Efficacy and Safety of Delgocitinib Cream in Discoid Lupus Erythematosus.

• Sponsor: LEO Pharma (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03958955
• Collaborator: (none)
• Enrollment: 27
• Locations: 19
• Arms: 2
• Actual Duration (Months): 9.7
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was a double-blind, multi-centre, randomised, vehicle-controlled, within-subject phase 2a trial. The trial was designed to establish the efficacy and safety of delgocitinib cream in the treatment of adult subjects with discoid lupus erythematosus (DLE).

Condition or Disease	Intervention/Treatment	Phase
Discoid Lupus Erythematosus	Drug: Delgocitinib cream; Drug: Delgocitinib cream vehicle	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This was a phase 2a, within-subject trial design, where all subjects were treated with active treatment on one DLE target lesion and vehicle treatment on another DLE target lesion.This was a phase 2a, within-subject trial design, where all subjects were treated with active treatment on one DLE target lesion and vehicle treatment on another DLE target lesion.
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Twice-daily Application of Delgocitinib Cream 20 mg/g for 6 Weeks in Subjects With Active Discoid Lupus Erythematosus.
• Actual Study Start Date: Jul 9, 2019
• Actual Primary Completion Date: Apr 15, 2020
• Actual Study Completion Date: Apr 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Delgocitinib cream 20 mg/g Delgocitinib cream applied twice daily for 6 weeks	Drug: Delgocitinib cream; Cream for topical application.; Other Names: LEO 124249 cream
Placebo Comparator: Delgocitinib cream vehicle Delgocitinib cream vehicle applied twice daily for 6 weeks	Drug: Delgocitinib cream vehicle; The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.; Other Names: LEO 124249 cream vehicle

Outcome Measures

Primary Outcome Measures

1. Target Lesions With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 6. [Week 6]

   The IGA is an instrument used in clinical trials to rate the severity of the subject's global disease and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). In this trial, the IGA was a lesion-specific assessment and was evaluated separately for each of the 2 target lesions.

Secondary Outcome Measures

1. Number of Adverse Events (AEs) up to Week 6. [Week 0 to Week 6]

   Number of AEs from baseline to Week 6

2. Number of Subjects With AEs up to Week 6. [Week 0 to Week 6]

   Number of subjects with AEs from baseline to Week 6

3. Number of Lesion-specific, Treatment-related AEs up to Week 6. [Week 0 to Week 6]

   The number of lesion-specific, treatment-related AEs per target lesion will be compared for active and vehicle treatment. Lesion-specific AEs are defined as lesional/perilesional AEs (i.e. AE location within the treatment area and/or ≤2 cm from the border of a target lesion).

4. Number of Lesions With ≥2-point Reduction in IGA Score at Week 6 Compared to Baseline. [Week 0 to Week 6]

   The IGA is an instrument used in clinical trials to rate the severity of the subject's global disease and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). In this trial, the IGA was a lesion-specific assessment and was evaluated separately for each of the 2 target lesions.

5. Number of Lesions With ≥2-point Reduction in Erythema Score at Week 6 Compared to Baseline. [Week 0 to Week 6]

   The erythema score is lesion-specific and based on the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the Revised CLASI (RCLASI) which are validated scoring systems to assess disease activity and damage in patients with cutaneous lupus erythematosus. The severity of the erythema is scored on a 4-point scale ranging from 0 to 3. The severity is scored from low to high with 0=absent and 3=dark red, purple/violaceous/crusted/haemorrhagic.

6. Erythema Score at Week 6. [Week 6]

   The erythema score is lesion-specific and based on the CLASI and the RCLASI which are validated scoring systems to assess disease activity and damage in patients with cutaneous lupus erythematosus. The severity of the erythema is scored on a 4-point scale ranging from 0 to 3. The severity is scored from low to high with 0=absent and 3=dark red, purple/violaceous/crusted/haemorrhagic.

7. Total Skin Disease Activity Score (Sum of Scores for Erythema, Scaling/Hyperkeratosis, and Oedema/Infiltration) at Week 6. [Week 6]

   The skin disease activity scores are based on the CLASI and the RCLASI which are validated scoring systems to assess disease activity and damage in patients with cutaneous lupus erythematosus. The total skin disease activity score is defined as the sum of the scores for 3 clinical signs (erythema, scaling/hyperkeratosis, oedema/infiltration) for each target lesion. For the total score and the individual clinical signs, higher scores indicate more severe symptoms. Erythema is scored on a 4-point scale ranging from 0 (absent) to 3 (dark red, purple/violaceous/crusted/haemorrhagic). Hyperkeratosis/scaling is scored on a 3-point scale from 0 (absent) to 2 (verrucous hyperkeratosis). Oedema/infiltration is scored on a 3-point scale from 0 (absent) to 2 (palpable and visible). The total skin disease activity score can therefore range from 0 to 7.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Main Inclusion Criteria:

• Histopathological findings (current or previous) consistent with clinical diagnosis of DLE.

• Unequivocal clinical diagnosis of 2 active DLE target lesions that were <6 months old and amenable for clinical evaluation. This included lesions located on the scalp if they fulfilled all lesion-specific eligibility criteria.

• Target lesion IGA score of at least moderate severity (≥3) at screening and baseline.

• Target lesion erythema score ≥2 at screening and baseline.

Main Exclusion Criteria:

• Target lesion dyspigmentation score of 2 at screening or baseline.

• Target lesion scarring/atrophy score of 2 at screening or baseline.

• Target lesion scarring alopecia score of >0 in scalp lesions at screening or baseline.

• Medical history of systemic lupus erythematosus (SLE) with clinically significant organ involvement (American College of Rheumatology SLE classification criteria no. 6 to 9) including SLE-related pleuritis or pericarditis (by clinical evaluation and electrocardiogram), and neurologic, renal, and/or other major SLE-related organ system involvement. SLE joint involvement was acceptable.

• Subjects with unstable or significant SLE disease activity findings that would, by its progressive nature and/or severity, interfere with the trial evaluation, completion, and/or procedures per the investigator's discretion.

• Other skin conditions at screening or baseline that would interfere with the evaluation of DLE.

• Immunosuppressive/immunomodulating therapy with e.g. methotrexate, cyclosporine, azathioprine, retinoids (both topical and systemic), or dapsone within 4 weeks prior to baseline.

• Systemic prednisolone >7.5 mg/day or changed dose within 4 weeks prior to baseline (nasal and inhaled corticosteroids were allowed).

• Treatment with the following medications:

• Oral antimalarial treatment with hydroxychloroquine >6.5 mg/kg body weight/day, or chloroquine >4 mg/kg body weight/day, or changed dose within 12 weeks prior to baseline.

• Quinacrine combined with either hydroxychloroquine or chloroquine within 12 weeks prior to baseline.

• Drugs known to interact with antimalarials (e.g. digoxin, cimetidine) within 12 weeks prior to baseline.

• Treatment with topical corticosteroids, calcineurin inhibitors, and phosphodiesterase-4 (PDE-4) inhibitors within 2 weeks prior to baseline.

• Use of systemic antibiotics or cutaneously applied antibiotics on the target lesions within 2 weeks prior to baseline.

• Ultraviolet (UV) therapy within 2 weeks prior to baseline.

• Any procedure impairing the skin barrier (e.g. incision) within 2 cm from the border of any of the target lesions within 4 weeks prior to baseline.

• Receipt of live (attenuated) vaccines within 4 weeks prior to baseline.

• Treatment with any marketed biological therapy or investigational biologic agents:

• Any cell-depleting agents including but not limited to rituximab: within 6 months prior to baseline, or until lymphocyte count returned to normal, whichever was longer.

• Other biologics: within 3 months or 5 half-lives, whichever was longer, prior to baseline.

• Unstable or fluctuating use of tobacco within 1 month prior to screening which, in the opinion of the investigator, could affect the natural course of the disease and thus affect the evaluation of the treatment.

• History of any active skin infection within 1 week prior to baseline.

• Clinically significant infection within 4 weeks prior to baseline which, in the opinion of the investigator, could compromise the safety of the subject in the trial, interfere with evaluation of the IMP, or reduce the subject's ability to participate in the trial. Clinically significant infections are defined as:

• A systemic infection.

• A serious skin infection requiring parenteral (intravenous or intramuscular) antibiotics, antiviral, or antifungal medication.

• Tuberculosis requiring treatment within 12 months prior to screening and/or subjects with a positive blood test for tuberculosis at screening. Subjects with high risk of latent tuberculosis (e.g. prior residence in or travel to countries with high prevalence of tuberculosis, close contact with a person with active tuberculosis, or a history of active or latent tuberculosis where an adequate course of treatment cannot be confirmed) must have been tested at screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	LEO Pharma Investigational Site	San Diego	California	United States	92103
2	LEO Pharma Investigational Site	Skokie	Illinois	United States	60077
3	LEO Pharma Investigational Site	Boston	Massachusetts	United States	02115
4	LEO Pharma Investigational Site	Forest Hills	New York	United States	11375
5	LEO Pharma Investigational Site	Cincinnati	Ohio	United States	45219
6	LEO Pharma Investigational Site	Aarhus		Denmark	8200
7	LEO Pharma Investigational site	Hellerup		Denmark	2900
8	LEO Pharma Investigational Site	Odense		Denmark	5000
9	LEO Pharma Investigational Site	Loiré		France	42000
10	LEO Pharma Investigational Site	Nice		France	06202
11	LEO Pharma Investigational Site	Paris		France	75010
12	LEO Pharma Investigational Site	Toulouse		France	31000
13	LEO Pharma Investigational Site	Aachen		Germany	52074
14	LEO Pharma Investigational Site	Berlin		Germany	10117
15	LEO Pharma Investigational Site	Bochum		Germany	44791
16	LEO Pharma Investigational Site	Dresden		Germany	01307
17	LEO Pharma Investigational Site	Duesseldorf		Germany	40225
18	LEO Pharma Investigational Site	Erlangen		Germany	91054
19	LEO Pharma Investigational Site	Oldenburg		Germany	26133

Sponsors and Collaborators

• LEO Pharma

Investigators

• Study Director: Medical Expert, LEO Pharma

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 22, 2019

More Information

Publications

None provided.

• Responsible Party: LEO Pharma
• ClinicalTrials.gov Identifier: NCT03958955
• Other Study ID Numbers: EXP-1373; 2018-003615-22
• First Posted: May 22, 2019
• Last Update Posted: Jun 28, 2021
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lupus Erythematosus, Systemic; Lupus Erythematosus, Discoid

Study Results

Participant Flow

Recruitment Details	37 subjects screened. 27 subjects randomised. 26 subjects completed.
Pre-assignment Detail	A screening visit took place 7 to 28 days before the first application of investigational medicinal product (IMP). To be eligible for participation in the trial each subject had to have at least 2 discoid lupus erythematosus (DLE) target lesions with active disease (referred to as lesions 1 and 2) fulfilling the inclusion criteria.

Arm/Group Title	All Subjects
Arm/Group Description	All 27 subjects received delgocitinib cream 20 mg/g on one DLE target lesion and delgocitinib cream vehicle on another DLE target lesion twice daily for 6 weeks. Delgocitinib cream 20 mg/g: Cream for topical application. Delgocitinib cream vehicle: The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.
Period Title: Overall Study
STARTED	27
Lesions Treated With Delgocitinib Cream	27
Lesions Treated With Delgocitinib Cream Vehicle	27
COMPLETED	26
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	All Randomised Subjects
Arm/Group Description	Randomised subjects received delgocitinib cream 20 mg/g on one DLE target lesion and delgocitinib cream vehicle on another DLE target lesion twice daily for 6 weeks. Delgocitinib cream 20 mg/g: Cream for topical application. Delgocitinib cream vehicle: The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.
Overall Participants	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.7 (13.4)
Sex: Female, Male (Count of Participants)
Female	15 55.6%
Male	12 44.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 7.4%
Not Hispanic or Latino	24 88.9%
Unknown or Not Reported	1 3.7%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	2 7.4%
White	20 74.1%
Other	4 14.8%
Unknown or Not Reported	1 3.7%
Region of Enrollment (participants) [Number]
United States	4 14.8%
Denmark	1 3.7%
France	5 18.5%
Germany	17 63%
Investigator's Global Assessment (IGA) of lesions to be treated with delgocitinib cream (percentage of lesions) [Number]
IGA score 3 (moderate)	88.9
IGA score 4 (severe)	11.1
Investigator's Global Assessment (IGA) of lesions to be treated with vehicle (percentage of lesions) [Number]
IGA score 3 (moderate)	88.9
IGA score 4 (severe)	11.1
Baseline erythema score of lesions to be treated with delgocitinib cream (percentage of lesions) [Number]
Erythema score 2	37.0
Erythema score 3	63.0
Baseline erythema score of lesions to be treated with vehicle (percentage of lesions) [Number]
Erythema score 2	48.1
Erythema score 3	51.9
Total skin disease activity score of lesions to be treated with delgocitinib cream (scores on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [scores on a scale]	5.0
Total skin disease activity score of lesions to be treated with vehicle (scores on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [scores on a scale]	5.0

Outcome Measures

1. Primary Outcome

Title	Target Lesions With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 6.
Description	The IGA is an instrument used in clinical trials to rate the severity of the subject's global disease and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). In this trial, the IGA was a lesion-specific assessment and was evaluated separately for each of the 2 target lesions.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Per protocol (PP) analysis set. 5 subjects were excluded from the per protocol (PP) analysis set as the primary endpoint data were compromised. The PP analysis set hence comprised 22 (81.5%) subjects. Data at Week 8 was excluded from the PP analysis set for 2 subjects, as they used prohibited concomitant medication in the safety follow-up period.

Arm/Group Title	Delgocitinib Cream 20 mg/g	Delgocitinib Cream Vehicle
Arm/Group Description	Delgocitinib cream applied twice daily for 6 weeks Delgocitinib cream: Cream for topical application.	Delgocitinib cream vehicle applied twice daily for 6 weeks Delgocitinib cream vehicle: The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.
Measure Participants	22	22
Number [lesions]	3	6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Delgocitinib Cream 20 mg/g, Delgocitinib Cream Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4531
	Comments	Exact p-value of McNemar's test.
	Method	McNemar
	Comments
Method of Estimation	Estimation Parameter	Attributable risk
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	Attributable risk is defined as the difference in estimated probability of treatment success of delgocitinib compared to vehicle. Exact p-value of McNemar's test. Success is defined as having an IGA score of 0 (clear) or 1 (almost clear) at Week 6.

2. Secondary Outcome

Title	Number of Adverse Events (AEs) up to Week 6.
Description	Number of AEs from baseline to Week 6
Time Frame	Week 0 to Week 6

Outcome Measure Data

Analysis Population Description

Safety analysis set. All 27 subjects were exposed to IMP. All subjects were treated with delgocitinib cream on one target lesion and with vehicle on another target lesion, and except for lesion-specific AEs, it was therefore not possible to distinguish between AEs related to delgocitinib cream or vehicle treatment.

Arm/Group Title	All Subjects
Arm/Group Description	All subjects received delgocitinib cream 20 mg/g on one DLE target lesion and delgocitinib cream vehicle on another DLE target lesion twice daily for 6 weeks. Delgocitinib cream 20 mg/g: Cream for topical application. Delgocitinib cream vehicle: The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.
Measure Participants	27
Number [AEs]	8

3. Secondary Outcome

Title	Number of Subjects With AEs up to Week 6.
Description	Number of subjects with AEs from baseline to Week 6
Time Frame	Week 0 to Week 6

Outcome Measure Data

Analysis Population Description

Safety analysis set. All 27 subjects were exposed to IMP. All subjects were treated with delgocitinib cream on one target lesion and with vehicle on another target lesion, and except for lesion-specific AEs, it was therefore not possible to distinguish between AEs related to delgocitinib cream or vehicle treatment.

Arm/Group Title	All Subjects
Arm/Group Description	All subjects received delgocitinib cream 20 mg/g on one DLE target lesion and delgocitinib cream vehicle on another DLE target lesion twice daily for 6 weeks. Delgocitinib cream 20 mg/g: Cream for topical application. Delgocitinib cream vehicle: The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.
Measure Participants	27
Count of Participants [Participants]	8 29.6%

4. Secondary Outcome

Title	Number of Lesion-specific, Treatment-related AEs up to Week 6.
Description	The number of lesion-specific, treatment-related AEs per target lesion will be compared for active and vehicle treatment. Lesion-specific AEs are defined as lesional/perilesional AEs (i.e. AE location within the treatment area and/or ≤2 cm from the border of a target lesion).
Time Frame	Week 0 to Week 6

Outcome Measure Data

Analysis Population Description

Safety analysis set. All 27 subjects were exposed to IMP. All subjects were treated with delgocitinib cream on one target lesion and with vehicle on another target lesion. It was therefore only possible to distinguish between AEs related to delgocitinib cream or vehicle treatment for the lesion-specific AEs.

Arm/Group Title	Delgocitinib Cream 20 mg/g	Delgocitinib Cream Vehicle
Arm/Group Description	Delgocitinib cream applied twice daily for 6 weeks Delgocitinib cream: Cream for topical application.	Delgocitinib cream vehicle applied twice daily for 6 weeks Delgocitinib cream vehicle: The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.
Measure Participants	27	27
Number [AEs]	2	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Delgocitinib Cream 20 mg/g, Delgocitinib Cream Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5000
	Comments	Exact p-value of McNemar's test.
	Method	McNemar
	Comments
Method of Estimation	Estimation Parameter	Attributable risk
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	Attributable risk is defined as the difference in estimated probability of treatment success (i.e. no lesion-specific treatment-related AEs) of delgocitinib compared to vehicle. Exact p-value of McNemar's test.

5. Secondary Outcome

Title	Number of Lesions With ≥2-point Reduction in IGA Score at Week 6 Compared to Baseline.
Description	The IGA is an instrument used in clinical trials to rate the severity of the subject's global disease and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). In this trial, the IGA was a lesion-specific assessment and was evaluated separately for each of the 2 target lesions.
Time Frame	Week 0 to Week 6

Outcome Measure Data

Analysis Population Description

Per protocol (PP) analysis set. 5 subjects were excluded from the per protocol (PP) analysis set as the primary endpoint data were compromised. The PP analysis set hence comprised 22 (81.5%) subjects. Data at Week 8 was excluded from the PP analysis set for 2 subjects, as they used prohibited concomitant medication in the safety follow-up period.

Arm/Group Title	Delgocitinib Cream 20 mg/g	Delgocitinib Cream Vehicle
Arm/Group Description	Delgocitinib cream applied twice daily for 6 weeks Delgocitinib cream: Cream for topical application.	Delgocitinib cream vehicle applied twice daily for 6 weeks Delgocitinib cream vehicle: The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.
Measure Participants	22	22
Number [lesions]	3	6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Delgocitinib Cream 20 mg/g, Delgocitinib Cream Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4531
	Comments	Exact p-value of McNemar's test.
	Method	McNemar
	Comments
Method of Estimation	Estimation Parameter	Attributable risk
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	Attributable risk is defined as the difference in estimated probability of treatment success of delgocitinib vs vehicle. Exact p-value of McNemar's test. Success is defined as having at least a 2-point reduction in IGA score from baseline to Week 6.

6. Secondary Outcome

Title	Number of Lesions With ≥2-point Reduction in Erythema Score at Week 6 Compared to Baseline.
Description	The erythema score is lesion-specific and based on the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the Revised CLASI (RCLASI) which are validated scoring systems to assess disease activity and damage in patients with cutaneous lupus erythematosus. The severity of the erythema is scored on a 4-point scale ranging from 0 to 3. The severity is scored from low to high with 0=absent and 3=dark red, purple/violaceous/crusted/haemorrhagic.
Time Frame	Week 0 to Week 6

Outcome Measure Data

Analysis Population Description

Per protocol (PP) analysis set. 5 subjects were excluded from the per protocol (PP) analysis set as the primary endpoint data were compromised. The PP analysis set hence comprised 22 (81.5%) subjects. Data at Week 8 was excluded from the PP analysis set for 2 subjects, as they used prohibited concomitant medication in the safety follow-up period.

Arm/Group Title	Delgocitinib Cream 20 mg/g	Delgocitinib Cream Vehicle
Arm/Group Description	Delgocitinib cream applied twice daily for 6 weeks Delgocitinib cream: Cream for topical application.	Delgocitinib cream vehicle applied twice daily for 6 weeks Delgocitinib cream vehicle: The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.
Measure Participants	22	22
Number [lesions]	5	5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Delgocitinib Cream 20 mg/g, Delgocitinib Cream Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	Exact p-value of McNemar's test.
	Method	McNemar
	Comments
Method of Estimation	Estimation Parameter	Attributable risk
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -0.22 to 0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Attributable risk is defined as the difference in estimated probability of treatment success of delgocitinib compared to vehicle. Exact p-value of McNemar's test. Success is defined as having at least a 2-point reduction in IGA score from baseline to Week 6.

7. Secondary Outcome

Title	Erythema Score at Week 6.
Description	The erythema score is lesion-specific and based on the CLASI and the RCLASI which are validated scoring systems to assess disease activity and damage in patients with cutaneous lupus erythematosus. The severity of the erythema is scored on a 4-point scale ranging from 0 to 3. The severity is scored from low to high with 0=absent and 3=dark red, purple/violaceous/crusted/haemorrhagic.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Per protocol (PP) analysis set.

Arm/Group Title	Delgocitinib Cream 20 mg/g	Delgocitinib Cream Vehicle
Arm/Group Description	Delgocitinib cream applied twice daily for 6 weeks Delgocitinib cream: Cream for topical application.	Delgocitinib cream vehicle applied twice daily for 6 weeks Delgocitinib cream vehicle: The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.
Measure Participants	22	22
Median (Inter-Quartile Range) [scores on a scale]	1.5	1.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Delgocitinib Cream 20 mg/g, Delgocitinib Cream Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5797
	Comments	P-value of the Wilcoxon signed rank test.
	Method	Wilcoxon signed rank test
	Comments	Erythema is scored as 0=absent, 1=pink, faint, 2=red, 3=dark red, purple/violaceous/crusted/haemorrhagic. P-value of the Wilcoxon signed rank test.

8. Secondary Outcome

Title	Total Skin Disease Activity Score (Sum of Scores for Erythema, Scaling/Hyperkeratosis, and Oedema/Infiltration) at Week 6.
Description	The skin disease activity scores are based on the CLASI and the RCLASI which are validated scoring systems to assess disease activity and damage in patients with cutaneous lupus erythematosus. The total skin disease activity score is defined as the sum of the scores for 3 clinical signs (erythema, scaling/hyperkeratosis, oedema/infiltration) for each target lesion. For the total score and the individual clinical signs, higher scores indicate more severe symptoms. Erythema is scored on a 4-point scale ranging from 0 (absent) to 3 (dark red, purple/violaceous/crusted/haemorrhagic). Hyperkeratosis/scaling is scored on a 3-point scale from 0 (absent) to 2 (verrucous hyperkeratosis). Oedema/infiltration is scored on a 3-point scale from 0 (absent) to 2 (palpable and visible). The total skin disease activity score can therefore range from 0 to 7.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Per protocol (PP) analysis set. 5 subjects were excluded from the per protocol (PP) analysis set as the primary endpoint data were compromised. The PP analysis set hence comprised 22 (81.5%) subjects. Data at Week 8 was excluded from the PP analysis set for 2 subjects, as they used prohibited concomitant medication in the safety follow-up period.

Arm/Group Title	Delgocitinib Cream 20 mg/g	Delgocitinib Cream Vehicle
Arm/Group Description	Delgocitinib cream applied twice daily for 6 weeks Delgocitinib cream: Cream for topical application.	Delgocitinib cream vehicle applied twice daily for 6 weeks Delgocitinib cream vehicle: The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.
Measure Participants	22	22
Median (Inter-Quartile Range) [scores on a scale]	2.5	2.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Delgocitinib Cream 20 mg/g, Delgocitinib Cream Vehicle
	Comments	Total skin disease activity score is the sum of the scores for erythema, scaling/hyperkeratosis, and oedema/infiltration. Total skin disease activity score ranges from 0 to 7 with lower score indicating better state.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7862
	Comments	P-value of the Wilcoxon signed rank test.
	Method	Wilcoxon signed rank test
	Comments	P-value of the Wilcoxon signed rank test.

Adverse Events

Time Frame	8 weeks
Adverse Event Reporting Description	All 27 subjects in the safety analysis set were treated with delgocitinib cream on one target lesion and with vehicle on another target lesion, and except for lesion-specific AEs, it was therefore not possible to distinguish between AEs related to delgocitinib cream or vehicle treatment.
Arm/Group Title	All Subjects
Arm/Group Description	All 27 subjects in the safety analysis set were treated with delgocitinib cream on one target lesion and with vehicle on another target lesion, and except for lesion-specific AEs, it was therefore not possible to distinguish between AEs related to delgocitinib cream or vehicle treatment. Delgocitinib cream 20 mg/g: Cream for topical application. Delgocitinib cream vehicle: The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.
All Cause Mortality
	All Subjects
	Affected / at Risk (%)	# Events
Total	0/27 (0%)
Serious Adverse Events
	All Subjects
	Affected / at Risk (%)	# Events
Total	0/27 (0%)
Other (Not Including Serious) Adverse Events
	All Subjects
	Affected / at Risk (%)	# Events
Total	10/27 (37%)
Ear and labyrinth disorders
Middle ear inflammation	1/27 (3.7%)	1
Gastrointestinal disorders
Gastrointestinal disorder	1/27 (3.7%)	1
General disorders
Application site pain	1/27 (3.7%)	2
Application site pruritus	1/27 (3.7%)	1
Infections and infestations
Nasopharyngitis	4/27 (14.8%)	5
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/27 (3.7%)	1
Nervous system disorders
Headache	1/27 (3.7%)	1
Skin and subcutaneous tissue disorders
Cutaneous lupus erythematosus	1/27 (3.7%)	1
Rash erythematous	1/27 (3.7%)	1

Limitations/Caveats

The trial was terminated prematurely due to slow recruitment, and due to an anticipation that recruitment would become further delayed due to the COVID-19 pandemic affecting recruitment activities. The total number of subjects included in the trial therefore ended with 27 subjects randomised. 26 subjects completed the trial, as 1 subject withdrew from the trial due to an AE (moderate cutaneous lupus erythematosus [CLE]; reported term: cutaneous lupus erythematosus flare).

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

LEO Pharma A/S seeks publication of all clinical trials in peer-reviewed journals within 18 months after completion or termination of the clinical trial, regardless of whether the findings are positive or negative. If no publication is submitted by LEO Pharma A/S within these 18 months, the investigator has the right to publish the results from the clinical trial generated by him/herself.