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    Clinical Trial Results:
    A Phase 3, Randomized, Open-Label, Parallel-Group Study to Compare the Pharmacodynamics, Pharmacokinetics, Efficacy, Safety, Tolerability, and Immunogenicity of Multiple Subcutaneous Injections of Efgartigimod PH20 SC with Multiple Intravenous Infusions of Efgartigimod in Patients with Generalized Myasthenia Gravis

    Summary
    EudraCT number
    		 2020-004085-19
    Trial protocol
    		 HU   NL   BE   DE   IT  
    Global end of trial date
    13 Dec 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Dec 2022
    First version publication date
    15 Dec 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ARGX-113-2001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04735432
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND: 152843
    Sponsors
    Sponsor organisation name
    argenx BV
    Sponsor organisation address
    Industriepark Zwijnaarde 7, Zwijnaarde (Ghent), Belgium, 9052
    Public contact
    argenx BV, argenx BV, 32 9310 3400, regulatory@argenx.com
    Scientific contact
    argenx BV, argenx BV, 32 9310 3400, regulatory@argenx.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
    16 Aug 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    13 Dec 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Dec 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate that the pharmacodynamic (PD) effect of injections of 1000 mg efgartigimod PH20 SC (efgartigimod coformulated with recombinant human hyaluronidase PH20 for subcutaneous administration), administered once weekly for 4 administrations, is NI (noninferior) to IV infusions of efgartigimod (efgartigimod formulation for intravenous infusion) at a dose of 10 mg/kg administered once weekly for 4 administrations. Secondary objectives: To compare the PD effect of efgartigimod PH20 SC and efgartigimod IV over time To evaluate the pharmacokinetics (PK) of efgartigimod PH20 SC and efgartigimod IV To evaluate the safety, tolerability, and immunogenicity of efgartigimod PH20 SC and efgartigimod IV To evaluate the clinical efficacy of efgartigimod PH20 SC and efgartigimod IV
    Protection of trial subjects
    This study was conducted according to ICH GCP, the principles of the Declaration of Helsinki, and other applicable local ethical and legal requirements. The participant’s informed consent was documented by the dated signature of the participant (and/or assent, if applicable) and the dated signature of the investigator or investigator’s delegate. Evaluation of eligibility was performed at screening and confirmed at visit 1.
    Background therapy
    		 Efgartigimod was administered concomitantly with a stable dose of the participant’s current gMG therapy, which could have included AChE (acetylcholinesterase) inhibitors, steroids, and NSIDs (nonsteroidal immunosuppressive drugs). At the end of the study, eligible participants could roll over to ARGX-113-2002 to receive efgartigimod PH20 SC. This is the open label long term safety extension study.
    Evidence for comparator
    		 Open label parallel-group, non-inferiority study
    Actual start date of recruitment
    05 Feb 2021
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 1 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 4
    Country: Number of subjects enrolled
    Poland: 36
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    Hungary: 5
    Country: Number of subjects enrolled
    Italy: 6
    Country: Number of subjects enrolled
    Georgia: 20
    Country: Number of subjects enrolled
    Japan: 8
    Country: Number of subjects enrolled
    Russian Federation: 4
    Country: Number of subjects enrolled
    United States: 19
    Worldwide total number of subjects
    111
    EEA total number of subjects
    60
    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)
    81
    From 65 to 84 years
    30
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Subject’s evaluation of eligibility was performed at screening and confirmed at randomization visit 1. The overall study duration per subject was approximately 12 weeks spanning the study periods - 2 weeks for screening, 3 weeks for treatment, and 7 weeks for follow-up.

    Pre-assignment
    Screening details
    		 153 patients were screened, 111 patients were randomized, 110 patients were treated 1:1 at the day 1 visit to receive efgartigimod PH20 SC 1000 mg or efgartigimod IV 10 mg/kg once weekly for 4 administrations (4 doses on days 1, 8, 15, and 22). One participant was randomized to the efgartigimod IV arm but did not receive efgartigimod due to an AE.

    Period 1
    Period 1 title
    Treatment period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Efgartigimod PH20 SC
    Arm description
    		 Efgartigimod drug product of 180 mg/mL for a fixed dose of 1000 mg for SC injection coformulated with 2000 U/mL rHuPH20 once weekly for 4 administrations (4 doses on days 1, 8, 15, and 22) - Efgartigimod PH20 SC was administered at the site by the study staff or by the participant (or their caregiver, as appropriate), under supervision of the site staff.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Efgartigimod
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in vial
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1000 mg once weekly for a total of 4 SC injections

    Arm title
    		 Efgartigimod IV
    Arm description
    		 Efgartigimod drug product of 20 mg/mL for dosing of 10 mg/kg for IV infusion once weekly for 4 administrations (4 doses on days 1, 8, 15, and 22) - Efgartigimod IV was administered by a 1-hour infusion performed by the site staff.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Efgartigimod
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    10 mg/kg once weekly for a total of 4 IV infusions

    Number of subjects in period 1 [1]
    		Efgartigimod PH20 SC Efgartigimod IV
    Started
    55
    55
    Completed
    52
    55
    Not completed
    3
    0
         Adverse event, non-fatal
    2
    -
         Other
    1
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 111 participants were enrolled and randomized to receive the investigational medicinal product (IMP): 55 participants in the efgartigimod PH20 SC arm and 56 participants in the efgartigimod IV arm. There were 110 participants (55 in each arm) in the safety analysis set and the intent to treat (ITT) and modified intent-to-treat (mITT) analysis sets.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Efgartigimod PH20 SC
    Reporting group description
    		 Efgartigimod drug product of 180 mg/mL for a fixed dose of 1000 mg for SC injection coformulated with 2000 U/mL rHuPH20 once weekly for 4 administrations (4 doses on days 1, 8, 15, and 22) - Efgartigimod PH20 SC was administered at the site by the study staff or by the participant (or their caregiver, as appropriate), under supervision of the site staff.

    Reporting group title
    Efgartigimod IV
    Reporting group description
    		 Efgartigimod drug product of 20 mg/mL for dosing of 10 mg/kg for IV infusion once weekly for 4 administrations (4 doses on days 1, 8, 15, and 22) - Efgartigimod IV was administered by a 1-hour infusion performed by the site staff.

    Reporting group values
    		 Efgartigimod PH20 SC Efgartigimod IV Total
    Number of subjects
    		 55 55 110
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 43 37 80
        From 65-84 years
    		 12 18 30
    Age continuous
    Units: years
        median (full range (min-max))
    		 53.0 (19 to 84) 59.0 (24 to 83) -
    Gender categorical
    Units: Subjects
        Female
    		 31 34 65
        Male
    		 24 21 45
    Subject analysis sets

    Subject analysis set title
    ITT analysis set
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized participants who were exposed to the IMP.

    Subject analysis set title
    mITT analysis set
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    All randomized participants with a value for total IgG levels at baseline and at least 1 postbaseline time point.

    Subject analysis set title
    Safety analysis set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomized participants who were exposed to IMP.

    Subject analysis set title
    PK analysis set
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    A subset of the safety analysis set with at least 1 post dose PK measurement.

    Subject analysis sets values
    		 ITT analysis set mITT analysis set Safety analysis set PK analysis set
    Number of subjects
    110
    110
    110
    98
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    80
    80
    80
        From 65-84 years
    30
    30
    30
    Age continuous
    Units: years
        median (full range (min-max))
    53.5 (19 to 84)
    53.5 (19 to 84)
    53.5 (19 to 84)
    Gender categorical
    Units: Subjects
        Female
    65
    65
    65
        Male
    45
    45
    45

    End points

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    End points reporting groups
    Reporting group title
    Efgartigimod PH20 SC
    Reporting group description
    		 Efgartigimod drug product of 180 mg/mL for a fixed dose of 1000 mg for SC injection coformulated with 2000 U/mL rHuPH20 once weekly for 4 administrations (4 doses on days 1, 8, 15, and 22) - Efgartigimod PH20 SC was administered at the site by the study staff or by the participant (or their caregiver, as appropriate), under supervision of the site staff.

    Reporting group title
    Efgartigimod IV
    Reporting group description
    		 Efgartigimod drug product of 20 mg/mL for dosing of 10 mg/kg for IV infusion once weekly for 4 administrations (4 doses on days 1, 8, 15, and 22) - Efgartigimod IV was administered by a 1-hour infusion performed by the site staff.

    Subject analysis set title
    ITT analysis set
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized participants who were exposed to the IMP.

    Subject analysis set title
    mITT analysis set
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    All randomized participants with a value for total IgG levels at baseline and at least 1 postbaseline time point.

    Subject analysis set title
    Safety analysis set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All randomized participants who were exposed to IMP.

    Subject analysis set title
    PK analysis set
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    A subset of the safety analysis set with at least 1 post dose PK measurement.

    Primary: Percent reduction from baseline in total IgG levels at day 29 (mITT Analysis set)

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    End point title
    		 Percent reduction from baseline in total IgG levels at day 29 (mITT Analysis set)
    End point description
    ANCOVA Analysis of Percent Change From Baseline in Total IgG Level at Day 29 (ie, 7 days after the fourth IV or SC administration). The results were consistent when the ANCOVA analysis was repeated for the per-protocol analysis set and for the AChR-Ab seropositive population in the mITT analysis set.
    End point type
    Primary
    End point timeframe
    From week 0 to week 4
    End point values
    		 Efgartigimod PH20 SC Efgartigimod IV
    Number of subjects analysed
    50
    52
    Units: percent
    least squares mean (confidence interval 95%)
        mITT
    -66.4 (-68.91 to -63.86)
    -62.2 (-64.67 to -59.72)
    Statistical analysis title
    		 Statistical Analysis Plan - EFG PH20 SC vs EFG IV
    Statistical analysis description
    The primary endpoint was analyzed using an ANCOVA model with treatment as a factor and total IgG levels at baseline as a covariate. The NI evaluation was based on a percent reduction from baseline in total IgG levels at day 29 (week 4) using an NI margin of 10%. Only the results for mITT analysis set are entered. The results were consistent when the ANCOVA analysis was repeated for the per-protocol analysis set and for the AChR-Ab seropositive population in the mITT analysis set.
    Comparison groups
    Efgartigimod PH20 SC v Efgartigimod IV
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -4.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.73
         upper limit
    		 -0.66
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.782

    Secondary: Percent reduction from baseline in total IgG levels over time (mITT Analysis Set)

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    End point title
    		 Percent reduction from baseline in total IgG levels over time (mITT Analysis Set)
    End point description
    Total IgG level percent change from baseline over time for the overall population.
    End point type
    Secondary
    End point timeframe
    From baseline to week 10
    End point values
    		 Efgartigimod PH20 SC Efgartigimod IV
    Number of subjects analysed
    55
    55
    Units: percent
    arithmetic mean (standard error)
        Week 1
    -40.1 ( 1.45 )
    -39.6 ( 1.51 )
        Week 2
    -56.9 ( 1.57 )
    -55.1 ( 1.85 )
        Week 3
    -62.2 ( 1.41 )
    -59 ( 2 )
        Week 4
    -64.7 ( 1.95 )
    -62.3 ( 1.24 )
        Week 5
    -57.4 ( 1.7 )
    -49.9 ( 2.17 )
        Week 6
    -44 ( 2.52 )
    -38.9 ( 2.24 )
        Week 7
    -31.2 ( 4.67 )
    -25.3 ( 2.78 )
        Week 8
    -8.9 ( 8.65 )
    -14.6 ( 3.13 )
        Week 10
    7.8 ( 7.78 )
    -3.1 ( 3.82 )
    No statistical analyses for this end point

    Secondary: Absolute values, change from baseline and percent reduction from baseline in AChR-Ab levels over time in AChR- Ab positive patients (mITT Analysis Set)

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    End point title
    		 Absolute values, change from baseline and percent reduction from baseline in AChR-Ab levels over time in AChR- Ab positive patients (mITT Analysis Set)
    End point description
    Absolute values, change from baseline and percent reduction from baseline in AChR-Ab levels over time in AChR-Ab positive patients measured in mITT Analysis Set. Descriptive statistics have been used for this secondary end point.
    End point type
    Secondary
    End point timeframe
    From baseline to week 10
    End point values
    		 Efgartigimod PH20 SC Efgartigimod IV
    Number of subjects analysed
    45
    46
    Units: percent
    arithmetic mean (standard error)
        Week 1
    -42.5 ( 1.5 )
    -43.7 ( 1.55 )
        Week 2
    -57.4 ( 1.39 )
    -55.1 ( 1.52 )
        Week 3
    -61.8 ( 1.6 )
    -59.2 ( 1.66 )
        Week 4
    -62.2 ( 1.76 )
    -59.6 ( 1.74 )
        Week 5
    -55.3 ( 1.52 )
    -47.2 ( 2.98 )
        Week 6
    -40.4 ( 3.13 )
    -29.9 ( 4.61 )
        Week 7
    -26.7 ( 4.76 )
    -15.8 ( 5.63 )
        Week 8
    -14.5 ( 7.82 )
    -7.1 ( 6.02 )
        Week 10
    13.5 ( 23.16 )
    10.3 ( 7.85 )
    No statistical analyses for this end point

    Secondary: Absolute values, change from baseline, and percent reduction from baseline in IgG subtype levels over time (mITT Analysis Set)

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    End point title
    		 Absolute values, change from baseline, and percent reduction from baseline in IgG subtype levels over time (mITT Analysis Set)
    End point description
    Median (IQR) Percent Change From Baseline and AUEC for the Percent Change From Baseline for the IgG Subtypes (IgG1, IgG2, IgG3, and IgG4) in the Overall Population. The highest number of patients among all weeks for the analysis is chosen for each arm. Descriptive statistics have been used for this secondary end point.
    End point type
    Secondary
    End point timeframe
    Baseline to week 10
    End point values
    		 Efgartigimod PH20 SC Efgartigimod IV
    Number of subjects analysed
    55
    55
    Units: percent x days
    median (inter-quartile range (Q1-Q3))
        Percent change from baseline at week 4 IgG1
    -71 (-79.3 to -56.6)
    -68.4 (-73 to -61.5)
        Percent change from baseline at week 4 IgG2
    -65.6 (-72.2 to -58.1)
    -64.5 (-73 to -57.4)
        Percent change from baseline at week 4 IgG3
    -69.6 (-78.3 to -58.4)
    -64.7 (-76.9 to -59.5)
        Percent change from baseline at week 4 IgG4
    -56.4 (-64.4 to -37.2)
    -55.5 (-64.2 to -42.1)
        AUEC percent change from baseline to week 10 IgG1
    -3054.1 (-3679.2 to -1933.1)
    -2935.2 (-3195.0 to -2422.0)
        AUEC percent change from baseline to week 10 IgG2
    -2709.9 (-3551.5 to -1932.2)
    -2796.3 (-3187.9 to -2076.3)
        AUEC percent change from baseline to week 10 IgG3
    -2732.9 (-3437.9 to -1602.7)
    -2566.5 (-3567.4 to -1973.9)
        AUEC percent change from baseline to week 10 IgG4
    -2060.5 (-2815.7 to -874.3)
    -1979.4 (-2730.6 to -1160.1)
    No statistical analyses for this end point

    Secondary: AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set)

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    End point title
    		 AUEC of the Percent Change From Baseline in Total IgG Level (mITT Analysis Set)
    End point description
    AUEC of the percent reduction from baseline total IgG per dosing interval (days 1-8, days 8-15, days 15-22, and days 22-29), days 1-29, days 1-57 and over the entire study (days 1-71). The highest number of patients among all weeks for the analysis is chosen for each arm. Descriptive statistics have been used for this secondary end point.
    End point type
    Secondary
    End point timeframe
    From baseline to week 10
    End point values
    		 Efgartigimod PH20 SC Efgartigimod IV
    Number of subjects analysed
    55
    55
    Units: percent days
    arithmetic mean (standard error)
        Days 1-8 (baseline-week 1)
    -138.9 ( 5.48 )
    -139.1 ( 5.67 )
        Days 8-15 (week 1-week 2)
    -341.9 ( 9.9 )
    -328.3 ( 10.98 )
        Days 15-22 (week 2-week 3)
    -416.0 ( 12.06 )
    -399.8 ( 14.46 )
        Days 22-29 (week 3-week 4)
    -447.3 ( 9.24 )
    -427.0 ( 9.76 )
        Days 1-29 (baseline-week 4)
    -1332.5 ( 30.78 )
    -1311.6 ( 26.35 )
        Days 1-57 (baseline-week 8)
    -2515.9 ( 96.98 )
    -2387.6 ( 77.61 )
        Days 1-71 (baseline-week 10)
    -2562.9 ( 171.86 )
    -2500.3 ( 116.10 )
    No statistical analyses for this end point

    Secondary: Еfgartigimod IV and PH20 SC serum pharmacokinetic parameter Ctrough

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    End point title
    		 Еfgartigimod IV and PH20 SC serum pharmacokinetic parameter Ctrough
    End point description
    Evaluation of observed predose concentration (Ctrough) (after all doses for the IV and SC treatment arms). The analysis will present data from Week 1 to Week 4. Descriptive statistics have been used for this secondary end point.
    End point type
    Secondary
    End point timeframe
    From Week 1 to Week 4.
    End point values
    		 Efgartigimod PH20 SC Efgartigimod IV
    Number of subjects analysed
    49
    51
    Units: μg/mL
    arithmetic mean (standard deviation)
        Ctrough week 1
    18.3 ( 8.05 )
    16.4 ( 33.0 )
        Ctrough week 2
    21.4 ( 8.36 )
    14.0 ( 6.92 )
        Ctrough week 3
    22.5 ( 9.61 )
    15.2 ( 8.05 )
        Ctrough week 4
    22.0 ( 8.12 )
    14.9 ( 6.43 )
    No statistical analyses for this end point

    Secondary: Efgartigimod IV serum pharmacokinetic parameter Cmax

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    End point title
    		 Efgartigimod IV serum pharmacokinetic parameter Cmax [1]
    End point description
    Evaluation of maximum observed concentration (Cmax) (after all doses for the IV treatment arm). The analysis will present data from Baseline to Week 3. Descriptive statistics have been used for this secondary end point.
    End point type
    Secondary
    End point timeframe
    From Baseline to week 3
    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: Descriptive statistics have been performed for this secondary endpoint.
    End point values
    		 Efgartigimod IV
    Number of subjects analysed
    54
    Units: μg/mL
    arithmetic mean (standard deviation)
        Cmax Baseline
    199 ( 62.8 )
        Cmax week 1
    215 ( 63.0 )
        Cmax week 2
    211 ( 75.0 )
        Cmax week 3
    206 ( 59.5 )
    No statistical analyses for this end point

    Secondary: Incidence and prevalence of ADA against Efgartigimod (Safety Analysis Set)

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    End point title
    		 Incidence and prevalence of ADA against Efgartigimod (Safety Analysis Set)
    End point description
    Classification, incidence, and prevalence of antidrug antibodies (ADA) against Efgartigimod in the overall population. Descriptive statistics have been used for this secondary end point.
    End point type
    Secondary
    End point timeframe
    From baseline to week 10
    End point values
    		 Efgartigimod PH20 SC Efgartigimod IV
    Number of subjects analysed
    55
    55
    Units: percent
    number (not applicable)
        Baseline ADA positive sample
    12.7
    9.1
        Baseline ADA negative sample
    87.3
    90.9
        ADA+ treatment boosted (prs classif)
    1.8
    1.8
        ADA+ treatment induced (prs classif)
    32.7
    18.2
        ADA- treatment unaffected (prs classif)
    10.9
    7.3
        ADA- (prs classif)
    54.5
    72.7
        ADA incidence
    34.5
    20.0
        ADA prevalence
    45.5
    27.3
    No statistical analyses for this end point

    Secondary: Incidence and prevalence of antibodies against rHuPH20 in the SC treatment arm (Safety Analysis Set)

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    End point title
    		 Incidence and prevalence of antibodies against rHuPH20 in the SC treatment arm (Safety Analysis Set) [2]
    End point description
    Participant classification, incidence, and prevalence of antibodies against rHuPH20 in the Efgartigimod PH20 SC Arm. Descriptive statistics have been used for this secondary end point.
    End point type
    Secondary
    End point timeframe
    From baseline to week 10
    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: The endpoint is not applicable to the EFG IV arm.
    End point values
    		 Efgartigimod PH20 SC
    Number of subjects analysed
    55
    Units: percent
    number (not applicable)
        Baseline rHuPH20 Ab - sample
    89.1
        Baseline rHuPH20 Ab + sample
    10.9
        rHuPH20 Ab - (prs classif)
    85.5
        Treatment-unaffected rHuPH20 Ab - (prs classif)
    9.1
        Treatment-induced rHuPH20 Ab + (prs classif)
    3.6
        Treatment-boosted rHuPH20 Ab + (prs classif)
    1.8
        rHuPH20 antibody incidence
    5.5
        rHuPH20 antibody prevalence
    14.5
    No statistical analyses for this end point

    Secondary: Incidence and severity of AEs and SAEs (Safety Analysis Set)

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    End point title
    		 Incidence and severity of AEs and SAEs (Safety Analysis Set)
    End point description
    Evaluation of incidence and severity of treatment-emergent adverse events (TEAEs) and incidence of serious AEs (SAEs). Descriptive statistics have been used for this secondary end point.
    End point type
    Secondary
    End point timeframe
    From baseline to week 10
    End point values
    		 Efgartigimod PH20 SC Efgartigimod IV
    Number of subjects analysed
    55
    55
    Units: percent
    number (not applicable)
        ≥1 AE
    67.3
    50.9
        ≥1 SAE
    14.5
    7.3
        ≥1 Grade 3 or higher AE
    16.4
    7.3
        ≥1 AESI
    18.2
    16.4
        ≥1 Injection site reaction (localized)
    38.2
    1.8
        ≥1 Infusion- or injection-related reaction
    25.5
    3.6
        ≥1 Fatal AE
    0
    0
        ≥1 Treatment-related AE according to PI
    43.6
    21.8
        ≥1 Procedure-related AE according to PI
    25.5
    3.6
        ≥1 Treatment-related SAE
    0
    0
        ≥1 AE for which the IMP was interrupted
    1.8
    0
        ≥1 AE for which the IMP was discontinued
    3.6
    0
    No statistical analyses for this end point

    Secondary: MG-ADL Responders (ITT Analysis Set)

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    End point title
    		 MG-ADL Responders (ITT Analysis Set)
    End point description
    Evaluation of number and percentage of Myasthenia Gravis Activities of Daily Living (MG-ADL) responders in the overall population (ITT Analysis Set). Descriptive statistics have been used for this secondary end point.
    End point type
    Secondary
    End point timeframe
    From baseline to week 10
    End point values
    		 Efgartigimod PH20 SC Efgartigimod IV
    Number of subjects analysed
    55
    55
    Units: percent
    number (not applicable)
        Overall
    69.1
    69.1
    No statistical analyses for this end point

    Secondary: QMG Responders (ITT Analysis Set)

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    End point title
    		 QMG Responders (ITT Analysis Set)
    End point description
    Evaluation of number and percentage of Quantitative Myasthenia Gravis (QMG) responders in the overall population (ITT Analysis Set). Descriptive statistics have been used for this secondary end point. One subject in the EFG IV arm had no post-baseline QMG assessment and thus was excluded from the denominator.
    End point type
    Secondary
    End point timeframe
    From baseline to week 10
    End point values
    		 Efgartigimod PH20 SC Efgartigimod IV
    Number of subjects analysed
    55
    54
    Units: percent
    number (not applicable)
        Overall
    65.5
    51.9
    No statistical analyses for this end point

    Secondary: Change from baseline in MG-ADL total score over time (ITT Analysis Set)

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    End point title
    		 Change from baseline in MG-ADL total score over time (ITT Analysis Set)
    End point description
    Evaluation of MG-ADL Total Score Change from baseline over time for the overall population (ITT Analysis Set). Descriptive statistics have been used for this secondary end point.
    End point type
    Secondary
    End point timeframe
    From baseline to week 10
    End point values
    		 Efgartigimod PH20 SC Efgartigimod IV
    Number of subjects analysed
    55
    55
    Units: Total score
    arithmetic mean (standard error)
        Week 1
    -2.2 ( 0.33 )
    -2.0 ( 0.30 )
        Week 2
    -3.6 ( 0.40 )
    -3.2 ( 0.35 )
        Week 3
    -4.7 ( 0.36 )
    -4.3 ( 0.33 )
        Week 4
    -5.1 ( 0.38 )
    -4.7 ( 0.37 )
        Week 5
    -4.9 ( 0.36 )
    -4.3 ( 0.41 )
        Week 6
    -4.2 ( 0.35 )
    -3.7 ( 0.44 )
        Week 7
    -3.9 ( 0.35 )
    -3.6 ( 0.44 )
        Week 8
    -3.3 ( 0.34 )
    -2.9 ( 0.4 )
        Week 10
    -2.2 ( 0.44 )
    -2.1 ( 0.43 )
    No statistical analyses for this end point

    Secondary: Change from baseline in QMG score over time (ITT Analysis Set)

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    End point title
    		 Change from baseline in QMG score over time (ITT Analysis Set)
    End point description
    Evaluation of QMG Total Score change from baseline over time for the overall population (ITT Analysis Set). Descriptive statistics have been used for this secondary end point.
    End point type
    Secondary
    End point timeframe
    From baseline to week 10
    End point values
    		 Efgartigimod PH20 SC Efgartigimod IV
    Number of subjects analysed
    55
    55
    Units: Total score
    arithmetic mean (standard error)
        Week 1
    -3 ( 0.48 )
    -2 ( 0.44 )
        Week 2
    -4.3 ( 0.58 )
    -3.4 ( 0.44 )
        Week 3
    -5.7 ( 0.61 )
    -4.5 ( 0.5 )
        Week 4
    -6.1 ( 0.62 )
    -5.2 ( 0.52 )
        Week 5
    -5.9 ( 0.61 )
    -5 ( 0.57 )
        Week 6
    -5.2 ( 0.6 )
    -5 ( 0.61 )
        Week 7
    -3.9 ( 0.61 )
    -4.1 ( 0.55 )
        Week 8
    -3.7 ( 0.66 )
    -3.3 ( 0.53 )
        Week 10
    -2.3 ( 0.6 )
    -2.8 ( 0.53 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Throughout the treatment period.
    Adverse event reporting additional description
    Both efgartigimod PH20 SC and IV were well tolerated and had a favorable safety profile in participants with gMG, with most AE being mild to moderate in severity. No deaths or grade 4 AE occurred during the study period. 11.8% of patients had Grade 3 AE reported. The frequency of AE leading to treatment interruption and discontinuation was low.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Efgartigimod PH20 SC
    Reporting group description
    		 Efgartigimod drug product of 180 mg/mL for a fixed dose of 1000 mg for SC injection coformulated with 2000 U/mL rHuPH20 once weekly for 4 administrations (4 doses on days 1, 8, 15, and 22) - Efgartigimod PH20 SC was administered at the site by the study staff or by the participant (or their caregiver, as appropriate), under supervision of the site staff.

    Reporting group title
    Efgartigimod IV
    Reporting group description
    		 Efgartigimod drug product of 20 mg/mL for dosing of 10 mg/kg for IV infusion once weekly for 4 administrations (4 doses on days 1, 8, 15, and 22) - Efgartigimod IV was administered by a 1-hour infusion performed by the site staff.

    Serious adverse events
    		 Efgartigimod PH20 SC Efgartigimod IV
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 55 (14.55%)
    4 / 55 (7.27%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Humerus fracture
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 55 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure congestive
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 55 (1.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Myasthenia gravis
         subjects affected / exposed
    5 / 55 (9.09%)
    1 / 55 (1.82%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Optic neuritis
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 55 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 55 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 55 (1.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Testicular cyst
         subjects affected / exposed
    0 / 55 (0.00%)
    1 / 55 (1.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 55 (1.82%)
    1 / 55 (1.82%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    1 / 55 (1.82%)
    0 / 55 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Efgartigimod PH20 SC Efgartigimod IV
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    37 / 55 (67.27%)
    23 / 55 (41.82%)
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 55 (0.00%)
    3 / 55 (5.45%)
         occurrences all number
    0
    3
    Fall
         subjects affected / exposed
    1 / 55 (1.82%)
    3 / 55 (5.45%)
         occurrences all number
    1
    3
    Nervous system disorders
    Headache
         subjects affected / exposed
    7 / 55 (12.73%)
    7 / 55 (12.73%)
         occurrences all number
    10
    11
    Myasthenia gravis
         subjects affected / exposed
    6 / 55 (10.91%)
    1 / 55 (1.82%)
         occurrences all number
    8
    2
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 55 (3.64%)
    3 / 55 (5.45%)
         occurrences all number
    2
    3
    Injection site bruising
         subjects affected / exposed
    4 / 55 (7.27%)
    0 / 55 (0.00%)
         occurrences all number
    4
    0
    Injection site erythema
         subjects affected / exposed
    7 / 55 (12.73%)
    0 / 55 (0.00%)
         occurrences all number
    7
    0
    Injection site pain
         subjects affected / exposed
    3 / 55 (5.45%)
    0 / 55 (0.00%)
         occurrences all number
    3
    0
    Injection site pruritus
         subjects affected / exposed
    5 / 55 (9.09%)
    0 / 55 (0.00%)
         occurrences all number
    5
    0
    Injection site rash
         subjects affected / exposed
    8 / 55 (14.55%)
    0 / 55 (0.00%)
         occurrences all number
    14
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 55 (1.82%)
    3 / 55 (5.45%)
         occurrences all number
    5
    3
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    1 / 55 (1.82%)
    3 / 55 (5.45%)
         occurrences all number
    1
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Jul 2021
    • Increased sample size from 76 to 110 to quantify the clinical safety and efficacy profile of the efgartigimod PH20 SC formulation • Defined IVIg and immunoglobulin administered SC as rescue medication • Removed “suspected transmission of any infectious agent” as an SAE • Updated the potential risk to the teratogenicity/fetotoxicity mitigation strategy

    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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