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    Clinical Trial Results:
    A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study Investigating the Safety of Ritlecitinib (PF-06651600) in Adult Participants With Alopecia Areata

    Summary
    EudraCT number
    		 2020-001509-21
    Trial protocol
    		 PL  
    Global end of trial date

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Nov 2022
    First version publication date
    02 Nov 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    B7981037
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04517864
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Interim
    Date of interim/final analysis
    11 May 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 Jan 2022
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    This was a Phase 2a, randomized, double-blind, parallel group, placebo-controlled safety study designed to evaluate the safety and tolerability of ritlecitinib, including the assessments of brainstem auditory evoked potential (BAEP) and intraepidermal nerve fiber (IENF), in adults 18 to ≤50 years of age with ≥25% scalp hair loss due to alopecia areata (AA).
    Protection of trial subjects
    This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of subjects.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Sep 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 2
    Country: Number of subjects enrolled
    Canada: 8
    Country: Number of subjects enrolled
    Poland: 36
    Country: Number of subjects enrolled
    United States: 25
    Worldwide total number of subjects
    71
    EEA total number of subjects
    36
    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)
    71
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 71 subjects were enrolled and randomized to double-blind treatment and treated (36 in the Ritlecitinib 200/50 mg once daily [QD] arm and 35 in the Placebo -> Ritlecitinib 200/50 mg QD arm).

    Pre-assignment
    Screening details
    		 A total of 131 subjects were screened for this study, among whom 71 subjects were randomized to double-blind treatment with 53 screen failures and 7 subjects were not screen failure but not randomized.

    Period 1
    Period 1 title
    Placebo-Controlled Phase
    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
    		 Ritlecitinib 200/50 mg QD
    Arm description
    		 In the 9-month Placebo-Controlled Phase, each subject received ritlecitinib 200 mg QD (50 mg/tablet ×4) during the initial 4-week period, and received 1 tablet of ritlecitinib 50 mg QD during the remainder of this treatment phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ritlecitinib
    Investigational medicinal product code
    PF-06651600
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ritlecitinib 200 mg QD (50 mg/tablet ×4) was received during the initial 4-week period, and 1 tablet of ritlecitinib 50 mg QD was received during the remainder of the Placebo-Controlled Phase.

    Arm title
    		 Placebo -> Ritlecitinib 200/50 mg QD
    Arm description
    		 In the 9-month Placebo-Controlled Phase, each subject received a total of 4 tablets of placebo QD during the initial 4-week period, and received 1 tablet of placebo QD during the remainder of this treatment phase.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    A total of 4 tablets of Placebo QD were received during the initial 4-week period, and 1 tablet of Placebo QD was received during the remainder of the Placebo-Controlled Phase.

    Number of subjects in period 1
    		Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Started
    36
    35
    Completed
    32
    33
    Not completed
    4
    2
         Consent withdrawn by subject
    1
    1
         Adverse event, non-fatal
    1
    -
         Lost to follow-up
    1
    1
         Protocol deviation
    1
    -
    Period 2
    Period 2 title
    Active Therapy Extension Phase
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ritlecitinib 200/50 mg QD
    Arm description
    		 In the 15-month Active Therapy Extension Phase, each subject received 1 tablet of ritlecitinib 50 mg QD and 3 tablets of placebo QD during the initial 4-week period, and then received 1 tablet of Ritlecitinib 50 mg QD during the remainder of this treatment phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ritlecitinib
    Investigational medicinal product code
    PF-06651600
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One tablet of ritlecitinib 50 mg QD and 3 tablets of placebo QD were received during the initial 4-week period, and 1 tablet of ritlecitinib 50 mg QD was received during the remainder of the Active Therapy Extension Phase.

    Arm title
    		 Placebo -> Ritlecitinib 200/50 mg QD
    Arm description
    		 In the 15-month Active Therapy Extension Phase, each subject received ritlecitinib 200 mg QD (50 mg/tablet ×4) during the initial 4-week period, and then received 1 tablet of ritlecitinib 50 mg QD during the remainder of this treatment phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ritlecitinib
    Investigational medicinal product code
    PF-06651600
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ritlecitinib 200 mg QD (50 mg/tablet ×4) was received during the initial 4-week period, and 1 tablet of ritlecitinib 50 mg QD was received during the remainder of the Active Therapy Extension Phase.

    Number of subjects in period 2 [1]
    		Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Started
    32
    31
    Completed
    31
    33
    Not completed
    1
    0
         Adverse event, non-fatal
    1
    -
    Joined
    0
    2
         Not yet entered at the time of the PCD data-cut
    -
    2
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: The number is correct as provided

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Ritlecitinib 200/50 mg QD
    Reporting group description
    		 In the 9-month Placebo-Controlled Phase, each subject received ritlecitinib 200 mg QD (50 mg/tablet ×4) during the initial 4-week period, and received 1 tablet of ritlecitinib 50 mg QD during the remainder of this treatment phase.

    Reporting group title
    Placebo -> Ritlecitinib 200/50 mg QD
    Reporting group description
    		 In the 9-month Placebo-Controlled Phase, each subject received a total of 4 tablets of placebo QD during the initial 4-week period, and received 1 tablet of placebo QD during the remainder of this treatment phase.

    Reporting group values
    		 Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD Total
    Number of subjects
    		 36 35 71
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 36 35 71
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 35.1 ± 9.64 34.2 ± 8.95 -
    Sex: Female, Male
    Units: Subjects
        Female
    		 25 25 50
        Male
    		 11 10 21
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 3 0 3
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 7 4 11
        White
    		 26 28 54
        More than one race
    		 0 2 2
        Unknown or Not Reported
    		 0 1 1
    Baseline Percentage of Nerve Fibers With Axonal Swelling
    Units: Percentage
        arithmetic mean (standard deviation)
    		 1.8 ± 2.48 1.8 ± 2.07 -
    Baseline Intraepidermal Nerve Fiber Density (IENFD)
    Units: /mm
        arithmetic mean (standard deviation)
    		 10.2 ± 3.81 11.0 ± 3.95 -
    Baseline Severity of Alopecia Tool (SALT) Scores for Non-AT/AU Subjects
    AT=alopecia totalis; AU=alopecia universalis.
    Units: Units on a scale
        arithmetic mean (standard deviation)
    		 59.6 ± 30.31 53.7 ± 24.18 -

    End points

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    End points reporting groups
    Reporting group title
    Ritlecitinib 200/50 mg QD
    Reporting group description
    		 In the 9-month Placebo-Controlled Phase, each subject received ritlecitinib 200 mg QD (50 mg/tablet ×4) during the initial 4-week period, and received 1 tablet of ritlecitinib 50 mg QD during the remainder of this treatment phase.

    Reporting group title
    Placebo -> Ritlecitinib 200/50 mg QD
    Reporting group description
    		 In the 9-month Placebo-Controlled Phase, each subject received a total of 4 tablets of placebo QD during the initial 4-week period, and received 1 tablet of placebo QD during the remainder of this treatment phase.
    Reporting group title
    Ritlecitinib 200/50 mg QD
    Reporting group description
    		 In the 15-month Active Therapy Extension Phase, each subject received 1 tablet of ritlecitinib 50 mg QD and 3 tablets of placebo QD during the initial 4-week period, and then received 1 tablet of Ritlecitinib 50 mg QD during the remainder of this treatment phase.

    Reporting group title
    Placebo -> Ritlecitinib 200/50 mg QD
    Reporting group description
    		 In the 15-month Active Therapy Extension Phase, each subject received ritlecitinib 200 mg QD (50 mg/tablet ×4) during the initial 4-week period, and then received 1 tablet of ritlecitinib 50 mg QD during the remainder of this treatment phase.

    Primary: Change From Baseline in I-V Interwave Latency on Brainstem Auditory Evoked Potentials (BAEP) at a Stimulus Intensity of 80 dB From the Right Side at Month 9

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    End point title
    		 Change From Baseline in I-V Interwave Latency on Brainstem Auditory Evoked Potentials (BAEP) at a Stimulus Intensity of 80 dB From the Right Side at Month 9
    End point description
    BAEP interwave I-V latency was the primary endpoint for this study. High-intensity stimulation (80dB) was used. Subjects had BAEP evaluations performed at the same evaluation center, by the same audiology professional using the same equipment, during the study. Audiology and BAEP evaluations were done on the same day, with audiology assessment first. If they could not be done on the same day, assessments had to be within 7 days of each other. A central reader was used for BAEP to confirm that locally read BAEP waves were labelled appropriately and at their peak so that latency were accurate. Central reading also ensured consistency in BAEP interpretation. Analysis population included all subjects who received at least 1 dose of study intervention. Number of subjects analyzed signifies number of subjects who were evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline, Month 9 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase)
    End point values
    		 Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    31
    32
    Units: Millisecond (ms)
    least squares mean (confidence interval 95%)
        Month 9
    0.011 (-0.043 to 0.065)
    -0.010 (-0.063 to 0.043)
    Statistical analysis title
    		 LS Mean Difference (Ritlecitinib vs Placebo)
    Statistical analysis description
    Linear mixed-effects model with baseline, treatment group, visit (Month 6 and Month 9) and treatment group by visit interaction as fixed effects, and subject as a random effect with an unstructured covariance matrix assumption was used.
    Comparison groups
    Ritlecitinib 200/50 mg QD v Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    0.021
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.056
         upper limit
    		 0.097
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0382

    Primary: Change From Baseline in I-V Interwave Latency on BAEP at a Stimulus Intensity of 80 dB From the Left Side at Month 9

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    End point title
    		 Change From Baseline in I-V Interwave Latency on BAEP at a Stimulus Intensity of 80 dB From the Left Side at Month 9
    End point description
    BAEP interwave I-V latency was the primary endpoint for this study. High-intensity stimulation (80dB) was used. Subjects had BAEP evaluations performed at the same evaluation center, by the same audiology professional using the same equipment, during the study. Audiology and BAEP evaluations were done on the same day, with audiology assessment first. If they could not be done on the same day, assessments had to be within 7 days of each other. A central reader was used for BAEP to confirm that locally read BAEP waves were labelled appropriately and at their peak so that latency were accurate. Central reading also ensured consistency in BAEP interpretation. Analysis population included all subjects who received at least 1 dose of study intervention. Number of subjects analyzed signifies number of subjects who were evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline, Month 9 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase)
    End point values
    		 Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    31
    32
    Units: ms
    least squares mean (confidence interval 95%)
        Month 9
    0.031 (-0.012 to 0.075)
    0.022 (-0.020 to 0.065)
    Statistical analysis title
    		 LS Mean Difference (Ritlecitinib vs Placebo)
    Statistical analysis description
    Linear mixed-effects model with baseline, treatment group, visit (Month 6 and Month 9) and treatment group by visit interaction as fixed effects, and subject as a random effect with an unstructured covariance matrix assumption was used.
    Comparison groups
    Ritlecitinib 200/50 mg QD v Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    0.009
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.052
         upper limit
    		 0.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0307

    Secondary: Change From Baseline in I-V Interwave Latency on BAEP at 80 dB from the Right Side at Month 6

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    End point title
    		 Change From Baseline in I-V Interwave Latency on BAEP at 80 dB from the Right Side at Month 6
    End point description
    High-intensity stimulation (80dB) was used. Subjects had BAEP evaluations performed at the same evaluation center, by the same audiology professional using the same equipment, during the study. Audiology and BAEP evaluations were done on the same day, with audiology assessment first. If they could not be done on the same day, assessments had to be within 7 days of each other. A central reader was used for BAEP to confirm that locally read BAEP waves were labelled appropriately and at their peak so that latency were accurate. Central reading also ensured consistency in BAEP interpretation. Analysis population included all subjects who received at least 1 dose of study intervention. Number of subjects analyzed signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase)
    End point values
    		 Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    34
    34
    Units: ms
    least squares mean (confidence interval 95%)
        Month 6
    -0.030 (-0.072 to 0.011)
    -0.024 (-0.065 to 0.017)
    Statistical analysis title
    		 LS Mean Difference (Ritlecitinib vs Placebo)
    Statistical analysis description
    Linear mixed-effects model with baseline, treatment group, visit (Month 6 and Month 9) and treatment group by visit interaction as fixed effects, and subject as a random effect with an unstructured covariance matrix assumption was used.
    Comparison groups
    Ritlecitinib 200/50 mg QD v Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    -0.006
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.065
         upper limit
    		 0.053
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0297

    Secondary: Change From Baseline in I-V Interwave Latency on BAEP at 80 dB from the Left Side at Month 6

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    End point title
    		 Change From Baseline in I-V Interwave Latency on BAEP at 80 dB from the Left Side at Month 6
    End point description
    High-intensity stimulation (80dB) was used. Subjects had BAEP evaluations performed at the same evaluation center, by the same audiology professional using the same equipment, during the study. Audiology and BAEP evaluations were done on the same day, with audiology assessment first. If they could not be done on the same day, assessments had to be within 7 days of each other. A central reader was used for BAEP to confirm that locally read BAEP waves were labelled appropriately and at their peak so that latency were accurate. Central reading also ensured consistency in BAEP interpretation. Analysis population included all subjects who received at least 1 dose of study intervention. Number of subjects analyzed signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase)
    End point values
    		 Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    34
    34
    Units: ms
    least squares mean (confidence interval 95%)
        Month 6
    0.021 (-0.011 to 0.054)
    -0.020 (-0.053 to 0.012)
    Statistical analysis title
    		 LS Mean Difference (Ritlecitinib vs Placebo)
    Statistical analysis description
    Linear mixed-effects model with baseline, treatment group, visit (Month 6 and Month 9) and treatment group by visit interaction as fixed effects, and participant as a random effect with an unstructured covariance matrix assumption was used.
    Comparison groups
    Ritlecitinib 200/50 mg QD v Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    0.042
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.005
         upper limit
    		 0.088
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0235

    Secondary: Change From Baseline in Percentage of Intra-epidermal Nerve Fiber (IENF) With Axonal Swelling in Skin Punch Biopsies at Month 9

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    End point title
    		 Change From Baseline in Percentage of Intra-epidermal Nerve Fiber (IENF) With Axonal Swelling in Skin Punch Biopsies at Month 9
    End point description
    The endpoint “axonal dystrophy” referred to the percentage of IENF with axonal swellings. Axonal swellings were evaluated in peripheral skin punch biopsies from the distal part of lower extremities. Axonal swellings were counted by axon. Any IENF with single or multiple swellings was counted as a single event, ie, a single axon with axonal swellings. For each subject, data were reported as the percentage of IENF with any number of swellings. IENF was assessed at Day 1 and Month 9. Subjects who had entered the Active Therapy Extension Phase at Month 6 had a skin punch biopsy taken at Month 6 for IENF assessments instead of at Month 9. The skin biopsy must have been collected before the start of Active Therapy Extension Phase. Analysis population included all subjects who received at least 1 dose of study intervention. Number of subjects analyzed signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 9 (Month 6 for the 2 subjects who entered the Active Therapy Extension Phase at Month 6). Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase.
    End point values
    		 Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    32
    33
    Units: Percentage of Nerve Fibers
    median (inter-quartile range (Q1-Q3))
        End of Placebo-controlled Phase (EOP)
    0.0 (-0.5 to 2.5)
    0.0 (-2.0 to 1.0)
    No statistical analyses for this end point

    Secondary: Change From Baseline in Intraepidermal Nerve Fiber Density (IENFD) in Skin Punch Biopsies at Month 9

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    End point title
    		 Change From Baseline in Intraepidermal Nerve Fiber Density (IENFD) in Skin Punch Biopsies at Month 9
    End point description
    IENFD was evaluated in peripheral skin punch biopsies from the distal part of lower extremities. IENFD was measured by counting the number of fibers and fiber branches that independently crossed the dermal-epidermal barrier (basement membrane). Secondary branching was excluded from quantification and fragments were not counted. The length of the histology section was measured (mm) and the linear epidermal nerve fiber density was reported as number of intraepidermal nerve fibers/mm. Analysis population included all subjects who received at least 1 dose of study intervention. Number of subjects analyzed signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 9 (Month 6 for the 2 subjects who entered the Active Therapy Extension Phase at Month 6). Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase.
    End point values
    		 Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    32
    33
    Units: fibers/mm
    arithmetic mean (standard deviation)
        End of Placebo-controlled Phase (EOP)
    -0.4 ± 3.90
    -0.2 ± 2.72
    No statistical analyses for this end point

    Secondary: Change From Baseline in Amplitude of Wave V on BAEP at a Stimulus Intensity of 80 dB From the Right Side at Month 6 and Month 9

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    End point title
    		 Change From Baseline in Amplitude of Wave V on BAEP at a Stimulus Intensity of 80 dB From the Right Side at Month 6 and Month 9
    End point description
    High-intensity stimulation (80dB) was used. Subjects had BAEP evaluations performed at the same evaluation center, by the same audiology professional using the same equipment, during the study. Audiology and BAEP evaluations were done on the same day, with audiology assessment first. If they could not be done on the same day, assessments had to be within 7 days of each other. A central reader was used for BAEP to confirm that locally read BAEP waves were labelled appropriately and at their peak so that amplitude data were accurate. Central reading also ensured consistency in BAEP interpretation. Analysis population included all subjects who received at least 1 dose of study intervention. Number of subjects analyzed signifies number of subjects who were evaluable for this endpoint. n = x, y in the following table represents the number of evaluable subjects in the Ritlecitinib 200/50 mg QD and Placebo arms, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6 and Month 9 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase)
    End point values
    		 Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    34
    34
    Units: Microvolts (μV)
    least squares mean (confidence interval 95%)
        Month 6 (n = 34, 34)
    -0.031 (-0.063 to 0)
    -0.017 (-0.048 to 0.015)
        Month 9 (n = 31, 32)
    -0.051 (-0.085 to -0.018)
    0.008 (-0.025 to 0.041)
    Statistical analysis title
    		 LS Mean Difference (Ritlecitinib vs Placebo)
    Statistical analysis description
    Month 9
    Comparison groups
    Ritlecitinib 200/50 mg QD v Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    -0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.107
         upper limit
    		 -0.012
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0236
    Notes
    [1] - Linear mixed-effects model with baseline, treatment group, visit (Month 6 and Month 9) and treatment group by visit interaction as fixed effects, and subject as a random effect with an unstructured covariance matrix assumption was used.
    Statistical analysis title
    		 LS Mean Difference (Ritlecitinib vs Placebo)
    Statistical analysis description
    Month 6
    Comparison groups
    Ritlecitinib 200/50 mg QD v Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    -0.015
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.059
         upper limit
    		 0.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0224
    Notes
    [2] - Linear mixed-effects model with baseline, treatment group, visit (Month 6 and Month 9) and treatment group by visit interaction as fixed effects, and subject as a random effect with an unstructured covariance matrix assumption was used.

    Secondary: Change From Baseline in Amplitude of Wave V on BAEP at a Stimulus Intensity of 80 dB From the Left Side at Month 6 and Month 9

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    End point title
    		 Change From Baseline in Amplitude of Wave V on BAEP at a Stimulus Intensity of 80 dB From the Left Side at Month 6 and Month 9
    End point description
    High-intensity stimulation (80dB) was used. Subjects had BAEP evaluations performed at the same evaluation center, by the same audiology professional using the same equipment, during the study. Audiology and BAEP evaluations were done on the same day, with audiology assessment first. If they could not be done on the same day, assessments had to be within 7 days of each other. A central reader was used for BAEP to confirm that locally read BAEP waves were labelled appropriately and at their peak so that amplitude data were accurate. Central reading also ensured consistency in BAEP interpretation. Analysis population included all subjects who received at least 1 dose of study intervention. Number of subjects analyzed signifies number of subjects who were evaluable for this endpoint. n = x, y in the following table represents the number of evaluable subjects in the Ritlecitinib 200/50 mg QD and Placebo arms, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6 and Month 9 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase)
    End point values
    		 Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    34
    34
    Units: Microvolts (μV)
    least squares mean (confidence interval 95%)
        Month 6 (n = 34, 34)
    -0.047 (-0.082 to -0.013)
    -0.019 (-0.053 to 0.015)
        Month 9 (n = 31, 32)
    -0.045 (-0.082 to -0.008)
    -0.049 (-0.085 to -0.012)
    Statistical analysis title
    		 LS Mean Difference (Ritlecitinib vs Placebo)
    Statistical analysis description
    Month 9
    Comparison groups
    Ritlecitinib 200/50 mg QD v Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 [3]
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    0.003
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.049
         upper limit
    		 0.056
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0261
    Notes
    [3] - Linear mixed-effects model with baseline, treatment group, visit (Month 6 and Month 9) and treatment group by visit interaction as fixed effects, and subject as a random effect with an unstructured covariance matrix assumption was used.
    Statistical analysis title
    		 LS Mean Difference (Ritlecitinib vs Placebo)
    Statistical analysis description
    Month 6
    Comparison groups
    Ritlecitinib 200/50 mg QD v Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 [4]
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    -0.028
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.076
         upper limit
    		 0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0242
    Notes
    [4] - Linear mixed-effects model with baseline, treatment group, visit (Month 6 and Month 9) and treatment group by visit interaction as fixed effects, and subject as a random effect with an unstructured covariance matrix assumption was used.

    Secondary: Number of Subjects With Absence of Wave V on BAEP at Stimulus Intensities Ranging From 80 dB to 40 dB From Right Side up to Month 9

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    End point title
    		 Number of Subjects With Absence of Wave V on BAEP at Stimulus Intensities Ranging From 80 dB to 40 dB From Right Side up to Month 9
    End point description
    Absence of wave V on BAEP at stimulus intensities ranging from 80dB to 40dB were summarized descriptively using number of subjects by treatment group at each intensity level. Analysis population included all subjects who received at least 1 dose of study intervention. Number of subjects analyzed signifies number of subjects who were evaluable for this endpoint. n = x, y in the following table represents the number of subjects at each visit in the Ritlecitinib 200/50 mg QD and Placebo arms, respectively. One subject had fluctuating absence of Wave V at lower intensities. Hearing sensitivity remained normal from screening through Month 9. The case was reviewed by a panel of neuroaudiology experts who concluded that there was no evidence of neural transmission abnormality in the auditory nerve or auditory brainstem and that the likely explanation for the absence of Wave V was that the evoked response amplitude was too small for it to be identified within the electroencephalogram (EEG).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6 and Month 9
    End point values
    		 Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    36
    35
    Units: Subjects
        Baseline-80dB normal hearing level (nHL) (n=36,35)
    0
    0
        Baseline - 70 dB nHL (n = 36, 35)
    0
    0
        Baseline - 60 dB nHL (n = 36, 35)
    0
    0
        Baseline - 50 dB nHL (n = 36, 35)
    0
    0
        Baseline - 40 dB nHL (n = 36, 35)
    0
    0
        Month 6 - 80 dB nHL (n = 34, 34)
    0
    0
        Month 6 - 70 dB nHL (n = 34, 34)
    0
    0
        Month 6 - 60 dB nHL (n = 34, 34)
    0
    0
        Month 6 - 50 dB nHL (n = 34, 34)
    0
    0
        Month 6 - 40 dB nHL (n = 34, 34)
    0
    0
        Month 9 - 80 dB nHL (n = 31, 32)
    0
    0
        Month 9 - 70 dB nHL (n = 31, 32)
    0
    0
        Month 9 - 60 dB nHL (n = 31, 32)
    0
    0
        Month 9 - 50 dB nHL (n = 31, 32)
    0
    0
        Month 9 - 40 dB nHL (n = 31, 32)
    1
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Absence of Wave V on BAEP at Stimulus Intensities Ranging From 80 dB to 40 dB From Left Side up to Month 9

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    End point title
    		 Number of Subjects With Absence of Wave V on BAEP at Stimulus Intensities Ranging From 80 dB to 40 dB From Left Side up to Month 9
    End point description
    Absence of wave V on BAEP at stimulus intensities ranging from 80dB to 40dB were summarized descriptively using number of subjects by treatment group at each intensity level. Analysis population included all subjects who received at least 1 dose of study intervention. Number of subjects analyzed signifies number of subjects who were evaluable for this endpoint. n = x, y in the following table represents the number of evaluable subjects in the Ritlecitinib 200/50 mg QD and Placebo arms, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6 and Month 9
    End point values
    		 Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    36
    35
    Units: Subjects
        Baseline - 80 dB nHL (n = 36, 35)
    0
    0
        Baseline - 70 dB nHL (n = 36, 35)
    0
    0
        Baseline - 60 dB nHL (n = 36, 35)
    0
    0
        Baseline - 50 dB nHL (n = 36, 35)
    0
    0
        Baseline - 40 dB nHL (n = 36, 35)
    0
    0
        Month 6 - 80 dB nHL (n = 34, 34)
    0
    0
        Month 6 - 70 dB nHL (n = 34, 34)
    0
    0
        Month 6 - 60 dB nHL (n = 34, 34)
    0
    0
        Month 6 - 50 dB nHL (n = 34, 34)
    0
    0
        Month 6 - 40 dB nHL (n = 34, 34)
    0
    0
        Month 9 - 80 dB nHL (n = 31, 32)
    0
    0
        Month 9 - 70 dB nHL (n = 31, 32)
    0
    0
        Month 9 - 60 dB nHL (n = 31, 32)
    0
    0
        Month 9 - 50 dB nHL (n = 31, 32)
    0
    0
        Month 9 - 40 dB nHL (n = 31, 32)
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse events (TESAEs)

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    End point title
    		 Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse events (TESAEs)
    End point description
    An adverse event (AE) was any untoward medical occurrence in a subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Seriousness of an AE was assessed under the criteria of serious adverse event (SAE). An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect, etc. Treatment-emergent events were with onset date occurring during the on-treatment period. Relatedness to study treatment was determined by the investigator. Analysis population included all subjects taking at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Ritlecitinib 200/50 mg QD Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    36
    32
    35
    31
    Units: Subjects
        TEAE (All-Causality)
    29
    3
    22
    3
        TEAE (Treatment-Related)
    9
    0
    5
    1
        TESAE (All-Causality)
    0
    1
    1
    0
        TESAE (Treatment-Related)
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects Who Discontinued From Study Due to Adverse Event (AEs)

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    End point title
    		 Number of Subjects Who Discontinued From Study Due to Adverse Event (AEs)
    End point description
    An AE was any untoward medical occurrence in a subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Subjects who had an AE record that indicated that the AE caused the subject to be discontinued from the study. Relatedness to study treatment was determined by the investigator. Analysis population included all subjects taking at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Ritlecitinib 200/50 mg QD Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    36
    32
    35
    31
    Units: Subjects
        Due to All-Causality AEs
    0
    1
    0
    0
        Due to Treatment-Related AEs
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects Who Discontinued Study Drug Due to AE and Continued Study

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    End point title
    		 Number of Subjects Who Discontinued Study Drug Due to AE and Continued Study
    End point description
    An AE was any untoward medical occurrence in a subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. This Outcome Measures presented the number of subjects who had an AE record that indicated that action taken with study treatment was drug withdrawn but AE did not cause the subject to be discontinued from study. Relatedness to study treatment was determined by the investigator. Analysis population included all subjects taking at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Ritlecitinib 200/50 mg QD Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    36
    32
    35
    31
    Units: Subjects
        Due to All-Causality AEs
    1
    0
    0
    0
        Due to Treatment-Related AEs
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Temporary Drug Discontinuation Due to AEs

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    End point title
    		 Number of Subjects With Temporary Drug Discontinuation Due to AEs
    End point description
    An AE was any untoward medical occurrence in a subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of subjects with temporary drug discontinuation due to both all-causality and treatment-related AEs are presented below. Relatedness to study treatment was determined by the investigator. Analysis population included all subjects taking at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Ritlecitinib 200/50 mg QD Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    36
    32
    35
    31
    Units: Subjects
        Due to All-Causality AEs
    6
    0
    1
    0
        Due to Treatment-Related AEs
    3
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinically Significant Abnormalities in Vital Signs

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    End point title
    		 Number of Subjects With Clinically Significant Abnormalities in Vital Signs
    End point description
    Oral, tympanic, or axillary temperature, pulse rate, respiratory rate, and blood pressure (BP) were assessed. BP and pulse measurements were assessed in a chair, back supported and arms bared (free of restrictions such as rolled-up sleeves, etc) and supported at heart level. Measurements were taken on the same arm at each visit (preferably non-dominant) with a completely automated device. Pulse rate was measured at approximately the same time as BP for a minimum of 30 seconds. BP and pulse measurements should be preceded by at least 5 minutes of rest for the subject in a quiet setting without distractions (eg, television, cell phones). Subjects refrained from smoking or ingesting caffeine during the 30 minutes preceding the measurements. The clinical significance was determined by the investigator. Analysis population included all subjects taking at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Ritlecitinib 200/50 mg QD Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    36
    32
    35
    31
    Units: Subjects
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinically Significant Abnormalities in Clinical Laboratory Values

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    End point title
    		 Number of Subjects With Clinically Significant Abnormalities in Clinical Laboratory Values
    End point description
    Safety laboratory assessments included the categories of Hematology, Chemistry, Urinalysis and other tests. The clinical significance was determined by the investigator. Analysis population included all subjects taking at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    24 months
    End point values
    		 Ritlecitinib 200/50 mg QD Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    36
    32
    35
    31
    Units: Subjects
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Change From Baseline in Overall Severity of Alopecia Tool (SALT) Scores up to Month 9

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    End point title
    		 Change From Baseline in Overall Severity of Alopecia Tool (SALT) Scores up to Month 9
    End point description
    SALT is a quantitative assessment of AA severity based on scalp terminal hair loss. The overall SALT score included hair loss regardless of etiology (ie, scalp hair loss due to both non-AA and AA) and was collected at study visits. The Overall SALT Score ranged from 0 to 100%, with higher scores representing greater amount of hair loss. Analysis population included all randomized subjects taking at least 1 dose of study intervention. Number of subjects analyzed signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Months 3, 6 and 9 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase)
    End point values
    		 Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    35
    35
    Units: Units on a scale
    least squares mean (confidence interval 95%)
        Month 3
    -23.0 (-29.70 to -16.25)
    -2.7 (-9.39 to 4.06)
        Month 6
    -35.2 (-44.55 to -25.81)
    -5.1 (-14.44 to 4.18)
        Month 9
    -38.2 (-47.46 to -28.86)
    -6.8 (-16.08 to 2.40)
    No statistical analyses for this end point

    Secondary: Change From Baseline in Alopecia Areata - Severity of Alopecia Tool (AA-SALT) Score up to Month 9

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    End point title
    		 Change From Baseline in Alopecia Areata - Severity of Alopecia Tool (AA-SALT) Score up to Month 9
    End point description
    SALT is a quantitative assessment of AA severity based on scalp terminal hair loss. AA-SALT is amount of scalp hair loss due to AA. AA-SALT score in Placebo-Controlled Phase = overall SALT score – non-AA SALT score at Month 6 (for those subjects who entered Active Therapy Extension Phase at Month 6) or Month 9 (non-AA SALT: scalp hair loss other than that due to AA). AA-SALT Score ranged from 0 to 100%, with higher scores representing greater amount of hair loss. Analysis population included all randomized subjects taking at least 1 dose of study intervention. Number of subjects analyzed signifies number of subjects who were evaluable for this endpoint. n = x, y below represents the number of evaluable subjects in Ritlecitinib 200/50 mg and Placebo arms, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Months 3, 6 and 9 (Baseline was defined as the last non-missing measurement obtained before the first dose in the placebo-controlled phase)
    End point values
    		 Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    35
    35
    Units: Units on a scale
    least squares mean (confidence interval 95%)
        Month 3 (n = 35, 35)
    -23.0 (-29.70 to -16.25)
    -2.7 (-9.39 to 4.06)
        Month 6 (n = 34, 35)
    -35.2 (-44.55 to -25.81)
    -5.1 (-14.44 to 4.18)
        Month 9 (n = 32, 31)
    -38.2 (-47.46 to -28.87)
    -6.8 (-16.08 to 2.40)
    No statistical analyses for this end point

    Secondary: Number of Subjects With Patient's Global Impression of Change (PGI-C) Response up to Month 9

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    End point title
    		 Number of Subjects With Patient's Global Impression of Change (PGI-C) Response up to Month 9
    End point description
    The PGI-C asked the subjects to evaluate the improvement or worsening of their AA as compared to the start of the study using a single item, “Since the start of the study, my alopecia areata has: …”. The subjects selected one of seven responses ranging from "greatly improved" to "greatly worsened". This Outcome Measure presented the number of subjects with PGI-C response which was defined as "greatly improved" or "moderately improved". Subjects with missing PGI-C scores were considered as non-responders. Analysis population included all randomized subjects taking at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Months 1, 3, 6 and 9
    End point values
    		 Ritlecitinib 200/50 mg QD Placebo -> Ritlecitinib 200/50 mg QD
    Number of subjects analysed
    36
    35
    Units: Subjects
        Month 1
    4
    3
        Month 3
    20
    6
        Month 6
    21
    10
        Month 9
    19
    6
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    24 months
    Adverse event reporting additional description
    Same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as non-serious in another subject, or 1 subject may have experienced both serious and non-serious event during the study.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Placebo -> Ritlecitinib 200/50 mg QD
    Reporting group description
    		 In the 9-month Placebo-Controlled Phase, each subject received a total of 4 tablets of Placebo QD during the initial 4-week period, and received 1 tablet of Placebo QD during the remainder of that study phase. In the 15-month Active Therapy Extension Phase, each subject received Ritlecitinib 200 mg QD (50 mg/tablet ×4) during the initial 4-week period, and then received 1 tablet of Ritlecitinib 50 mg QD during the remainder of this phase.

    Reporting group title
    Ritlecitinib 200/50 mg QD
    Reporting group description
    		 In the 9-month Placebo-Controlled Phase, each subject received Ritlecitinib 200 mg QD (50 mg/tablet ×4) during the initial 4-week period, and received 1 tablet of Ritlecitinib 50 mg QD during the remainder of that study phase. In the 15-month Active Therapy Extension Phase, each subject received 1 tablet QD of Ritlecitinib 50 mg and 3 tablets of placebo QD during the initial 4-week period, and then received 1 tablet of Ritlecitinib 50 mg QD during the remainder of this phase.

    Serious adverse events
    		 Placebo -> Ritlecitinib 200/50 mg QD Ritlecitinib 200/50 mg QD
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 36 (2.78%)
         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 / 35 (2.86%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Takayasu's arteritis
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo -> Ritlecitinib 200/50 mg QD Ritlecitinib 200/50 mg QD
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    23 / 35 (65.71%)
    29 / 36 (80.56%)
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 35 (0.00%)
    2 / 36 (5.56%)
         occurrences all number
    0
    2
    Injury, poisoning and procedural complications
    Limb injury
         subjects affected / exposed
    2 / 35 (5.71%)
    0 / 36 (0.00%)
         occurrences all number
    2
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 35 (2.86%)
    3 / 36 (8.33%)
         occurrences all number
    1
    3
    Headache
         subjects affected / exposed
    1 / 35 (2.86%)
    4 / 36 (11.11%)
         occurrences all number
    1
    5
    Hypoaesthesia
         subjects affected / exposed
    3 / 35 (8.57%)
    1 / 36 (2.78%)
         occurrences all number
    4
    1
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    2 / 35 (5.71%)
    0 / 36 (0.00%)
         occurrences all number
    2
    0
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 35 (0.00%)
    2 / 36 (5.56%)
         occurrences all number
    0
    2
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 35 (0.00%)
    3 / 36 (8.33%)
         occurrences all number
    0
    4
    Nausea
         subjects affected / exposed
    3 / 35 (8.57%)
    1 / 36 (2.78%)
         occurrences all number
    4
    1
    Vomiting
         subjects affected / exposed
    1 / 35 (2.86%)
    3 / 36 (8.33%)
         occurrences all number
    1
    3
    Respiratory, thoracic and mediastinal disorders
    Rhinitis allergic
         subjects affected / exposed
    0 / 35 (0.00%)
    2 / 36 (5.56%)
         occurrences all number
    0
    2
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    2 / 35 (5.71%)
    2 / 36 (5.56%)
         occurrences all number
    2
    2
    Pruritus
         subjects affected / exposed
    2 / 35 (5.71%)
    0 / 36 (0.00%)
         occurrences all number
    4
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 35 (0.00%)
    2 / 36 (5.56%)
         occurrences all number
    0
    2
    Infections and infestations
    Acne pustular
         subjects affected / exposed
    0 / 35 (0.00%)
    4 / 36 (11.11%)
         occurrences all number
    0
    5
    COVID-19
         subjects affected / exposed
    3 / 35 (8.57%)
    3 / 36 (8.33%)
         occurrences all number
    3
    3
    Nasopharyngitis
         subjects affected / exposed
    2 / 35 (5.71%)
    3 / 36 (8.33%)
         occurrences all number
    3
    4
    Tonsillitis
         subjects affected / exposed
    0 / 35 (0.00%)
    2 / 36 (5.56%)
         occurrences all number
    0
    2
    Sinusitis
         subjects affected / exposed
    1 / 35 (2.86%)
    2 / 36 (5.56%)
         occurrences all number
    1
    2
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 35 (2.86%)
    3 / 36 (8.33%)
         occurrences all number
    1
    3
    Urinary tract infection
         subjects affected / exposed
    3 / 35 (8.57%)
    0 / 36 (0.00%)
         occurrences all number
    4
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Apr 2021
    Updated Schedule of Activities and Section 4.1 Study Design; revised Inclusion and Exclusion Criteria; Section 6.2.1 Preparation and Dispensing was updated to add that at the EOP visit; updated Section 6.5.3 Vaccinations, Section 8.2.6 Audiological Evaluations, Section 8.2.7 Brainstem Auditory Evoked Potential Evaluations, Section 8.2.10.1.3 Subsequent Tuberculosis Testing, Section 8.2.11.1. Columbia Suicide Severity Rating Scale (C-SSRS); Section 8.2.9.2.2 Canfield Rash Manual was updated to Canfield Photography User Manual; In Section 8.2.14 The name of the ‘Rater Qualifications Manual’ was updated to ‘Rater Assessment Manual’; Section 8.3.6 Cardiovascular and Death Events, was updated to reflect the adjudication process; Section 8.3.8 Adverse Events of Special Interest, was updated to add a reference to the section with the definition and the reporting process; deleted Section 8.10 Health Economics; updated Appendix 4, 6, 7, 9.
    28 Apr 2022
    In order to allow study subjects continued access to study intervention with collection of additional long-term safety and efficacy data, study duration was extended up to 60 months (or until availability of commercial product in the country or until the sponsor terminates the study in that country). The endpoints were updated as a result of the study extension. Added ECG analysis under safety endpoints at TP1 and TP2 phases only. Added detail on permanent discontinuation and defined the Observation Period. Update was made in alignment with Investigator Brochure version 8.0 December 2021, and also to clarify the safety of PF-06651600. Update was made to clarify the safety of PF-06651600. Mean Clinical AUC and Calculated Safety Margin updated. Added additional clarifications on the contraception check. Updated the blinding approach in the study. Updated the amount of blood to be collected from each subject. Clarified when an interim analysis may be needed. Updated language regarding events requiring submission to an adjudication/review committee, and text regarding confirmation of post-menopausal status during the study. Updated hemoglobin values requiring re-testing in Table 3.

    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.
    The study is still ongoing. This report reflects data collected up to PCD (04 January 2022), and will be updated after completion of the whole study.
    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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