Clinical Trials Register

Summary
EudraCT Number:	2013-003757-22
Sponsor's Protocol Code Number:	H553000-1309
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-01-22
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

Germany - BfArM

A.2

EudraCT number

2013-003757-22

A.3

Full title of the trial

A phase IIa, 28-day treatment, multi-center, randomized, comparator-controlled, observer-blind trial with intra-individual left/right comparison to investigate the anti-psoriatic efficacy and the safety of an LAS41004 formulation in comparison to an active reference in patients with mild to moderate plaque psoriasis

A.3.1

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

A.4.1

Sponsor's protocol code number

H553000-1309

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 Hermal GmbH
B.1.3.4	Country	Germany
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 Hermal GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	bioskin GmbH
B.5.2	Functional name of contact point	Wiebke Havemeister, PhD
B.5.3	Address:
B.5.3.1	Street Address	Burchardstrasse 17
B.5.3.2	Town/ city	Hamburg
B.5.3.3	Post code	20095
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4904060689735
B.5.5	Fax number	+4904060689730
B.5.6	E-mail	wiebke.havemeister@bioskincro.de

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	No
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	LAS 41004
D.3.2	Product code	LAS 41004
D.3.4	Pharmaceutical form	Gel
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Topical use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BEXAROTENE
D.3.9.1	CAS number	153559-49-0
D.3.9.4	EV Substance Code	SUB00795MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.0
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	BETAMETHASONE DIPROPIONATE
D.3.9.4	EV Substance Code	SUB00783MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.064
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	Comparator
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	Daivobet® ointment
D.2.1.1.2	Name of the Marketing Authorisation holder	LEO Pharma A/S
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Daivobet® ointment
D.3.4	Pharmaceutical form	Ointment
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Topical use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CALCIPOTRIOL
D.3.9.1	CAS number	112828-00-9
D.3.9.4	EV Substance Code	SUB06046MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.05
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	BETAMETHASONE DIPROPIONATE
D.3.9.4	EV Substance Code	SUB00783MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.0643
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

patients with moderate stable chronic plaque-type 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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the anti-psoriatic efficacy and safety of the combination of BX plus BDP in a topical formulation and by reference to Daivobet® ointment (calcipotriol plus BDP).

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•men or women aged 18 years or older;
•mild to moderate stable chronic plaque-type psoriasis with at least two symmetrical lesions with a treatment area of 20 – 300 cm² and a TSS of ≥ 6;
•the physical examination paying particular attention to the application area must be without further disease findings (other than psoriasis) unless the investigator considers an abnormality to be irrelevant to the outcome of the trial;
•female volunteers of childbearing potential* must agree to use for one month prior to start of IMP application, during the trial and for at least one month after EoT reliable methods of contraception with a failure rate of less than 1 % per year (e.g. contraceptive implants of injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner). During the trial an additional barrier method (e.g. condoms) must be used. In the case of men with partners of childbearing potential* willingness of using condoms during the study conduct and for 1 month after end of treatment.
•written informed consent obtained.
* Females NOT of childbearing potential are defined as those who have been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (defined as continuous amenorrhea of at least two years)

E.4

Principal exclusion criteria

•severe forms of psoriasis or forms of psoriasis other than chronic plaque psoriasis, including:
-erythrodermic, exfoliative or pustular psoriasis;
-psoriatic arthritis;
-unstable psoriasis, with a change in severity within the last 6 weeks prior screening;
•treatment with any locally acting medications (including anti-psoriatics like vitamin D analogues, dithranol) which might counter or influence the trial aim within 2 weeks preceding the treatment phase of the trial and during the trial;
•treatment with any systemic medications which might counter or influence the trial aim (including anti-psoriatics like corticosteroids, cytostatics or medications which are known to provoke or aggravate psoriasis (e.g. ß-blocker, anti-malarial drugs, lithium) or phototherapy/PUVA within 4 weeks preceding the treatment phase of the trial and during the trial;
•treatment with vitamin A supplements;
•treatment with any biologics within 3 months preceding the treatment phase of the trial and during the trial, or in the case of ustekinumab, within 6 months;
•treatment with any immunosuppressive medication within 6 months preceding the treatment phase of the trial and during the trial;
•known allergic reactions, irritations or hypersensitivity to the active ingredients (BX, BDP or calcipotriol) or any other ingredient of the IMPs;
•contraindications according to summary of product characteristics (SmPC) of the active comparator:
-hypersensitivity against the substance or to any of the excipients;
-erythrodermic, exfoliative and pustular psoriasis
-virus-induced skin lesions (e.g. herpes, varicella)
-known calcium metabolism disorders;
-viral (e.g. herpes or varicella) lesions of the skin, fungal or bacterial skin infections, parasitic infections;
-skin manifestations in relation to tuberculosis or syphilis;
-perioral dermatitis;
-atrophic skin, striae atrophicae;
-fragility of skin veins;
-ichthyosis;
-acne vulgaris;
-rosacea;
-ulcers;
-wounds;
-perianal and genital pruritus.
•concomitant use of ketoconazole, itraconazole, erythromycin, grapefruit juice or gemfibrozil or application of products that contain DEET (N,N-diethyl-m-toluamide);
•evidence of drug or alcohol abuse;
•pregnancy or nursing;
•symptoms of a clinically significant illness that may influence the outcome of the trial in the 4 weeks before first treatment and during the trial;
•vaccination within the 6 days prior to the trial;
•history of malignancy of any organ system (less than 5 years ago);
•participation in the treatment phase of another clinical trial within the last 4 weeks prior to the first administration of IMPs in this clinical trial or during the trial;
•in the opinion of the investigator or physician performing the initial examination the patient should not participate in the trial, e.g. due to probable noncompliance or inability to understand the trial and give adequately informed consent;
•close affiliation with the investigator (e.g. a close relative) or persons working at bioskin GmbH, the other sites or for the sponsor;
•patient is institutionalized because of legal or regulatory order.

E.5 End points

E.5.1

Primary end point(s)

The primary variable is the total sign score (TSS) defined as the sum of individual scores for erythema, scaling and infiltration using a 5-point scale (0 = absent, 1 = slight, 2 = moderate,
3 = severe, 4 = severest possible) for each sign clinically assessed (visually and, where relevant, by palpating the test area).
The primary endpoint is the change from baseline in the TSS of each treated plaque on Day 29 (EoT).

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 29

E.5.2

Secondary end point(s)

•Changes from baseline in the TSS on Days 4, 8, 15, and 22 will be evaluated for each treated plaque in a similar way to the primary analysis to assess the onset of treatment effect
•Summary statistics will be given for the primary variable TSS and its changes from baseline by treatment and visit for each site.
All the following secondary endpoints will be summarized descriptively by treatment:
•Changes from baseline in the score for each of the individual signs (erythema, scaling and infiltration) of each treated plaque on Days 4, 8, 15, 22 and 29
•Physician’s global assessment (PGA) score of each treated plaque on Days 1, 4, 8, 15, 22 and 29

E.5.2.1

Timepoint(s) of evaluation of this end point

Days 4, 8, 15, 22 and 29
PGA Days 1, 4, 8, 15, 22, 29

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

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

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

Yes

E.8.1.7.1

Other trial design description

observerblind

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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 months

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:

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.4.2.2

In the whole clinical trial

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)

No further treatment is intended.

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

2014-05-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-03-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-10-13

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