Clinical Trials Register

Summary
EudraCT Number:	2018-004010-18
Sponsor's Protocol Code Number:	M-41008-47
National Competent Authority:	Ireland - HPRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-04-03
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Ireland - HPRA

A.2

EudraCT number

2018-004010-18

A.3

Full title of the trial

An Open Label, Multi-Center, 24 Week, Exploratory Study to Assess the Efficacy and Safety of Skilarence® (Dimethyl Fumarate) in Patients with Moderate Plaque Psoriasis

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

The use of Skilarance® to treat patients with moderate plaque psoriasis

A.3.2

Name or abbreviated title of the trial where available

SMR-3612

A.4.1

Sponsor's protocol code number

M-41008-47

A.5.4

Other Identifiers

Name:

CRO

Number:

SMR-3612

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Almirall Ltd
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Almirall Ltd
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Smerud Medical Research UK Limited
B.5.2	Functional name of contact point	Dr Amanda Knock
B.5.3	Address:
B.5.3.1	Street Address	Suite 1S-B Trafford House, Chester Road
B.5.3.2	Town/ city	Manchester
B.5.3.3	Post code	M32 0RS
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44 (0)1618708129
B.5.6	E-mail	regulatory.uk@smerud.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Skilarence (30mg)
D.2.1.1.2	Name of the Marketing Authorisation holder	Almirall, S.A
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Skilarence (30mg)
D.3.4	Pharmaceutical form	Gastro-resistant tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DIMETHYL FUMARATE
D.3.9.1	CAS number	624-49-7
D.3.9.3	Other descriptive name	DIMETHYL FUMARATE
D.3.9.4	EV Substance Code	SUB13608MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Skilarence (120mg)
D.2.1.1.2	Name of the Marketing Authorisation holder	Almirall, S. A
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Skilarence (120mg)
D.3.4	Pharmaceutical form	Gastro-resistant tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DIMETHYL FUMARATE
D.3.9.1	CAS number	624-49-7
D.3.9.3	Other descriptive name	DIMETHYL FUMARATE
D.3.9.4	EV Substance Code	SUB13608MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	120
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderate Plaque Psoriasis

E.1.1.1

Medical condition in easily understood language

psoriasis

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10071117
E.1.2	Term	Plaque psoriasis
E.1.2	System Organ Class	100000004858

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The main objective of this study is to assess the efficacy of Skilarence® (Dimethyl Fumarate) at week 24 of treatment as measured by static Physician’s Global Assessment score (sPGA) multiplied by percentage Body Surface Area (BSA).

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are to assess impact on:

o Dermatology Life Quality Index (DLQI)
o Psoriasis Area and Severity Index (PASI)
o Static Physician´s Global Assessment (sPGA)
o Body Surface Area (BSA)
o Patient satisfaction with Skilarence® treatment efficacy on psoriasis
in patients treated with Skilarence® (Dimethyl Fumarate) for 24 weeks, compared to baseline
• To describe the safety profile in moderate patients treated with Skilarence® (Dimethyl Fumarate) over 24 weeks

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A research sub-study is appended to the final version of the main study protocol.

The aim of this research sub-study is to determine the molecular and cellular phenotype of moderate psoriasis patients in response to treatment with Skilarence®.

E.3

Principal inclusion criteria

In order to participate in this study patients must meet all of the following inclusion criteria:
• Signed and dated informed consent
• Males and females ≥ 18 years
• Diagnosis of plaque psoriasis at least 6 months prior to screening visit
• BSA ≥ 5% at screening and baseline
• PASI score between 5 and 10 at screening and baseline
• Static Physician´s Global Assessment (sPGA) of 3 (moderate) based on a 6 point scale at screening and baseline
• DLQI ≥ 5 at screening and baseline
• Wash-out period for topical treatments (≥ 2 weeks) and for phototherapy and other non-biologic systemic therapies (≥4weeks) prior to baseline (Visit 2).
• A candidate to receive systemic treatment for psoriasis based on physician clinical judgement
• Women of child-bearing potential must have a negative serum pregnancy test at Visit 1 (Screening) and a negative urine pregnancy test at Visit 2 (Baseline)
• Females of child-bearing potential must be willing to use highly effective methods of birth control during the study period. Additionally they must agree to have pregnancy tests while on Skilarence®. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some Intrauterine Devices (IUDs), sexual abstinence or vasectomized partner. Female patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for 12 months or more.
• No previous use of biologic treatments for psoriasis or psoriatic arthropathy

E.4

Principal exclusion criteria

In order to participate in the study patients must not meet any of the following exclusion criteria:
• Females who are pregnant, breast feeding, refuse to use birth control methods or who wish to become pregnant during the study period
• Diagnosis of other psoriasis clinical subtypes such as guttate, erythrodermic or pustular psoriasis
• Diagnosis of active psoriatic arthropathy
• Diagnosis of Fanconi syndrome
• Baseline white blood cell count <3.0x109/L or lymphocyte count <1.0x109/L
• Previous malignancies (except for non-melanoma skin cancer)
• Severe impaired renal function: Severe renal impairment (creatinine clearance < 30 mL/min, estimated GFR using Modification of Diet in Renal Disease (MDRD) formula)
• Severe hepatic impairment (Child Pugh class C)
• Abnormal liver enzymes defined by:
• AST (SGOT), ALT (SGPT) and alkaline phosphatase (ALP) >3x the upper limit of the normal range (ULN) should be excluded. If bilirubin is >2x ULN, then an AST, ALT or ALP of >2x ULN is exclusionary. Elevated gamma-GT (GGT) values exceeding >3x ULN are allowed but these GGT cases will be carefully assessed alongside other clinical and laboratory data by the investigator
• History of severe gastrointestinal problems
• History of active infectious disease
• Known human immunodeficiency virus (HIV)-positive status or suffering from any other immunosuppressive disease
• Known to be hypersensitive to any of the ingredients of Skilarence®.
• Previously enrolled in any study or participating in any other drug investigational trial within the 30 days (or five half-lives of the investigational product studied, whichever is longer) prior to enrolment.
• History of major psychiatric illness
• Unable to comply with the requirements of the study or who in the opinion of the investigator should not participate in the study

E.5 End points

E.5.1

Primary end point(s)

The primary outcome measure for this study is defined as;
The mean percentage change from baseline in the product of sPGA and BSA (%) (sPGA*BSA) at week 24 of treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24 of treatment with Skilarence

E.5.2

Secondary end point(s)

• Percentage of patients with PASI 75 (≥75% reduction from baseline) at weeks 12, 16 and 24
• Percentage of patients with PASI 50 (≥50% reduction from baseline) at weeks 12, 16 and 24
• Percentage change from baseline in PASI score at weeks 12, 16 and 24
• Percentage of patients that achieve PASI score of <1, <3 and <5 at week 24
• Absolute PASI scores at weeks 12, 16 and 24
• Percentage change from baseline in BSA at weeks 12, 16 and 24
• Percentage change from baseline in DLQI at weeks 12, 16 and 24
• Percentage change from baseline in sPGA*BSA at weeks 12 and 16
• Percentage of patients achieving a score of “clear” or ”almost clear” in sPGA at weeks 12, 16 and 24.

Safety Variables:
• Physical examination
• Vital signs
• Serum chemistry, haematology, urinalysis
• Adverse events

E.5.2.1

Timepoint(s) of evaluation of this end point

Weeks, 12, 16 and 24

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

140

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

150

F.4.2.2

In the whole clinical trial

150

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

At the end of the study, patients could be given the opportunity to continue taking Skilarence for up to two years following discussion with their study doctor. Skilarence may be provided free of charge, where it is not reimbursed by the local prescribing health care system. Almirall Ltd. as the sponsor will carry the liability for the provision of Skilarence outside of the study.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-05-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-06-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-06-24

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