT-1401
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received 340 mg. Doses were prepared by an unblinded pharmacist or designee. Doses were administered to participants by pre-identified unblinded clinic staff or designee.

    Arm title
    		 RVT-1401 255 mg/week
    Arm description
    		 Participants received a RVT-1401 255 mg SC injection weekly for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    batoclimab
    Investigational medicinal product code
    RVT-1401
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received 255 mg. Doses were prepared by an unblinded pharmacist or designee. Doses were administered to participants by pre-identified unblinded clinic staff or designee.

    Arm title
    		 Placebo
    Arm description
    		 Participants received a matching placebo SC injection weekly for 12 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Placebo
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received matched placebo. Doses were prepared by an unblinded pharmacist or designee. Doses were administered to participants by pre-identified unblinded clinic staff or designee.

    Number of subjects in period 1
    		RVT-1401 680 mg/week RVT-1401 340 mg/week RVT-1401 255 mg/week Placebo
    Started
    18
    19
    10
    18
    Completed
    10
    14
    7
    13
    Not completed
    8
    5
    3
    5
         Consent withdrawn by subject
    -
    1
    -
    -
         Adverse event, non-fatal
    1
    -
    -
    -
         Study Terminated By Sponsor
    6
    4
    2
    4
         Pregnancy
    1
    -
    -
    -
         Non-Compliance With Study Drug
    -
    -
    1
    -
         Lost to follow-up
    -
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    RVT-1401 680 mg/week
    Reporting group description
    		 Participants received a RVT-1401 680 milligram (mg) subcutaneous (SC) injection weekly for 12 weeks.

    Reporting group title
    RVT-1401 340 mg/week
    Reporting group description
    		 Participants received a RVT-1401 340 mg SC injection weekly for 12 weeks.

    Reporting group title
    RVT-1401 255 mg/week
    Reporting group description
    		 Participants received a RVT-1401 255 mg SC injection weekly for 12 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received a matching placebo SC injection weekly for 12 weeks.

    Reporting group values
    		 RVT-1401 680 mg/week RVT-1401 340 mg/week RVT-1401 255 mg/week Placebo Total
    Number of subjects
    		 18 19 10 18 65
    Age categorical
    Units:
    Age continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 46.6 ± 9.03 52.4 ± 8.08 44.3 ± 12.61 46.1 ± 12.47 -
    Gender categorical
    Units: Subjects
        Female
    		 15 13 8 14 50
        Male
    		 3 6 2 4 15
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0
        Asian
    		 0 0 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 0 0 0 0 0
        White
    		 17 18 10 18 63
        More than one race
    		 0 0 0 0 0
        Unknown or Not Reported
    		 1 1 0 0 2
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 1 2 0 0 3
        Not Hispanic or Latino
    		 17 17 10 18 62
        Unknown or Not Reported
    		 0 0 0 0 0
    Mean Proptosis
    Units: Millimeters (mm)
        arithmetic mean (standard deviation)
    		 22.7 ± 3.10 23.0 ± 3.97 22.3 ± 2.95 22.7 ± 2.70 -
    Mean Clinical Activity Score (CAS)
    The CAS (7-item scale) measured the acute signs of inflammation like pain, redness, swelling, and impaired function in Graves' Ophthalmology (GO). One point was given for the presence of each of the parameters assessed. The CAS ranged from 0 to 7. Active GO was defined as a CAS of ≥4. Baseline was the last available assessment prior to time of the first dose unless it was specified otherwise and was identified as Day 1. A negative change from baseline represented clinical improvement.
    Units: Units on a scale
        arithmetic mean (standard deviation)
    		 4.8 ± 0.86 5.1 ± 0.94 4.9 ± 0.99 5.2 ± 1.04 -

    End points

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    End points reporting groups
    Reporting group title
    RVT-1401 680 mg/week
    Reporting group description
    		 Participants received a RVT-1401 680 milligram (mg) subcutaneous (SC) injection weekly for 12 weeks.

    Reporting group title
    RVT-1401 340 mg/week
    Reporting group description
    		 Participants received a RVT-1401 340 mg SC injection weekly for 12 weeks.

    Reporting group title
    RVT-1401 255 mg/week
    Reporting group description
    		 Participants received a RVT-1401 255 mg SC injection weekly for 12 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received a matching placebo SC injection weekly for 12 weeks.

    Primary: Percentage of participants with proptosis response at Week 13

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    End point title
    		 Percentage of participants with proptosis response at Week 13
    End point description
    Proptosis was assessed using an exophthalmometer. A proptosis response was defined as having at least a 2 millimeter (mm) reduction in study eye proptosis without a deterioration (at least a 2 mm increase) in the fellow eye at the same visit. The study eye was defined as the most severely affected eye at the baseline visit. The analysis was performed in Intent-to-Treat (ITT) Population: All randomized participants who received at least one dose of RVT-1401 or placebo and had 1 post-baseline visit. Participants with proptosis assessment at Week 13 were included in the analysis.
    End point type
    Primary
    End point timeframe
    Baseline; Week 13
    End point values
    		 RVT-1401 680 mg/week RVT-1401 340 mg/week RVT-1401 255 mg/week Placebo
    Number of subjects analysed
    10
    13
    6
    12
    Units: Percentage of participants
        number (not applicable)
    30.0
    30.8
    0
    8.3
    Statistical analysis title
    		 Risk Difference: RVT 1401 680 mg/week vs Placebo
    Statistical analysis description
    The risk difference was obtained from a weighted average of the difference within each stratum using Cochran Mantel-Haenszel weights.
    Comparison groups
    RVT-1401 680 mg/week v Placebo
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1993 [1]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    21.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.3
         upper limit
    		 54.1
    Notes
    [1] - p-values were obtained from a Mantel-Haenszel test stratified by smoking status at baseline comparing RVT-1401 680 mg/Week group to placebo.
    Statistical analysis title
    		 Risk Difference: RVT 1401 340 mg/week vs Placebo
    Statistical analysis description
    The risk difference was obtained from a weighted average of the difference within each stratum using Cochran Mantel-Haenszel weights.
    Comparison groups
    RVT-1401 340 mg/week v Placebo
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1016 [2]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    24.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 53.2
    Notes
    [2] - p-values were obtained from a Mantel-Haenszel test stratified by smoking status at baseline comparing RVT-1401 340 mg/Week group to placebo.
    Statistical analysis title
    		 Risk Difference: RVT 1401 255 mg/week vs Placebo
    Statistical analysis description
    The risk difference was obtained from a weighted average of the difference within each stratum using Cochran Mantel-Haenszel weights.
    Comparison groups
    RVT-1401 255 mg/week v Placebo
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2963 [3]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -8.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24
         upper limit
    		 7.3
    Notes
    [3] - p-values were obtained from a Mantel-Haenszel test stratified by smoking status at baseline comparing RVT-1401 255 mg/Week group to placebo.

    Primary: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs)

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    End point title
    		 Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs) [4]
    End point description
    AEs - any untoward medical occurrences in a participant, temporally associated with use of a medicinal product, whether or not considered related to the product. Clinically significant changes determined by the Investigator such as vital signs, ECGs, and clinical laboratory values were also reported as AEs. TEAE is defined as an AE that starts on or after the first dose of the study drug and before 30 days after the last dose of the study drug. SAEs were defined as any untoward medical occurrences that: resulted in death; were life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; were congenital anomaly/birth defects; were important medical events that may have jeopardized the participant or may have required medical or surgical intervention; invasive or malignant cancers; and development of drug dependency or drug abuse.
    End point type
    Primary
    End point timeframe
    From Baseline up to Week 20
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis was performed for this safety endpoint.
    End point values
    		 RVT-1401 680 mg/week RVT-1401 340 mg/week RVT-1401 255 mg/week Placebo
    Number of subjects analysed
    18 [5]
    19
    10
    18
    Units: Participants
    number (not applicable)
        TEAEs
    16
    16
    8
    16
        SAEs
    0
    0
    1
    0
    Notes
    [5] - Safety Population: All randomized participants who received at least 1 dose of RVT-1401 or placebo.
    No statistical analyses for this end point

    Secondary: Least Square Mean Percent Change From Baseline in Binding Anti-thyroid-stimulating Hormone Receptor (TSHR) Antibody Levels to Week 13

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    End point title
    		 Least Square Mean Percent Change From Baseline in Binding Anti-thyroid-stimulating Hormone Receptor (TSHR) Antibody Levels to Week 13
    End point description
    Binding Anti-TSHR antibody serum levels are directly associated with GO clinical features. Baseline was the last available assessment prior to the time of the first dose unless it was specified otherwise and was identified as Day 1. A negative change from baseline in binding anti-TSHR antibody levels indicated therapeutic benefit. The analysis was performed in ITT Population. Participants with anti-TSHR serum assessments at Week 13 were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 13
    End point values
    		 RVT-1401 680 mg/week RVT-1401 340 mg/week RVT-1401 255 mg/week Placebo
    Number of subjects analysed
    10
    13
    6
    12
    Units: Percent change
        least squares mean (confidence interval 95%)
    -64.605 (-87.006 to -42.205)
    -69.663 (-89.272 to -50.054)
    -41.843 (-70.070 to -13.616)
    -4.520 (-25.580 to 16.539)
    Statistical analysis title
    		 LSM Difference: RVT 1401 680 mg/week vs Placebo
    Comparison groups
    RVT-1401 680 mg/week v Placebo
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [6]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -60.085
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -88.857
         upper limit
    		 -31.313
    Notes
    [6] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.
    Statistical analysis title
    		 LSM Difference: RVT 1401 340 mg/week vs Placebo
    Comparison groups
    RVT-1401 340 mg/week v Placebo
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [7]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -65.143
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -91.927
         upper limit
    		 -38.358
    Notes
    [7] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.
    Statistical analysis title
    		 LSM Difference: RVT 1401 255 mg/week vs Placebo
    Comparison groups
    RVT-1401 255 mg/week v Placebo
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0284 [8]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -37.323
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -70.455
         upper limit
    		 -4.19
    Notes
    [8] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.

    Secondary: Least Square Mean Percent Change From Baseline in Total IgG Levels

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    End point title
    		 Least Square Mean Percent Change From Baseline in Total IgG Levels
    End point description
    Blood samples we collected to determine total IgG levels. Baseline was the last available assessment prior to the time of the first dose unless it was specified otherwise and was identified as Day 1. A negative change from baseline in the IgG levels indicated therapeutic benefit. The analysis was performed in ITT Population: Participants with evaluable data were included for the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 13
    End point values
    		 RVT-1401 680 mg/week RVT-1401 340 mg/week RVT-1401 255 mg/week Placebo
    Number of subjects analysed
    10
    13
    6
    12
    Units: Grams per liter (g/L)
        least squares mean (confidence interval 95%)
    -79.101 (-86.444 to -71.757)
    -65.103 (-71.687 to -58.519)
    -57.934 (-67.216 to -48.651)
    -6.098 (-12.948 to 0.753)
    Statistical analysis title
    		 Week 13: RVT-1401 680 mg/Week, Placebo
    Comparison groups
    RVT-1401 680 mg/week v Placebo
    Number of subjects included in analysis
    22
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -73.003
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -82.309
         upper limit
    		 -63.697
    Statistical analysis title
    		 Week 13: RVT-1401 340 mg/Week, Placebo
    Comparison groups
    Placebo v RVT-1401 340 mg/week
    Number of subjects included in analysis
    25
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -59.005
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -67.821
         upper limit
    		 -50.19
    Statistical analysis title
    		 Week 13: RVT-1401 255 mg/Week, Placebo
    Comparison groups
    Placebo v RVT-1401 255 mg/week
    Number of subjects included in analysis
    18
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -51.836
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -62.66
         upper limit
    		 -41.012

    Secondary: Least Square Mean Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4

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    End point title
    		 Least Square Mean Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4
    End point description
    Blood samples were collected to determine IgG 1,2,3 and 4 levels. Baseline was the last available assessment prior to the time of the first dose unless it was specified otherwise and was identified as Day 1. A negative change from baseline in the IgG levels indicated therapeutic benefit. The analysis was performed in ITT Population. Participants with evaluable data were included for the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 13
    End point values
    		 RVT-1401 680 mg/week RVT-1401 340 mg/week RVT-1401 255 mg/week Placebo
    Number of subjects analysed
    9
    12
    5
    9
    Units: g/L
    least squares mean (confidence interval 95%)
        IgG1
    -82.040 (-90.757 to -73.323)
    -68.141 (-75.721 to -60.561)
    -67.784 (-79.273 to -56.294)
    -0.550 (-9.307 to 8.207)
        IgG2
    -75.346 (-84.395 to -66.297)
    -53.678 (-62.077 to -45.280)
    -53.879 (-65.648 to -42.110)
    -0.481 (-9.392 to 8.431)
        IgG3
    -88.260 (-98.901 to -77.619)
    -65.211 (-74.336 to -56.085)
    -66.182 (-79.856 to -52.508)
    0.503 (-9.907 to 10.914)
        IgG4
    -68.559 (-77.456 to -59.663)
    -55.391 (-63.131 to -47.651)
    -52.916 (-64.774 to -41.059)
    0.163 (-9.167 to 9.493)
    Statistical analysis title
    		 IgG1: RVT-1401 680 mg/Week, Placebo
    Comparison groups
    RVT-1401 680 mg/week v Placebo
    Number of subjects included in analysis
    18
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [9]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -81.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -93.203
         upper limit
    		 -69.777
    Notes
    [9] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.
    Statistical analysis title
    		 IgG1: RVT-1401 340 mg/Week, Placebo
    Comparison groups
    RVT-1401 340 mg/week v Placebo
    Number of subjects included in analysis
    21
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [10]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -67.591
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -78.562
         upper limit
    		 -56.62
    Notes
    [10] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.
    Statistical analysis title
    		 IgG1: RVT-1401 255 mg/Week, Placebo
    Comparison groups
    RVT-1401 255 mg/week v Placebo
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [11]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -67.233
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -81.073
         upper limit
    		 -53.394
    Notes
    [11] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.
    Statistical analysis title
    		 IgG2: RVT-1401 680 mg/Week, Placebo
    Comparison groups
    RVT-1401 680 mg/week v Placebo
    Number of subjects included in analysis
    18
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [12]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -74.865
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -86.898
         upper limit
    		 -62.832
    Notes
    [12] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.
    Statistical analysis title
    		 IgG2: RVT-1401 340 mg/Week, Placebo
    Comparison groups
    RVT-1401 340 mg/week v Placebo
    Number of subjects included in analysis
    21
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [13]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -53.198
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -64.799
         upper limit
    		 -41.596
    Notes
    [13] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.
    Statistical analysis title
    		 IgG2: RVT-1401 255 mg/Week, Placebo
    Comparison groups
    RVT-1401 255 mg/week v Placebo
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [14]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -53.398
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -67.552
         upper limit
    		 -39.245
    Notes
    [14] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.
    Statistical analysis title
    		 IgG3: RVT-1401 680 mg/Week, Placebo
    Comparison groups
    RVT-1401 680 mg/week v Placebo
    Number of subjects included in analysis
    18
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [15]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -88.764
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -103.039
         upper limit
    		 -74.489
    Notes
    [15] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.
    Statistical analysis title
    		 IgG3: RVT-1401 340 mg/Week, Placebo
    Comparison groups
    RVT-1401 340 mg/week v Placebo
    Number of subjects included in analysis
    21
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [16]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -65.714
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -78.742
         upper limit
    		 -52.686
    Notes
    [16] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.
    Statistical analysis title
    		 IgG3: RVT-1401 255 mg/Week, Placebo
    Comparison groups
    RVT-1401 255 mg/week v Placebo
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [17]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -66.685
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -83.157
         upper limit
    		 -50.214
    Notes
    [17] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.
    Statistical analysis title
    		 IgG4: RVT-1401 680 mg/Week, Placebo
    Comparison groups
    RVT-1401 680 mg/week v Placebo
    Number of subjects included in analysis
    18
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [18]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -68.722
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -80.877
         upper limit
    		 -56.568
    Notes
    [18] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.
    Statistical analysis title
    		 IgG4: RVT-1401 340 mg/Week, Placebo
    Comparison groups
    RVT-1401 340 mg/week v Placebo
    Number of subjects included in analysis
    21
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [19]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -55.554
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -67.182
         upper limit
    		 -43.926
    Notes
    [19] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.
    Statistical analysis title
    		 IgG4: RVT-1401 255 mg/Week, Placebo
    Comparison groups
    RVT-1401 255 mg/week v Placebo
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [20]
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -53.079
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -67.948
         upper limit
    		 -38.21
    Notes
    [20] - The model included baseline value of the corresponding parameter, smoking stratum, and treatment group as covariates.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Baseline up to Week 20
    Adverse event reporting additional description
    TEAE is defined as an AE that starts on or after the first dose of the study drug and before 30 days after the last dose of the study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    RVT-1401 680 mg/week
    Reporting group description
    		 Participants received a RVT-1401 680 milligram (mg) subcutaneous (SC) injection weekly for 12 weeks.

    Reporting group title
    RVT-1401 340 mg/week
    Reporting group description
    		 Participants received a RVT-1401 340 mg SC injection weekly for 12 weeks.

    Reporting group title
    RVT-1401 255 mg/week
    Reporting group description
    		 Participants received a RVT-1401 255 mg SC injection weekly for 12 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received a matching placebo SC injection weekly for 12 weeks.

    Serious adverse events
    		 RVT-1401 680 mg/week RVT-1401 340 mg/week RVT-1401 255 mg/week Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Eye disorders
    Optic neuropathy
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 RVT-1401 680 mg/week RVT-1401 340 mg/week RVT-1401 255 mg/week Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    16 / 18 (88.89%)
    16 / 19 (84.21%)
    8 / 10 (80.00%)
    16 / 18 (88.89%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypertension
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    1
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    5 / 18 (27.78%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    5
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Injection site urticaria
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Nodule
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pain
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Injection site pain
         subjects affected / exposed
    1 / 18 (5.56%)
    3 / 19 (15.79%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Chills
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Injection site bruising
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Injection site pruritus
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Fatigue
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 19 (10.53%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Injection site swelling
         subjects affected / exposed
    1 / 18 (5.56%)
    4 / 19 (21.05%)
    1 / 10 (10.00%)
    1 / 18 (5.56%)
         occurrences all number
    1
    4
    1
    1
    Injection site erythema
         subjects affected / exposed
    9 / 18 (50.00%)
    9 / 19 (47.37%)
    3 / 10 (30.00%)
    3 / 18 (16.67%)
         occurrences all number
    9
    9
    3
    3
    Reproductive system and breast disorders
    Menstruation irregular
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Menorrhagia
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dysmenorrhoea
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    1
    Investigations
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Thyroxine decreased
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Thyroxine increased
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tri-iodothyronine decreased
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tri-iodothyronine increased
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood cholesterol increased
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 19 (10.53%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Vitamin D decreased
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Intraocular pressure increased
         subjects affected / exposed
    2 / 18 (11.11%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    2
    0
    0
    2
    Injury, poisoning and procedural complications
    Accident
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Back injury
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tooth fracture
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Ligament sprain
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nervous system disorders
    Paraesthesia
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Paresis
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dysgeusia
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tension headache
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Dyspraxia
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Migraine
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Headache
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    0
    1
    Parosmia
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Lethargy
         subjects affected / exposed
    2 / 18 (11.11%)
    5 / 19 (26.32%)
    1 / 10 (10.00%)
    4 / 18 (22.22%)
         occurrences all number
    2
    5
    1
    4
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Eye disorders
    Dry eye
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Blepharitis
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Optic neuropathy
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 18 (5.56%)
    2 / 19 (10.53%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Abdominal pain
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    Aphthous ulcer
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 19 (10.53%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    2
    0
    1
    Diarrhoea
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    1 / 10 (10.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    1
    Nausea
         subjects affected / exposed
    0 / 18 (0.00%)
    4 / 19 (21.05%)
    0 / 10 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    4
    0
    2
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Neurodermatitis
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Groin pain
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Muscle spasms
         subjects affected / exposed
    1 / 18 (5.56%)
    3 / 19 (15.79%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Pain in extremity
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Osteoarthritis
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    Myalgia
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    1
    0
    0
    1
    Arthralgia
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    2 / 18 (11.11%)
         occurrences all number
    0
    0
    1
    2
    Infections and infestations
    Gastrointestinal viral infection
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Groin abscess
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Influenza
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Erythema migrans
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Fungal skin infection
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Herpes zoster
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Corona virus infection
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    1 / 10 (10.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sinusitis
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    Hordeolum
         subjects affected / exposed
    0 / 18 (0.00%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    Herpes simplex
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    1
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    1 / 10 (10.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    1
    1
    Metabolism and nutrition disorders
    Iron deficiency
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 19 (0.00%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hyperlipidaemia
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 19 (5.26%)
    0 / 10 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Feb 2019
    The following items were updated: • Definition for proptosis responder was updated to remove subjects with < 3 mm proptosis at baseline. • Additional details on method for primary analysis was added. • Additional information to note that the first interim analysis will be blinded was added. •To simplify the CAS administration, this was changed from the 10-item to the 7-item CAS. As a result, proptosis and motility assessments have been added. Other administrative changes were also made.
    09 Aug 2019
    The following items were updated: • Dosing was extended from 6 to 12 weeks. • The follow up period was shortened from 12 weeks to 8 weeks. • Associated changes related to the updated study design have also been made to the objectives and endpoints, entry criteria, and the timing of assessments in the Time and Events Table. • Additional laboratory tests were also included. • Repeat CT scans will only be completed for week 13 proptosis responders instead of for all participants. Other administrative changes were also made.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    02 Feb 2021
    The study was halted due to a safety finding (hypercholesterolemia) and not resumed.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The study was terminated early due to a safety finding (hypercholesterolemia).
    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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