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    Clinical Trial Results:
    A 24 week, randomised, assessor blinded, active-controlled, parallel group, phase 3, 2 arm trial to compare the efficacy and safety of delgocitinib cream 20 mg/g twice-daily with alitretinoin capsules once-daily in adult participants with severe chronic hand eczema

    Summary
    EudraCT number
    		 2021-003543-16
    Trial protocol
    		 DE   IT   ES   FR   AT   PL   NO   SK  
    Global end of trial date
    05 Dec 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Oct 2024
    First version publication date
    25 Oct 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    LP0133-1528
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05259722
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    LEO Pharma A/S
    Sponsor organisation address
    Industriparken 55, Ballerup, Denmark, 2750
    Public contact
    Clinical Disclosure, LEO Pharma A/S, disclosure@leo-pharma.com
    Scientific contact
    Clinical Disclosure, LEO Pharma A/S, disclosure@leo-pharma.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
    19 Feb 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    08 Nov 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Dec 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the efficacy and health-related quality of life of twice-daily topical application of delgocitinib cream with once-daily oral administration of alitretinoin capsules in the treatment of patients with severe CHE.
    Protection of trial subjects
    This trial was conducted in accordance with the protocol and consensus ethical principles derived from international guidelines including the Declaration of Helsinki, CIOMS International Ethical Guidelines, applicable ICH GCP guidelines, and other applicable laws and regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 N/A
    Actual start date of recruitment
    15 Jun 2022
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    Austria: 5
    Country: Number of subjects enrolled
    France: 30
    Country: Number of subjects enrolled
    Germany: 136
    Country: Number of subjects enrolled
    Italy: 22
    Country: Number of subjects enrolled
    Norway: 2
    Country: Number of subjects enrolled
    Poland: 180
    Country: Number of subjects enrolled
    Slovakia: 14
    Country: Number of subjects enrolled
    Spain: 64
    Country: Number of subjects enrolled
    Canada: 54
    Worldwide total number of subjects
    513
    EEA total number of subjects
    453
    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)
    471
    From 65 to 84 years
    42
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The trial enrolled adult participants with severe CHE and with a documented inadequate response to treatment with TCS or for whom TCS were documented to be otherwise medically inadvisable.

    Pre-assignment
    Screening details
    		 Randomization was stratified by subtype (hyperkeratotic/non-hyperkeratotic) and region (North America/Europe).

    Period 1
    Period 1 title
    Overall study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Due to the different administration routes for the 2 IMPs, participants were not blinded to treatment assignment. To ensure unbiased clinical assessments, efficacy (IGA-CHE and HECSI) was evaluated by a blinded assessor.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Delgocitinib Cream 20 mg/g
    Arm description
    		 Twice-daily topical application for up to 24 weeks. Delgocitinib: Cream for topical application 20 mg/g. There was a possibility to stop treatment after 16 weeks if IGA 0/1 was obtained.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Delgocitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Cream
    Routes of administration
    Topical
    Dosage and administration details
    20 mg/g milligram(s)/gram twice daily for up to 24 weeks

    Arm title
    		 Alitretinoin Capsules 30 mg Per Capsule
    Arm description
    		 1 capsule per day for up to 24 weeks Toctino: 1 capsule Toctino 30 mg per day; optional reduction to 10 mg per day in case unacceptable adverse reactions to the higher dose occur. There was a possibility to stop treatment after 12 weeks if IGA 0/1 was obtained.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Alitretinoin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    1 capsule per day for up to 24 weeks. Toctino: 1 capsule toctino 30 mg per day; optional reduction to 10 mg per day in case unacceptable adverse reactions to the higher dose occur

    Number of subjects in period 1
    		Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule
    Started
    254
    259
    Completed
    219
    154
    Not completed
    35
    105
         Consent withdrawn by subject
    15
    33
         Discontinuation of IMP, related to COVID-19
    1
    -
         Adverse event, non-fatal
    2
    24
         Various reasons
    3
    9
         Not exposed to IMP
    1
    12
         Lost to follow-up
    5
    1
         Lack of efficacy
    8
    26

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Delgocitinib Cream 20 mg/g
    Reporting group description
    		 Twice-daily topical application for up to 24 weeks. Delgocitinib: Cream for topical application 20 mg/g. There was a possibility to stop treatment after 16 weeks if IGA 0/1 was obtained.

    Reporting group title
    Alitretinoin Capsules 30 mg Per Capsule
    Reporting group description
    		 1 capsule per day for up to 24 weeks Toctino: 1 capsule Toctino 30 mg per day; optional reduction to 10 mg per day in case unacceptable adverse reactions to the higher dose occur. There was a possibility to stop treatment after 12 weeks if IGA 0/1 was obtained.

    Reporting group values
    		 Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule Total
    Number of subjects
    		 254 259 513
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 45.4 ( 13.78 ) 44.0 ( 14.56 ) -
    Gender categorical
    Units: Subjects
        Female
    		 167 167 334
        Male
    		 87 92 179
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 2 2 4
        Asian
    		 9 5 14
        Native Hawaiian or Other Pacific Islander
    		 0 1 1
        Black or African American
    		 2 3 5
        White
    		 237 240 477
        More than one race
    		 1 6 7
        Unknown or Not Reported
    		 3 2 5
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 22 14 36
        Not Hispanic or Latino
    		 226 241 467
        Unknown or Not Reported
    		 6 4 10

    End points

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    End points reporting groups
    Reporting group title
    Delgocitinib Cream 20 mg/g
    Reporting group description
    		 Twice-daily topical application for up to 24 weeks. Delgocitinib: Cream for topical application 20 mg/g. There was a possibility to stop treatment after 16 weeks if IGA 0/1 was obtained.

    Reporting group title
    Alitretinoin Capsules 30 mg Per Capsule
    Reporting group description
    		 1 capsule per day for up to 24 weeks Toctino: 1 capsule Toctino 30 mg per day; optional reduction to 10 mg per day in case unacceptable adverse reactions to the higher dose occur. There was a possibility to stop treatment after 12 weeks if IGA 0/1 was obtained.

    Primary: Change in HECSI Score From Baseline to Week 12

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    End point title
    		 Change in HECSI Score From Baseline to Week 12
    End point description
    The Hand Eczema Severity Index (HECSI) is an instrument used in clinical trials to rate the severity of 6 clinical signs (erythema, infiltration/papulation, vesicles, fissures, scaling, and oedema) and the extent of the lesions in each of the 5 hand regions (fingertips, fingers [except fingertips], palm of hands, back of hands, and wrists) by use of standard scales. The HECSI score will range from 0 (lowest possible score) to 360 (highest possible score).
    End point type
    Primary
    End point timeframe
    12 weeks
    End point values
    		 Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects analysed
    249
    250
    Units: score on a scale
        arithmetic mean (standard error)
    -67.6 ( 3.37 )
    -51.5 ( 3.36 )
    Statistical analysis title
    		 Delgocitinib cream 20 mg/g vs alitretinoin
    Statistical analysis description
    The change from baseline was analysed using an ANCOVA model with effects of treatment group, hyperkeratotic/non-hyperkeratotic subtype and baseline value of the score. Missing data was imputed with WOCF. Data after initiation of rescue treatment or permanent discontinuation of IMP was treated as missing.
    Comparison groups
    Delgocitinib Cream 20 mg/g v Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects included in analysis
    499
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -16.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.28
         upper limit
    		 -8.86

    Secondary: HECSI-90 at Week 12

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    End point title
    		 HECSI-90 at Week 12
    End point description
    The Hand Eczema Severity Index (HECSI) is an instrument used in clinical trials to rate the severity of 6 clinical signs (erythema, infiltration/papulation, vesicles, fissures, scaling, and oedema) and the extent of the lesions in each of the 5 hand regions (fingertips, fingers [except fingertips], palm of hands, back of hands, and wrists) by use of standard scales. The HECSI score will range from 0 (lowest possible score) to 360 (highest possible score). HECSI-90 is defined as at least 90% improvement in HECSI score from baseline.
    End point type
    Secondary
    End point timeframe
    12 weeks
    End point values
    		 Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects analysed
    249
    250
    Units: Participants
    96
    65
    Statistical analysis title
    		 Delgocitinib cream 20 mg/g vs alitretinoin
    Statistical analysis description
    The difference in response rates was analysed using the Cochran-Mantel-Haenszel test stratified by hyperkeratotic/non-hyperkeratotic subtype. Missing data was imputed as non-response. Data after initiation of rescue treatment or permanent discontinuation of IMP was treated as missing.
    Comparison groups
    Delgocitinib Cream 20 mg/g v Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects included in analysis
    499
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    12.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.34
         upper limit
    		 20.78

    Secondary: IGA-CHE TS at Week 12

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    End point title
    		 IGA-CHE TS at Week 12
    End point description
    The Investigator's Global Assessment for chronic hand eczema (IGA-CHE) is an instrument used in clinical trials to rate the severity of the participant's global chronic hand eczema (CHE) and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). IGA-CHE treatment success (IGA-CHE TS) is defined as an IGA-CHE score of 0 (clear) or 1 (almost clear) with a ≥2-step improvement from baseline.
    End point type
    Secondary
    End point timeframe
    12 weeks
    End point values
    		 Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects analysed
    250
    253
    Units: Participants
    68
    42
    Statistical analysis title
    		 Delgocitinib cream 20 mg/g vs alitretinoin
    Statistical analysis description
    The difference in response rates was analysed using the Cochran-Mantel-Haenszel test stratified by hyperkeratotic/non-hyperkeratotic subtype. Missing data was imputed as non-response. Data after initiation of rescue treatment or permanent discontinuation of IMP was treated as missing.
    Comparison groups
    Delgocitinib Cream 20 mg/g v Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects included in analysis
    503
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.004
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    10.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.31
         upper limit
    		 17.87

    Secondary: Change in HESD Itch Score (Weekly Average) From Baseline to Week 12

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    End point title
    		 Change in HESD Itch Score (Weekly Average) From Baseline to Week 12
    End point description
    The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. This endpoint will only assess the 'itch' component.
    End point type
    Secondary
    End point timeframe
    12 weeks
    End point values
    		 Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects analysed
    238
    238
    Units: score on a scale
        arithmetic mean (standard error)
    -3.0 ( 0.22 )
    -2.4 ( 0.21 )
    Statistical analysis title
    		 Delgocitinib cream 20 mg/g vs alitretinoin
    Statistical analysis description
    The change from baseline was analysed using an ANCOVA model with effects of treatment group, hyperkeratotic/non-hyperkeratotic subtype and baseline value of the score. Missing data was imputed with WOCF. Data after initiation of rescue treatment or permanent discontinuation of IMP was treated as missing.
    Comparison groups
    Delgocitinib Cream 20 mg/g v Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects included in analysis
    476
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.005
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.12
         upper limit
    		 -0.2

    Secondary: Change in HESD Pain Score (Weekly Average) From Baseline to Week 12

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    End point title
    		 Change in HESD Pain Score (Weekly Average) From Baseline to Week 12
    End point description
    The Hand Eczema Symptom Diary (HESD) is an eDiary in which participants will assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale throughout the trial on a daily basis. This endpoint will only assess the 'pain' component.
    End point type
    Secondary
    End point timeframe
    12 weeks
    End point values
    		 Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects analysed
    238
    238
    Units: score on a scale
        arithmetic mean (standard error)
    -2.9 ( 0.23 )
    -2.3 ( 0.23 )
    Statistical analysis title
    		 Delgocitinib cream 20 mg/g vs alitretinoin
    Statistical analysis description
    The change from baseline was analysed using an ANCOVA model with effects of treatment group, hyperkeratotic/non-hyperkeratotic subtype and baseline value of the score. Missing data was imputed with WOCF. Data after initiation of rescue treatment or permanent discontinuation of IMP was treated as missing.
    Comparison groups
    Delgocitinib Cream 20 mg/g v Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects included in analysis
    476
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.018
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.08
         upper limit
    		 -0.1

    Secondary: AUC of HECSI-90 From Baseline up to Week 24

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    End point title
    		 AUC of HECSI-90 From Baseline up to Week 24
    End point description
    The Hand Eczema Severity Index (HECSI) is an instrument used in clinical trials to rate the severity of 6 clinical signs (erythema, infiltration/papulation, vesicles, fissures, scaling, and oedema) and the extent of the lesions in each of the 5 hand regions (fingertips, fingers [except fingertips], palm of hands, back of hands, and wrists) by use of standard scales. The HECSI score will range from 0 (lowest possible score) to 360 (highest possible score). HECSI-90 is defined as at least 90% improvement in HECSI score from baseline. The area under the curve (AUC) at participant level will be determined as follows: 1 will be assigned when response is observed and 0 otherwise. The AUC is interpreted as number of days with 90% reduction in HECSI score until Week 24.
    End point type
    Secondary
    End point timeframe
    24 weeks
    End point values
    		 Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects analysed
    249
    250
    Units: score on a scale
        arithmetic mean (standard error)
    51.1 ( 4.11 )
    43.5 ( 4.22 )
    Statistical analysis title
    		 Delgocitinib cream 20 mg/g vs alitretinoin
    Statistical analysis description
    The AUC was analysed using a robust ANCOVA model with effects of treatment group, hyperkeratotic/non-hyperkeratotic subtype and baseline value of the score. Missing data was imputed with WOCF. Data after initiation of rescue treatment or permanent discontinuation of IMP was treated as missing.
    Comparison groups
    Delgocitinib Cream 20 mg/g v Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects included in analysis
    499
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    14.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.81
         upper limit
    		 22.86

    Secondary: AUC of Change From Baseline in DLQI Score up to Week 24

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    End point title
    		 AUC of Change From Baseline in DLQI Score up to Week 24
    End point description
    The Dermatology Life Quality Index (DLQI) is a validated questionnaire consisting of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their quality of life over the last week. The DLQI score is the sum of the 10 items (score ranging from 0 to 30). The area under the curve (AUC) at patient level will be determined from the change from baseline in DLQI score estimated piecewise from Week 0 to Week 24. Differences will be analysed with opposite sign to interpret positive area as improvement in scores and negative area as worsening.
    End point type
    Secondary
    End point timeframe
    24 weeks
    End point values
    		 Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects analysed
    230
    236
    Units: score on a scale
        arithmetic mean (standard error)
    1124.7 ( 61.37 )
    790.7 ( 62.67 )
    Statistical analysis title
    		 Delgocitinib cream 20 mg/g vs alitretinoin
    Statistical analysis description
    The AUC was analysed using a robust ANCOVA model with effects of treatment group, hyperkeratotic/non-hyperkeratotic subtype and baseline value of the score. Missing data was imputed with WOCF. Data after initiation of rescue treatment or permanent discontinuation of IMP was treated as missing.
    Comparison groups
    Delgocitinib Cream 20 mg/g v Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects included in analysis
    466
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    334
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 195.69
         upper limit
    		 472.26

    Secondary: Change in HECSI Score From Baseline to Week 24

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    End point title
    		 Change in HECSI Score From Baseline to Week 24
    End point description
    The Hand Eczema Severity Index (HECSI) is an instrument used in clinical trials to rate the severity of 6 clinical signs (erythema, infiltration/papulation, vesicles, fissures, scaling, and oedema) and the extent of the lesions in each of the 5 hand regions (fingertips, fingers [except fingertips], palm of hands, back of hands, and wrists) by use of standard scales. The HECSI score will range from 0 (lowest possible score) to 360 (highest possible score).
    End point type
    Secondary
    End point timeframe
    24 weeks
    End point values
    		 Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects analysed
    249
    250
    Units: score on a scale
        arithmetic mean (standard error)
    -69.6 ( 3.78 )
    -45.1 ( 3.77 )
    Statistical analysis title
    		 Delgocitinib cream 20 mg/g vs alitretinoin
    Statistical analysis description
    The change from baseline was analysed using an ANCOVA model with effects of treatment group, hyperkeratotic/non-hyperkeratotic subtype and baseline value of the score. Missing data was imputed with WOCF. Data after initiation of rescue treatment or permanent discontinuation of IMP was treated as missing.
    Comparison groups
    Delgocitinib Cream 20 mg/g v Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects included in analysis
    499
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.001 [2]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -24.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -32.55
         upper limit
    		 -16.36
    Notes
    [1] - Non-inferiority (margin=10) was tested before superiority.
    [2] - Non-inferiority (margin=10) p-value <0.001, superiority p-value <0.001

    Secondary: Number of Treatment-emergent AEs From Baseline up to Week 26

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    End point title
    		 Number of Treatment-emergent AEs From Baseline up to Week 26
    End point description
    An adverse event (AE) will be considered treatment emergent if started after the first application of investigational medicinal product (IMP), or if started before the first application of IMP and worsened in severity after first dose of IMP.
    End point type
    Secondary
    End point timeframe
    26 weeks
    End point values
    		 Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects analysed
    253
    247
    Units: events
    280
    620
    No statistical analyses for this end point

    Secondary: Number of Treatment-emergent SAEs From Baseline up to Week 26

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    End point title
    		 Number of Treatment-emergent SAEs From Baseline up to Week 26
    End point description
    A serious adverse event (SAE) will be considered treatment emergent if started after the first application of investigational medicinal product (IMP), or if started before the first application of IMP and worsened in severity after first dose of IMP.
    End point type
    Secondary
    End point timeframe
    26 weeks
    End point values
    		 Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects analysed
    253
    247
    Units: events
    5
    12
    No statistical analyses for this end point

    Secondary: Number of AEs Leading to IMP Discontinuation up to Week 24

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    End point title
    		 Number of AEs Leading to IMP Discontinuation up to Week 24
    End point description
    The investigational medicinal product (IMP) will be discontinued permanently in case of an AE that, in the opinion of the investigator or sponsor's medical expert, contraindicates further dosing. The investigator will assess the relationship between investigational medicinal product (IMP) and the adverse event (AE).
    End point type
    Secondary
    End point timeframe
    24 weeks
    End point values
    		 Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule
    Number of subjects analysed
    253
    247
    Units: events
    4
    44
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From baseline to Week 24
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Delgocitinib Cream 20 mg/g
    Reporting group description
    		 Twice-daily topical application for up to 24 weeks. Delgocitinib: Cream for topical application 20 mg/g. There was a possibility to stop treatment after 12 or 16 weeks if IGA 0/1 was obtained.

    Reporting group title
    Alitretinoin Capsules 30 mg Per Capsule
    Reporting group description
    		 1 capsule per day for up to 24 weeks Toctino: 1 capsule Toctino 30 mg per day; optional reduction to 10 mg per day in case unacceptable adverse reactions to the higher dose occur

    Serious adverse events
    		 Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 253 (1.98%)
    12 / 247 (4.86%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Investigations
    Blood potassium increased
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 253 (0.40%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign salivary gland neoplasm
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Deep vein thrombosis postoperative
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 247 (0.40%)
         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
    Prostatitis
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 247 (0.40%)
         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
    Mediastinal cyst
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Hand dermatitis
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 247 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Gastroenteritis norovirus
         subjects affected / exposed
    1 / 253 (0.40%)
    0 / 247 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    0 / 253 (0.00%)
    1 / 247 (0.40%)
         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: 2%
    Non-serious adverse events
    		 Delgocitinib Cream 20 mg/g Alitretinoin Capsules 30 mg Per Capsule
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    58 / 253 (22.92%)
    143 / 247 (57.89%)
    Investigations
    Blood triglycerides increased
         subjects affected / exposed
    2 / 253 (0.79%)
    7 / 247 (2.83%)
         occurrences all number
    2
    8
    Vascular disorders
    Flushing
         subjects affected / exposed
    0 / 253 (0.00%)
    5 / 247 (2.02%)
         occurrences all number
    0
    6
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 253 (0.40%)
    6 / 247 (2.43%)
         occurrences all number
    1
    6
    Headache
         subjects affected / exposed
    10 / 253 (3.95%)
    79 / 247 (31.98%)
         occurrences all number
    19
    113
    Migraine
         subjects affected / exposed
    2 / 253 (0.79%)
    6 / 247 (2.43%)
         occurrences all number
    2
    7
    Eye disorders
    Dry eye
         subjects affected / exposed
    0 / 253 (0.00%)
    7 / 247 (2.83%)
         occurrences all number
    0
    7
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 253 (0.00%)
    5 / 247 (2.02%)
         occurrences all number
    0
    5
    Lip dry
         subjects affected / exposed
    0 / 253 (0.00%)
    8 / 247 (3.24%)
         occurrences all number
    0
    8
    Nausea
         subjects affected / exposed
    1 / 253 (0.40%)
    14 / 247 (5.67%)
         occurrences all number
    1
    15
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 253 (0.40%)
    5 / 247 (2.02%)
         occurrences all number
    1
    6
    Skin and subcutaneous tissue disorders
    Dermatitis atopic
         subjects affected / exposed
    1 / 253 (0.40%)
    5 / 247 (2.02%)
         occurrences all number
    1
    5
    Eczema
         subjects affected / exposed
    2 / 253 (0.79%)
    5 / 247 (2.02%)
         occurrences all number
    2
    6
    Erythema
         subjects affected / exposed
    1 / 253 (0.40%)
    9 / 247 (3.64%)
         occurrences all number
    1
    10
    Dry skin
         subjects affected / exposed
    3 / 253 (1.19%)
    9 / 247 (3.64%)
         occurrences all number
    3
    9
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 253 (0.79%)
    6 / 247 (2.43%)
         occurrences all number
    2
    6
    Infections and infestations
    COVID-19
         subjects affected / exposed
    5 / 253 (1.98%)
    9 / 247 (3.64%)
         occurrences all number
    5
    9
    Nasopharyngitis
         subjects affected / exposed
    30 / 253 (11.86%)
    34 / 247 (13.77%)
         occurrences all number
    38
    46
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 253 (2.37%)
    8 / 247 (3.24%)
         occurrences all number
    8
    8
    Urinary tract infection
         subjects affected / exposed
    1 / 253 (0.40%)
    10 / 247 (4.05%)
         occurrences all number
    1
    11
    Metabolism and nutrition disorders
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 253 (0.00%)
    9 / 247 (3.64%)
         occurrences all number
    0
    10
    Hypertriglyceridaemia
         subjects affected / exposed
    3 / 253 (1.19%)
    6 / 247 (2.43%)
         occurrences all number
    3
    7

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Apr 2022
    The protocol was amended in order to implement changes from local amendments (UK and Canada).
    24 Jun 2022
    The protocol was amended in order to add the patient reported outcomes PGI-S and PGI-C.

    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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