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Clinical Trial Results:
Open clinical study to assess long-term efficacy and safety of dimethyl fumarate in adults with moderate to severe chronic plaque psoriasis in real practice (DIMESKIN 1 Trial)

Summary
EudraCT number	2017-001368-40
Trial protocol	ES
Global end of trial date	02 Apr 2020

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

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

M-41008-41

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Almirall S.A.

Sponsor organisation address

Ronda General Mitre, 151, Barcelona, Spain, 08022

Public contact

David Asensio Torres, Almirall S.A., +34 932917506, david.asensio@almirall.com

Scientific contact

Dra. Meritxell Guilà, Almirall S.A., +34 932913074, txell.guila@almirall.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

07 Sep 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

02 Apr 2020

Was the trial ended prematurely?

Main objective of the trial

To assess the efficacy of dimethylfumarate (DMF) at treatment week 24 by reducing at least 75% in the Psoriasis Area and Severity Index (PASI75) compared to baseline in adults with moderate to severe chronic plaque psoriasis.

Protection of trial subjects

The present clinical trial was conducted in accordance with the protocol, the principles established in the revised version of the Declaration of Helsinki concerning medical research involving human subjects (64th General Assembly, Fortaleza, Brazil, 2013), and the International Conference on Harmonization (ICH) Tripartite Harmonized Standards for Good Clinical Practice 1996. It was also conducted in accordance with applicable regulatory requirements, in particular Royal Decree 1090/2015 and Regulation (EU) 536/2014, regulating clinical trials with medicinal products in Spain and the European Union, respectively, and Law 14/2007, concerning biomedical research. By signing the protocol, the investigators agreed to follow the instructions and procedures described therein and therefore to comply with the GCP principles on which it is based. The study began once CEIm and AEMPS approval was obtained. The informed consent of each subject was freely given prior to participation in the clinical trial, either in writing or orally in front of witnesses. The study personnel involved in the conduct of this trial were sufficiently qualified by education, training, and experience to perform their assigned tasks. This trial did not use the services of personnel who had been sanctioned/suspended for scientific fraud or clinical malpractice.

Background therapy

No other therapies, (other than the subject's usual treatments which do not fall in the non-inclusion criteria defined in the protocol), were administered in the framework of the study.

Evidence for comparator

This is a single arm, a non-comparative study carried out in real clinical situation.

Actual start date of recruitment

12 Sep 2017

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

1 Years

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 282

Worldwide total number of subjects

282

EEA total number of subjects

282

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

258

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Patient recruitment for the study was conducted between October 2017 and March 2019. A total of 300 patients were recruited in 36 Spanish centers, of which 18 were considered a selection failure.

Screening details

Patients recruited in the study had a moderate to severe psoriasis (defined as PASI ≥ 10 or BSA ≥ 10 and PASI ≥ 5 or DLQI ≥ 10 and PASI ≥ 5), a diagnosis of chronic plaque psoriasis at least 6 months before, a good and stable medical condition for the clinical trial conduction, and were suitable subjects for systemic treatment of psoriasis.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

DMF (Skilarence)

Arm description

The patients included in the clinical trial received Dimethyl fumarate (DMF) as stated in the datasheet, with gradual dose increments during the first 9 weeks.

Arm type

Experimental

Investigational medicinal product name

Dimethyl fumarate (DMF)

Investigational medicinal product code

624-49-7

Other name

Skilarance

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Each gastro-resistant tablet contains 30 mg or 120g of DMF, and 34.2 and 136.8 mg of lactose as excipient, respectively. In the first week patients took one 30 mg DMF tablet once a day; in the second week one 30 mg DMF tablet twice a day; and in the third week of treatment one 30 mg DMF tablet three times a day. They switched to one 120 mg DMF tablet once a day in the fourth week of treatment. After that, the dose was increased by one 120 mg DMF tablet per week for the next 5 weeks, reaching a maximum dose of 720 mg per day.

Number of subjects in period 1	DMF (Skilarence)
Started	282
Week 24	169
Completed	77
Not completed	205
Adverse event, serious fatal	1
Consent withdrawn by subject	48
Physician decision	7
Adverse event, non-fatal	104
More than 7 days without follow-up	1
Patient's decision	4
Lost to follow-up	11
Protocol deviation	17
Lack of efficacy	12

Baseline characteristics

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Reporting group title

Overall trial

Reporting group description

Patients who took at least one dose of study medication. It is also the safety population.

Reporting group values	Overall trial	Total
Number of subjects	282	282
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	258	258
From 65-84 years	24	24
85 years and over	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	46.5 ± 13.0	-
Gender categorical
Units: Subjects
Female	97	97
Male	185	185
Race
Units: Subjects
Caucasian	271	271
Asian	3	3
Arab	4	4
Hispanic	4	4
Type of psoriasis at diagnosis
Units: Subjects
Plaque psoriasis	274	274
Guttate psoriasis	6	6
Pustular psoriasis	2	2
Last previous treatment received
Units: Subjects
Topical + systemic + phototherapy	75	75
Topical + systemic	69	69
Topical + phototherapy	36	36
Systemic + phototherapy	5	5
Topical	73	73
Systemic	9	9
Phototherapy	2	2
None	13	13
Last previous topical and systemic treatment
Units: Subjects
Acitretin	6	6
Acitretin + Corticosteroids + D vitamin analogues	1	1
D vitamin analogues	4	4
Cyclosporine	15	15
Cyclosporine +Corticosteroids +D vitamin analogues	2	2
Corticosteroids	33	33
Corticosteroids + A vitamin analogues	1	1
Corticosteroids+A vitamin analogues+salicylic acid	1	1
Corticosteroids + D vitamin analogues	124	124
Corticosteroids + D vitamin analogues + Ebastina	1	1
Corticosteroids+D vitamin analogues+Other topicals	7	7
Corticosteroids+D vitamin analogues+Salicylic acid	13	13
CS+D vitamin anologues+Salicylic acid+Gentamicin	1	1
Corticosteroids + Pimecrolimus	2	2
Corticosteroids + Salicylic acid	4	4
Difur	1	1
Emollients	1	1
Methotrexate	27	27
Methotrexate + Corticosteroids	2	2
Methotrexate +Corticosteroids +D vitamin analogues	8	8
Methotrexate+CS+D vitamin anologues+Other topicals	2	2
Methotrexate+CS+D vitamin anologues+Salicylic acid	1	1
Methotrexate + Salicylic acid	1	1
Other unknown topical treatment	1	1
Prednisone	2	2
Salicylic acid formulations	3	3
None	15	15
Not available	3	3
Last previous phototherapy received
Units: Subjects
PUVA + UVB	16	16
PUVA	22	22
UVB	80	80
None	161	161
Not available	3	3
Baseline PGA
There is one patient with no information on PGA at screening, baseline, or subsequent visits.
Units: Subjects
Mild	12	12
Moderate	193	193
Moderate-severe	72	72
Severe	4	4
Not available	1	1
Body mass index (BMI)
Units: Kg/m2
arithmetic mean (standard deviation)	27.9 ± 4.9	-
Time since diagnosis
Units: Years
arithmetic mean (standard deviation)	18.1 ± 13.5	-
Number of relapses in the previous year
Units: number
arithmetic mean (standard deviation)	2.1 ± 2.5	-
No. of visits to dermatologist in the last 6 months
Units: number
arithmetic mean (standard deviation)	2.4 ± 1.4	-
Weight
Units: Kg
arithmetic mean (standard deviation)	80.2 ± 16.0	-
Height
Units: meters
arithmetic mean (standard deviation)	1.7 ± 0.1	-
Number of systemic treatments per patient
Units: number
arithmetic mean (standard deviation)	1.4 ± 2.0	-
No. of different systemic treatments per patient
The "other" category has been counted as a single different treatment.
Units: number
arithmetic mean (standard deviation)	0.9 ± 1.0	-
Baseline PASI
In 2 patients, without baseline PASI, the information was completed with the screening visit.
Units: Score
arithmetic mean (standard deviation)	13.3 ± 5.7	-
Baseline BSA
One patient has not indicated a BSA value at either the baseline or screening visit, but has information available at subsequent visits.
Units: Score
arithmetic mean (standard deviation)	17.4 ± 11.8	-
Baseline DLQI
Units: Score
arithmetic mean (standard deviation)	12.2 ± 7.3	-
Baseline pruritus EVA
Units: Score
arithmetic mean (standard deviation)	6.9 ± 2.4	-

Subject analysis set title

DMF (ITTm)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Those patients who took the medication and had at least one PASI measurement after the baseline visit.

Subject analysis set title

DMF (ITT)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Those patients who met the selection criteria, took the medication and had at least one PASI measurement after the baseline visit.

Subject analysis set title

DMF (PP)

Subject analysis set type

Per protocol

Subject analysis set description

Those patients who took the corresponding medication and for whom all the requested information was available without significant deviations from the protocol.

Subject analysis set title

Statistical analysis

Subject analysis set type

Sub-group analysis

Subject analysis set description

This is a single-arm study. Unfortunately, this EudraCT form cannot accommodate for this type of study. Hence, this subgroup has been artificially created for statistical analysis in some endpoints.

Subject analysis sets values	DMF (ITTm)	DMF (ITT)	DMF (PP)	Statistical analysis
Number of subjects	274	264	156	1
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)	250
From 65-84 years	24
85 years and over	0
Age continuous
Units: years
arithmetic mean (standard deviation)	46.6 ± 13.0	±	±	±
Gender categorical
Units: Subjects
Female	93
Male	181
Race
Units: Subjects
Caucasian	263
Asian	3
Arab	4
Hispanic	4
Type of psoriasis at diagnosis
Units: Subjects
Plaque psoriasis	266
Guttate psoriasis	6
Pustular psoriasis	2
Last previous treatment received
Units: Subjects
Topical + systemic + phototherapy	73
Topical + systemic	69
Topical + phototherapy	34
Systemic + phototherapy	4
Topical	70
Systemic	9
Phototherapy	2
None	13
Last previous topical and systemic treatment
Units: Subjects
Acitretin	6
Acitretin + Corticosteroids + D vitamin analogues	1
D vitamin analogues	4
Cyclosporine	14
Cyclosporine +Corticosteroids +D vitamin analogues	2
Corticosteroids	30
Corticosteroids + A vitamin analogues	1
Corticosteroids+A vitamin analogues+salicylic acid	1
Corticosteroids + D vitamin analogues	121
Corticosteroids + D vitamin analogues + Ebastina	1
Corticosteroids+D vitamin analogues+Other topicals	7
Corticosteroids+D vitamin analogues+Salicylic acid	13
CS+D vitamin anologues+Salicylic acid+Gentamicin	1
Corticosteroids + Pimecrolimus	2
Corticosteroids + Salicylic acid	4
Difur	1
Emollients	1
Methotrexate	27
Methotrexate + Corticosteroids	2
Methotrexate +Corticosteroids +D vitamin analogues	8
Methotrexate+CS+D vitamin anologues+Other topicals	2
Methotrexate+CS+D vitamin anologues+Salicylic acid	1
Methotrexate + Salicylic acid	1
Other unknown topical treatment	1
Prednisone	2
Salicylic acid formulations	2
None	15
Not available	3
Last previous phototherapy received
Units: Subjects
PUVA + UVB	14
PUVA	21
UVB	78
None	158
Not available	3
Baseline PGA
There is one patient with no information on PGA at screening, baseline, or subsequent visits.
Units: Subjects
Mild	11
Moderate	188
Moderate-severe	70
Severe	4
Not available	1
Body mass index (BMI)
Units: Kg/m2
arithmetic mean (standard deviation)	27.9 ± 4.8	±	±	±
Time since diagnosis
Units: Years
arithmetic mean (standard deviation)	18.2 ± 13.6	±	±	±
Number of relapses in the previous year
Units: number
arithmetic mean (standard deviation)	2.1 ± 2.5	±	±	±
No. of visits to dermatologist in the last 6 months
Units: number
arithmetic mean (standard deviation)	2.4 ± 1.5	±	±	±
Weight
Units: Kg
arithmetic mean (standard deviation)	80.3 ± 16.0	±	±	±
Height
Units: meters
arithmetic mean (standard deviation)	1.7 ± 0.1	±	±	±
Number of systemic treatments per patient
Units: number
arithmetic mean (standard deviation)	2.6 ± 2.1	±	±	±
No. of different systemic treatments per patient
The "other" category has been counted as a single different treatment.
Units: number
arithmetic mean (standard deviation)	1.6 ± 0.7	±	±	±
Baseline PASI
In 2 patients, without baseline PASI, the information was completed with the screening visit.
Units: Score
arithmetic mean (standard deviation)	13.3 ± 5.8	±	±	±
Baseline BSA
One patient has not indicated a BSA value at either the baseline or screening visit, but has information available at subsequent visits.
Units: Score
arithmetic mean (standard deviation)	17.4 ± 11.9	±	±	±
Baseline DLQI
Units: Score
arithmetic mean (standard deviation)	12.3 ± 7.3	±	±	±
Baseline pruritus EVA
Units: Score
arithmetic mean (standard deviation)	6.9 ± 2.4	±	±	±

End points

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Reporting group title

DMF (Skilarence)

Reporting group description

The patients included in the clinical trial received Dimethyl fumarate (DMF) as stated in the datasheet, with gradual dose increments during the first 9 weeks.

Subject analysis set title

DMF (ITTm)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Those patients who took the medication and had at least one PASI measurement after the baseline visit.

Subject analysis set title

DMF (ITT)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Those patients who met the selection criteria, took the medication and had at least one PASI measurement after the baseline visit.

Subject analysis set title

DMF (PP)

Subject analysis set type

Per protocol

Subject analysis set description

Those patients who took the corresponding medication and for whom all the requested information was available without significant deviations from the protocol.

Subject analysis set title

Statistical analysis

Subject analysis set type

Sub-group analysis

Subject analysis set description

This is a single-arm study. Unfortunately, this EudraCT form cannot accommodate for this type of study. Hence, this subgroup has been artificially created for statistical analysis in some endpoints.

Primary: Number of subjects who achieved PASI75 response at Week 24 (ADO)

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End point title

Number of subjects who achieved PASI75 response at Week 24 (ADO) ^[1]

End point description

The primary endpoint of the study was the number of patients achieving a reduction ≥ 75% in PASI compared to baseline (PASI75) at week 24 of DMF treatment. PASI is a scoring method for the assessment and classification of patient psoriasis severity. PASI combines the assessment of each psoriasis lesion from 0 to 4 (0=none, 1=mild, 2=moderate, 3=marked, 4=very marked) based on three parameters: erythema, infiltration and desquamation, as well as a weighted assessment of the area affected divided into body parts (head, trunk, upper extremities and lower extremities). The PASI ranges between 0 and 72. Analysis carried out with available data only (ADO). The "number of subjects analyzed" means subjects analyzed for this endpoint.

End point type

Primary

End point timeframe

From baseline up to Week 24 of treatment.

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This is a single-arm study. No comparative analyses were planned for this endpoint (only descriptive statistics).

End point values	DMF (ITTm)	DMF (ITT)	DMF (PP)
Number of subjects analysed	162	156	156
Units: subjects	96	93	93

No statistical analyses for this end point

Primary: Number of subjects who achieved PASI75 response at Week 24 (LOCF)

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End point title

Number of subjects who achieved PASI75 response at Week 24 (LOCF) ^[2]

End point description

The primary endpoint of the study was the number of patients achieving a reduction ≥ 75% in PASI compared to baseline (PASI75) at week 24 of DMF treatment. PASI is a scoring method for the assessment and classification of patient psoriasis severity. PASI combines the assessment of each psoriasis lesion from 0 to 4 (0=none, 1=mild, 2=moderate, 3=marked, 4=very marked) based on three parameters: erythema, infiltration and desquamation, as well as a weighted assessment of the area affected divided into body parts (head, trunk, upper extremities and lower extremities). The PASI ranges between 0 and 72. Data analyzed with Last Observation Carried Forward (LOCF) method. The "number of subjects analyzed" means subjects analyzed for this endpoint.

End point type

Primary

End point timeframe

From baseline up to Week 24 of treatment.

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This is a single-arm study. No comparative analyses were planned for this endpoint (only descriptive statistics).

End point values	DMF (ITTm)	DMF (ITT)	DMF (PP)
Number of subjects analysed	274	264	156
Units: subjects	108	104	93

No statistical analyses for this end point

Primary: Number of subjects who achieved PASI75 response at Week 24 (MI)

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End point title

Number of subjects who achieved PASI75 response at Week 24 (MI) ^[3]

End point description

The primary endpoint of the study was the number of patients achieving a reduction ≥ 75% in PASI compared to baseline (PASI75) at week 24 of DMF treatment. PASI is a scoring method for the assessment and classification of patient psoriasis severity. PASI combines the assessment of each psoriasis lesion from 0 to 4 (0=none, 1=mild, 2=moderate, 3=marked, 4=very marked) based on three parameters: erythema, infiltration and desquamation, as well as a weighted assessment of the area affected divided into body parts (head, trunk, upper extremities and lower extremities). The PASI ranges between 0 and 72. Data analyzed with Multiple Imputation (MI) method. The "number of subjects analyzed" means subjects analyzed for this endpoint.

End point type

Primary

End point timeframe

From baseline up to Week 24 of treatment.

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This is a single-arm study. No comparative analyses were planned for this endpoint (only descriptive statistics).

End point values	DMF (ITTm)	DMF (ITT)	DMF (PP)
Number of subjects analysed	274	264	156
Units: subjects	126	121	93

No statistical analyses for this end point

Secondary: Number of subjects who achieved PASI75 response over 52 weeks

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End point title

Number of subjects who achieved PASI75 response over 52 weeks

End point description

This secondary endpoint of the study was the number of patients achieving a reduction ≥ 75% in PASI compared to baseline (PASI75) at weeks 4, 8, 12, 24, 36, 48, and 52 of DMF treatment. Analysis carried out with available data only (ADO). Here, ‘n’= subjects analyzed for this endpoint for specified rows (time points). No comparative statistical analysis was performed, only descriptive statistics.

End point type

Secondary

End point timeframe

From baseline up to Weeks 4, 8, 12, 24, 36, 48, and 52 of treatment.

End point values	DMF (ITTm)
Number of subjects analysed	274 ^[4]
Units: subjects
Week 4 (n=270)	3
Week 8 (n=244)	27
Week 12 (n=203)	72
Week 24 (n=162)	96
Week 36 (n=121)	94
Week 48 (n=95)	73
Week 52 (n=77)	61

Notes
[4] - Number of subjects at baseline. The number of subjects analyzed at each time point is shown below.

No statistical analyses for this end point

Secondary: Number of subjects who achieved PASI50 response over 52 weeks

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End point title

Number of subjects who achieved PASI50 response over 52 weeks

End point description

This secondary endpoint of the study was the number of patients achieving a reduction ≥ 50% in PASI compared to baseline (PASI50) at weeks 4, 8, 12, 24, 36, 48, and 52 of DMF treatment. Analysis carried out with available data only (ADO). Here, ‘n’= subjects analyzed for this endpoint for specified rows (time points). No comparative statistical analysis was performed, only descriptive statistics.

End point type

Secondary

End point timeframe

From baseline up to Weeks 4, 8, 12, 24, 36, 48, and 52 of treatment.

End point values	DMF (ITTm)
Number of subjects analysed	274 ^[5]
Units: subjects
Week 4 (n=270)	39
Week 8 (n=244)	96
Week 12 (n=203)	128
Week 24 (n=162)	133
Week 36 (n=121)	109
Week 48 (n=95)	84
Week 52 (n=77)	71

Notes
[5] - Number of subjects at baseline. The number of subjects analyzed at each time point is shown below.

No statistical analyses for this end point

Secondary: Number of subjects who achieved PASI90 response over 52 weeks

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End point title

Number of subjects who achieved PASI90 response over 52 weeks

End point description

This secondary endpoint of the study was the number of patients achieving a reduction ≥ 90% in PASI compared to baseline (PASI90) at weeks 4, 8, 12, 24, 36, 48, and 52 of DMF treatment. Analysis carried out with available data only (ADO). Here, ‘n’= subjects analyzed for this endpoint for specified rows (time points). No comparative statistical analysis was performed, only descriptive statistics.

End point type

Secondary

End point timeframe

From baseline up to Weeks 4, 8, 12, 24, 36, 48, and 52 of treatment.

End point values	DMF (ITTm)
Number of subjects analysed	274 ^[6]
Units: subjects
Week 4 (n=270)	0
Week 8 (n=244)	8
Week 12 (n=203)	27
Week 24 (n=162)	59
Week 36 (n=121)	61
Week 48 (n=95)	42
Week 52 (n=77)	36

Notes
[6] - Number of subjects at baseline. The number of subjects analyzed at each time point is shown below.

No statistical analyses for this end point

Secondary: Number of subjects who achieved PASI100 response over 52 weeks

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End point title

Number of subjects who achieved PASI100 response over 52 weeks

End point description

This secondary endpoint of the study was the number of patients achieving a reduction ≥ 100% in PASI compared to baseline (PASI100) at weeks 4, 8, 12, 24, 36, 48, and 52 of DMF treatment. Analysis carried out with available data only (ADO). Here, ‘n’= subjects analyzed for this endpoint for specified rows (time points). No comparative statistical analysis was performed, only descriptive statistics.

End point type

Secondary

End point timeframe

From baseline up to Weeks 4, 8, 12, 24, 36, 48, and 52 of treatment.

End point values	DMF (ITTm)
Number of subjects analysed	274 ^[7]
Units: subjects
Week 4 (n=270)	0
Week 8 (n=244)	1
Week 12 (n=203)	11
Week 24 (n=162)	30
Week 36 (n=121)	34
Week 48 (n=95)	24
Week 52 (n=77)	27

Notes
[7] - Number of subjects at baseline. The number of subjects analyzed at each time point is shown below.

No statistical analyses for this end point

Secondary: Change in PASI score over 52 weeks

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End point title

Change in PASI score over 52 weeks

End point description

Change in the mean ± SD of the PASI score (score change) during 52 weeks. PASI is a scoring method for the assessment and classification of patient psoriasis severity. PASI combines the assessment of each psoriasis lesion from 0 to 4 (0=none, 1=mild, 2=moderate, 3=marked, 4=very marked) based on three parameters: erythema, infiltration and desquamation, as well as a weighted assessment of the area affected divided into body parts (head, trunk, upper extremities and lower extremities). The PASI ranges between 0 and 72. Analysis carried out with available data only (ADO). Here, ‘n’= subjects analyzed for this endpoint for specified rows (time points).

End point type

Secondary

End point timeframe

From baseline up to Weeks 4, 8, 12, 24, 36, 48, and 52 of treatment.

End point values	DMF (ITTm)	Statistical analysis
Number of subjects analysed	76 ^[8]	1 ^[9]
Units: Score
arithmetic mean (standard deviation)
Baseline (n=274)	13.3 ± 5.8	0 ± 0
Week 4 (n=270)	10.3 ± 5.2	0 ± 0
Week 8 (n=244)	8.4 ± 5.3	0 ± 0
Week 12 (n=203)	5.7 ± 4.6	0 ± 0
Week 24 (n=162)	3.5 ± 4.2	0 ± 0
Week 36 (n=121)	2.5 ± 3.6	0 ± 0
Week 48 (n=95)	2.4 ± 3.4	0 ± 0
Week 52 (n=77)	2.2 ± 3.1	0 ± 0

Notes
[8] - Number of patients used for Wilcoxon signed-rank test with data from baseline to week 52 (N=77).
[9] - This form cannot cater for single-arm study. So, this subgroup was artificially set up for analysis.

Change in PASI score over 52 weeks

Statistical analysis description

Change in the mean ± SD of the PASI score from baseline up to Week 52.

Comparison groups

DMF (ITTm) v Statistical analysis

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[10]

P-value

< 0.001 ^[11]

Method

Wilcoxon signed-rank test

Confidence interval

Notes
[10] - This form is not suitable for single-arm clinical trials and does not allow statistical analysis of paired data from two observations at different time points for the same population. Therefore, the "statistical analysis" subgroup had to be artificially created to analyze the statistical significance of change score from baseline up to Week 52 by Wilcoxon signed-rank test.
[11] - There was a significant improvement in PASI score at Week 52 from Baseline.

Secondary: Number of subjects who achieved a PGA 0 response over 52 weeks

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End point title

Number of subjects who achieved a PGA 0 response over 52 weeks

End point description

Number of patients achieving a PGA = 0 at baseline and Weeks 4, 8, 12, 24, 36, 48, and 52 of treatment. The PGA score provides a subjective assessment of the severity of the disease and evaluates the intensity, but not the extent or symptomatology of the lesions. PGA uses a score between 0 and 5 (0=blank [no signs of psoriasis, post-inflammatory hyperpigmentation may be present]; 1=almost mild [intermediate between slight and mild]; 2=mild [mild elevation of plaque, scaling and/or erythema]; 3=moderate [moderate elevation of plaque, scaling and/or erythema]; 4=moderate-severe [marked elevation of plaque, scaling and/or erythema]; 5=severe [very marked elevation of plaque, scaling and/or erythema]). Analysis carried out with available data only (ADO). Here, ‘n’= subjects analyzed for this endpoint for specified rows (time points).

End point type

Secondary

End point timeframe

From baseline up to Weeks 4, 8, 12, 24, 36, 48, and 52 of treatment.

End point values	DMF (ITTm)	Statistical analysis
Number of subjects analysed	74 ^[12]	1 ^[13]
Units: subjects
Baseline (n=273)	0	0
Week 4 (n=269)	0	0
Week 8 (n=241)	2	0
Week 12 (n=201)	13	0
Week 24 (n=162)	31	0
Week 36 (n=121)	36	0
Week 48 (n=93)	31	0
Week 52 (n=75)	31	0

Notes
[12] - Number of patients used for Chi-Square test with data from baseline to week 52 (N=75).
[13] - This form cannot cater for single-arm study. So, this subgroup was artificially set up for analysis.

Change in subjects' percentage achieving a PGA = 0

Statistical analysis description

Change in the percentage of subjects achieving a PGA score of 0 (blank) from baseline up to Week 52 of treatment.

Comparison groups

DMF (ITTm) v Statistical analysis

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[14]

P-value

< 0.001 ^[15]

Method

Chi-squared

Confidence interval

Notes
[14] - This form is not suitable for single-arm clinical trials and does not allow statistical analysis of paired data from two observations at different time points for the same population. Therefore, the "statistical analysis" subgroup had to be artificially created to analyze the statistical significance of change score from baseline up to Week 52 by Chi-Square test.
[15] - There was a significant increase in subjects' percentage achieving a PGA score of 0 at Week 52 from Baseline.

Secondary: Number of subjects who achieved a PGA 1 response over 52 weeks

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End point title

Number of subjects who achieved a PGA 1 response over 52 weeks

End point description

Number of subjects achieving a PGA = 1 at baseline and Weeks 4, 8, 12, 24, 36, 48, and 52 of treatment. The PGA score provides a subjective assessment of the severity of the disease and evaluates the intensity, but not the extent or symptomatology of the lesions. PGA uses a score between 0 and 5 (0=blank [no signs of psoriasis, post-inflammatory hyperpigmentation may be present]; 1=almost mild [intermediate between slight and mild]; 2=mild [mild elevation of plaque, scaling and/or erythema]; 3=moderate [moderate elevation of plaque, scaling and/or erythema]; 4=moderate-severe [marked elevation of plaque, scaling and/or erythema]; 5=severe [very marked elevation of plaque, scaling and/or erythema]). Analysis carried out with available data only (ADO). Here, ‘n’= subjects analyzed for this endpoint for specified rows (time points).

End point type

Secondary

End point timeframe

From baseline up to Weeks 4, 8, 12, 24, 36, 48, and 52 of treatment.

End point values	DMF (ITTm)	Statistical analysis
Number of subjects analysed	74 ^[16]	1 ^[17]
Units: subjects
Baseline (n=273)	0	0
Week 4 (n=269)	8	0
Week 8 (n=241)	23	0
Week 12 (n=201)	52	0
Week 24 (n=162)	62	0
Week 36 (n=121)	51	0
Week 48 (n=93)	40	0
Week 52 (n=75)	29	0

Notes
[16] - Number of patients used for Chi-Square test with data from baseline to week 52 (N=75).
[17] - This form cannot cater for single-arm study. So, this subgroup was artificially set up for analysis.

Change in subjects' percentage achieving a PGA = 1

Statistical analysis description

Change in the percentage of subjects achieving a PGA score of 1 (almost blank) from baseline up to Week 52 of treatment.

Comparison groups

DMF (ITTm) v Statistical analysis

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[18]

P-value

< 0.001 ^[19]

Method

Chi-squared

Confidence interval

Notes
[18] - This form is not suitable for single-arm clinical trials and does not allow statistical analysis of paired data from two observations at different time points for the same population. Therefore, the "statistical analysis" subgroup had to be artificially created to analyze the statistical significance of change score from baseline up to Week 52 by Chi-Square test.
[19] - There was a significant increase in subjects' percentage achieving a PGA score of 1 at Week 52 from baseline.

Secondary: Change in BSA score over 52 weeks

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End point title

Change in BSA score over 52 weeks

End point description

Change in the mean ± SD of the BSA score (score change) during 52 weeks. The BSA measures the surface area affected by psoriasis lesions using the palm of the patient's hand (including fingers), as equivalent to 1% of the patient's total body surface area. Psoriasis is considered mild when it affects less than 3% of the skin surface, moderate when it affects between 3 and 8%, and severe when it affects more than 10%. Analysis carried out with available data only (ADO). Here, ‘n’= subjects analyzed for this endpoint for specified rows (time points).

End point type

Secondary

End point timeframe

From baseline up to Weeks 4, 8, 12, 24, 36, 48, and 52 of treatment.

End point values	DMF (ITTm)	Statistical analysis
Number of subjects analysed	76 ^[20]	1 ^[21]
Units: Score
arithmetic mean (standard deviation)
Baseline (n=273)	17.4 ± 11.9	0 ± 0
Week 4 (n=268)	15.0 ± 10.2	0 ± 0
Week 8 (n=243)	12.7 ± 9.9	0 ± 0
Week 12 (n=202)	9.7 ± 9.9	0 ± 0
Week 24 (n=161)	5.1 ± 8.0	0 ± 0
Week 36 (n=121)	3.2 ± 4.6	0 ± 0
Week 48 (n=95)	2.6 ± 4.2	0 ± 0
Week 52 (n=77)	2.8 ± 5.5	0 ± 0

Notes
[20] - Number of patients used for Wilcoxon signed-rank test with data from baseline to week 52 (N=77).
[21] - This form cannot cater for single-arm study. So, this subgroup was artificially set up for analysis.

Change in BSA score over 52 weeks

Statistical analysis description

Change in the mean ± SD of the BSA score from baseline up to Week 52.

Comparison groups

DMF (ITTm) v Statistical analysis

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[22]

P-value

< 0.001 ^[23]

Method

Wilcoxon signed-rank test

Confidence interval

Notes
[22] - This form is not suitable for single-arm clinical trials and does not allow statistical analysis of paired data from two observations at different time points for the same population. Therefore, the "statistical analysis" subgroup had to be artificially created to analyze the statistical significance of change score from baseline up to Week 52 by Wilcoxon signed-rank test.
[23] - There was a significant improvement in BSA score at Week 52 from Baseline.

Secondary: Change in EVA score of pruritus over 52 weeks

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End point title

Change in EVA score of pruritus over 52 weeks

End point description

Change in the mean ± SD of the EVA score of pruritus (score change) during 52 weeks. It is a single-item scale for the evaluation of the degree of itching, delimited by the terms "no itching" at point 0 and the term "unbearable itching" at the end of the scale. Analysis carried out with available data only (ADO). Here, ‘n’= subjects analyzed for this endpoint for specified rows (time points).

End point type

Secondary

End point timeframe

From baseline up to Weeks 4, 8, 12, 24, 36, 48, and 52 of treatment.

End point values	DMF (ITTm)	Statistical analysis
Number of subjects analysed	76 ^[24]	1 ^[25]
Units: Score
arithmetic mean (standard deviation)
Baseline (n=274)	6.9 ± 2.4	0 ± 0
Week 4 (n=270)	5.9 ± 2.5	0 ± 0
Week 8 (n=242)	5.2 ± 2.8	0 ± 0
Week 12 (n=203)	3.7 ± 2.6	0 ± 0
Week 24 (n=161)	2.8 ± 2.9	0 ± 0
Week 36 (n=118)	2.5 ± 2.9	0 ± 0
Week 48 (n=93)	2.2 ± 2.8	0 ± 0
Week 52 (n=77)	2.1 ± 2.6	0 ± 0

Notes
[24] - Number of patients used for Wilcoxon signed-rank test with data from baseline to week 52 (N=77).
[25] - This form cannot cater for single-arm study. So, this subgroup was artificially set up for analysis

Change in EVA score of pruritus over 52 weeks

Statistical analysis description

Change in the mean ± SD of the EVA score of pruritus from baseline up to Week 52.

Comparison groups

Statistical analysis v DMF (ITTm)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[26]

P-value

< 0.001 ^[27]

Method

Wilcoxon signed-rank test

Confidence interval

Notes
[26] - This form is not suitable for single-arm clinical trials and does not allow statistical analysis of paired data from two observations at different time points for the same population. Therefore, the "statistical analysis" subgroup had to be artificially created to analyze the statistical significance of change score from baseline up to Week 52 by Wilcoxon signed-rank test.
[27] - There was a significant improvement in EVA score of pruritus at Week 52 from Baseline.

Secondary: Change in DLQI score over 52 weeks

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End point title

Change in DLQI score over 52 weeks

End point description

Change in the mean ± SD of the DLQI score (score change) during 52 weeks. It is a dermatology-specific health-related quality of life (HRQoL) assessment tool developed to evaluate the impact of a dermatological disease on the patient's daily life. Analysis carried out with available data only (ADO). Here, ‘n’= subjects analyzed for this endpoint for specified rows (time points).

End point type

Secondary

End point timeframe

From baseline up to Weeks 4, 8, 12, 24, 36, 48, and 52 of treatment.

End point values	DMF (ITTm)	Statistical analysis
Number of subjects analysed	76 ^[28]	1 ^[29]
Units: score
arithmetic mean (standard deviation)
Baseline (n=274)	12.3 ± 7.3	0 ± 0
Week 4 (n=271)	9.5 ± 7.0	0 ± 0
Week 8 (n=243)	8.0 ± 7.0	0 ± 0
Week 12 (n=203)	5.8 ± 5.9	0 ± 0
Week 24 (n=161)	3.5 ± 5.0	0 ± 0
Week 36 (n=119)	2.5 ± 3.8	0 ± 0
Week 48 (n=94)	2.3 ± 4.2	0 ± 0
Week 52 (n=77)	1.9 ± 3.0	0 ± 0

Notes
[28] - Number of patients used for Wilcoxon signed-rank test with data from baseline to week 52 (N=77).
[29] - This form cannot cater for single-arm study. So, this subgroup was artificially set up for analysis.

Change in DLQI score over 52 weeks

Statistical analysis description

Change in the mean ± SD of the EVA score of pruritus from baseline up to Week 52.

Comparison groups

Statistical analysis v DMF (ITTm)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[30]

P-value

< 0.001 ^[31]

Method

Wilcoxon signed-rank test

Confidence interval

Notes
[30] - This form is not suitable for single-arm clinical trials and does not allow statistical analysis of paired data from two observations at different time points for the same population. Therefore, the "statistical analysis" subgroup had to be artificially created to analyze the statistical significance of change score from baseline up to Week 52 by Wilcoxon signed-rank test.
[31] - There was a significant improvement in DLQI score of pruritus at Week 52 from Baseline.

Secondary: Change in the satisfaction EVA score from Week 24 up to 52 or the discontinuation week

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End point title

Change in the satisfaction EVA score from Week 24 up to 52 or the discontinuation week

End point description

Change in the mean ± SD of the satisfaction EVA score (score change) during 52 weeks. It is a single-item scale for the evaluation of the degree of satisfaction with the treatment, delimited by the terms "completely unsatisfactory" for the score 0 and "completely satisfactory" for the score 10 of the scale. Analysis carried out with available data only (ADO). Here, ‘n’= subjects analyzed for this endpoint for specified rows (time points).

End point type

Secondary

End point timeframe

From Week 24 up to Week 52 or discontinuation week.

End point values	DMF (ITTm)	Statistical analysis
Number of subjects analysed	73 ^[32]	1 ^[33]
Units: score
arithmetic mean (standard deviation)
Week 24	7.6 ± 2.7	0 ± 0
Week of discontinuation	3.4 ± 3.4	0 ± 0
Week 52	8.4 ± 2.1	0 ± 0

Notes
[32] - Number of patients used for Wilcoxon signed-rank test with data from baseline to week 52 (N=74).
[33] - This form cannot cater for single-arm study. So, this subgroup was artificially set up for analysis

Change in the satisfaction EVA score

Statistical analysis description

Change in the mean ± SD of the satisfaction EVA score from Week 24 to Week 52 of treatment.

Comparison groups

DMF (ITTm) v Statistical analysis

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[34]

P-value

= 0.191 ^[35]

Method

Wilcoxon signed-rank test

Confidence interval

Notes
[34] - This form is not suitable for single-arm clinical trials and does not allow statistical analysis of paired data from two observations at different time points for the same population. Therefore, the "statistical analysis" subgroup had to be artificially created to analyze the statistical significance of change score from Week 24 to Week 52 by Wilcoxon signed-rank test.
[35] - Not statistically significant.

Adverse events

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Timeframe for reporting adverse events

From Baseline to Week 52.

Adverse event reporting additional description

AEs were obtained by asking patients neutral questions during visits and/or by collecting AEs spontaneously reported by the patient to the investigator. All AEs obtained by the investigator throughout the study were appropriately noted in the eCRF. SAEs were reported to the sponsor by e-mail or fax within 24 hours of their occurrence.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

DMF (Skilarence)

Reporting group description

The patients included in the clinical trial received Dimethyl fumarate (DMF) as stated in the datasheet, with gradual dose increments during the first 9 weeks.

Serious adverse events	DMF (Skilarence)
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 282 (1.77%)
number of deaths (all causes)	0
number of deaths resulting from adverse events	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
Additional description: Hospitalization of the patient. Not related to treatment.
subjects affected / exposed	1 / 282 (0.35%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Nervous system disorders
Cerebral infarction
Additional description: Posible relation to Skilarence. Permanent withdrawal of study treatment. Recovery with sequelae.
subjects affected / exposed	1 / 282 (0.35%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Blood and lymphatic system disorders
Eosinofilia
Additional description: Related to Skilarence. Permanent withdrawal of study treatment. Complete recovery.
subjects affected / exposed	1 / 282 (0.35%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Hepatobiliary disorders
Hepatitis acute
Additional description: Posible relation to Skilarence. Permanent withdrawal of study treatment. Complete recovery.
subjects affected / exposed	1 / 282 (0.35%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Infections and infestations
Appendicitis
Additional description: Not related to Skilarence. Temporary discontinuation of medication. Complete recovery.
subjects affected / exposed	1 / 282 (0.35%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	DMF (Skilarence)
Total subjects affected by non serious adverse events
subjects affected / exposed	272 / 282 (96.45%)
Vascular disorders
Hypertension
subjects affected / exposed	7 / 282 (2.48%)
occurrences all number	7
Surgical and medical procedures
Tooth extraction
subjects affected / exposed	5 / 282 (1.77%)
occurrences all number	6
General disorders and administration site conditions
Asthenia
subjects affected / exposed	7 / 282 (2.48%)
occurrences all number	8
Burning sensation
subjects affected / exposed	6 / 282 (2.13%)
occurrences all number	6
Fatigue
subjects affected / exposed	8 / 282 (2.84%)
occurrences all number	10
Feeling hot
subjects affected / exposed	9 / 282 (3.19%)
occurrences all number	10
Flushing
subjects affected / exposed	79 / 282 (28.01%)
occurrences all number	171
Hot flush
subjects affected / exposed	7 / 282 (2.48%)
occurrences all number	9
Inflammation
subjects affected / exposed	4 / 282 (1.42%)
occurrences all number	4
Malaise
subjects affected / exposed	8 / 282 (2.84%)
occurrences all number	9
Oedema peripheral
subjects affected / exposed	4 / 282 (1.42%)
occurrences all number	4
Pain
subjects affected / exposed	4 / 282 (1.42%)
occurrences all number	6
Pyrexia
subjects affected / exposed	5 / 282 (1.77%)
occurrences all number	5
Respiratory, thoracic and mediastinal disorders
Bronchitis
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3
Catarrh
subjects affected / exposed	22 / 282 (7.80%)
occurrences all number	23
Cough
subjects affected / exposed	4 / 282 (1.42%)
occurrences all number	5
Nasal congestion
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3
Oropharyngeal pain
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3
Pharyngitis
subjects affected / exposed	4 / 282 (1.42%)
occurrences all number	4
Rhinitis
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3
Investigations
Alanine aminotransferase increased
subjects affected / exposed	5 / 282 (1.77%)
occurrences all number	6
Weight decreased
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3
Nervous system disorders
Dizziness
subjects affected / exposed	14 / 282 (4.96%)
occurrences all number	15
Formication
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3
Headache
subjects affected / exposed	35 / 282 (12.41%)
occurrences all number	59
Insomnia
subjects affected / exposed	5 / 282 (1.77%)
occurrences all number	5
Paraesthesia
subjects affected / exposed	5 / 282 (1.77%)
occurrences all number	5
Syncope
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3
Blood and lymphatic system disorders
Eosinofilia
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3
Leukopenia
subjects affected / exposed	4 / 282 (1.42%)
occurrences all number	4
Lymphopenia
subjects affected / exposed	88 / 282 (31.21%)
occurrences all number	110
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	31 / 282 (10.99%)
occurrences all number	44
Abdominal distension
subjects affected / exposed	7 / 282 (2.48%)
occurrences all number	10
Abdominal pain
subjects affected / exposed	99 / 282 (35.11%)
occurrences all number	139
Abdominal pain upper
subjects affected / exposed	42 / 282 (14.89%)
occurrences all number	56
Constipation
subjects affected / exposed	10 / 282 (3.55%)
occurrences all number	13
Diarrhoea
subjects affected / exposed	141 / 282 (50.00%)
occurrences all number	253
Dyspepsia
subjects affected / exposed	12 / 282 (4.26%)
occurrences all number	12
Flatulence
subjects affected / exposed	10 / 282 (3.55%)
occurrences all number	13
Gastroenteritis
subjects affected / exposed	5 / 282 (1.77%)
occurrences all number	5
Gastrointestinal pain
subjects affected / exposed	8 / 282 (2.84%)
occurrences all number	10
Nausea
subjects affected / exposed	38 / 282 (13.48%)
occurrences all number	40
Toothache
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3
Vomiting
subjects affected / exposed	37 / 282 (13.12%)
occurrences all number	42
Skin and subcutaneous tissue disorders
Erythema
subjects affected / exposed	32 / 282 (11.35%)
occurrences all number	53
Pruritus
subjects affected / exposed	37 / 282 (13.12%)
occurrences all number	57
Psoriasis
subjects affected / exposed	4 / 282 (1.42%)
occurrences all number	4
Rash
subjects affected / exposed	4 / 282 (1.42%)
occurrences all number	4
Skin burning sensation
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3
Urticaria
subjects affected / exposed	4 / 282 (1.42%)
occurrences all number	4
Renal and urinary disorders
Haematuria
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	5 / 282 (1.77%)
occurrences all number	5
Back pain
subjects affected / exposed	13 / 282 (4.61%)
occurrences all number	16
Neck pain
subjects affected / exposed	6 / 282 (2.13%)
occurrences all number	8
Pain in extremity
subjects affected / exposed	6 / 282 (2.13%)
occurrences all number	8
Infections and infestations
Influenza
subjects affected / exposed	10 / 282 (3.55%)
occurrences all number	11
Nasopharyngitis
subjects affected / exposed	15 / 282 (5.32%)
occurrences all number	18
Pneumonia
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3
Respiratory tract infection
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3
Tooth abscess
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3
Upper respiratory tract infection
subjects affected / exposed	9 / 282 (3.19%)
occurrences all number	10
Urinary tract infection
subjects affected / exposed	6 / 282 (2.13%)
occurrences all number	6
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	5
Feeding intolerance
subjects affected / exposed	8 / 282 (2.84%)
occurrences all number	12
Hypertriglyceridaemia
subjects affected / exposed	3 / 282 (1.06%)
occurrences all number	3

More information

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

This is a single-arm study; comparative analyses could not be performed.

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Clinical trials

Clinical Trial Results: Open clinical study to assess long-term efficacy and safety of dimethyl fumarate in adults with moderate to severe chronic plaque psoriasis in real practice (DIMESKIN 1 Trial)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of subjects who achieved PASI75 response at Week 24 (ADO)

Primary: Number of subjects who achieved PASI75 response at Week 24 (ADO)

Primary: Number of subjects who achieved PASI75 response at Week 24 (LOCF)

Primary: Number of subjects who achieved PASI75 response at Week 24 (LOCF)

Primary: Number of subjects who achieved PASI75 response at Week 24 (MI)

Primary: Number of subjects who achieved PASI75 response at Week 24 (MI)

Secondary: Number of subjects who achieved PASI75 response over 52 weeks

Secondary: Number of subjects who achieved PASI75 response over 52 weeks

Secondary: Number of subjects who achieved PASI50 response over 52 weeks

Secondary: Number of subjects who achieved PASI50 response over 52 weeks

Secondary: Number of subjects who achieved PASI90 response over 52 weeks

Secondary: Number of subjects who achieved PASI90 response over 52 weeks

Secondary: Number of subjects who achieved PASI100 response over 52 weeks

Secondary: Number of subjects who achieved PASI100 response over 52 weeks

Secondary: Change in PASI score over 52 weeks

Secondary: Change in PASI score over 52 weeks

Secondary: Number of subjects who achieved a PGA 0 response over 52 weeks

Secondary: Number of subjects who achieved a PGA 0 response over 52 weeks

Secondary: Number of subjects who achieved a PGA 1 response over 52 weeks

Secondary: Number of subjects who achieved a PGA 1 response over 52 weeks

Secondary: Change in BSA score over 52 weeks

Secondary: Change in BSA score over 52 weeks

Secondary: Change in EVA score of pruritus over 52 weeks

Secondary: Change in EVA score of pruritus over 52 weeks

Secondary: Change in DLQI score over 52 weeks

Secondary: Change in DLQI score over 52 weeks

Secondary: Change in the satisfaction EVA score from Week 24 up to 52 or the discontinuation week

Secondary: Change in the satisfaction EVA score from Week 24 up to 52 or the discontinuation week

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Open clinical study to assess long-term efficacy and safety of dimethyl fumarate in adults with moderate to severe chronic plaque psoriasis in real practice (DIMESKIN 1 Trial)