Primary Objective:The primary objectives of the study are to demonstrate:• Superiority of LAS41008 versus placebo based on the proportion of subjects achievingPASI 75 at week 16 (a 75% reduction in the Psoriasis Area and Severity Index, PASI,…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary efficacy variables are:
- PASI 75 (= Response)
- Proportion of subjects achieving a score of "clear" or "almost clear" in the
Physician's Global Assessment (PGA)
Secondary outcome
- PASI 50, PASI 75, PASI 90, PASI 125
- Proportion of subjects achieving a score of "clear" or "almost clear" in the
Physician's Global Assessment (PGA)
- Body Surface Area (BSA)
- Treatment Success rate
- Remission rate
- Time to Relapse
- Time to Rebound (worsening of psoriasis over baseline value (PASI > 125%))
- Patient Benefit Index based on the Patient Need Questionnaire (PNQ) and the
Patient Benefit Questionnaire (PBQ)
Background summary
Psoriasis is a chronic inflammatory skin condition that is characterized by
hyperproliferation and abnormal differentiation of epidermal keratinocytes,
lymphocyte infiltration consisting mostly of T lymphocytes, and various
endothelial vascular changes in the dermal layer, such as
angiogenesis, dilation, and high endothelial venule formation. Meissner et al.
demonstrated that DMF causes a decrease in tube formation in human endothelial
cells in vitro. Although only formally authorized in Germany for the treatment
of psoriasis, FAEs are accepted by some dermatologists as effective systemic
therapies for both short-term and long-term treatment of moderate to severe
psoriasis also in other countries of the EU as well as the US, in accordance
with recent clinical therapy guidelines for psoriasis treatment.
Since its approval by the BfArM in 1994, Fumaderm® has become the most commonly
prescribed product for the systemic therapy of psoriasis in Germany
(approximately 66% of all prescriptions for systemic psoriasis therapy (EUROPSO
2002). In the S3 guideline, Fumaderm® is
recommended not only for induction therapy, but also for long-term therapy in
particular due to its good efficacy and safety profiles.
Fumaderm®, the reference product for this developmental program, is a
prescription only medicine containing DMF and the calcium, magnesium and zinc
salts of monoethylfumaric acid (MEF) as additional active ingredients. There is
evidence from clinical data indicating DMF as the main active ingredient of
Fumaderm® for the treatment of psoriasis.
Almirall S.A. intends to develop gastro-resistant tablet formulations of
dimethyl fumarate (DMF) for the treatment of moderate to severe chronic plaque
psoriasis in adult patients in need of systemic therapy. The tablets to be
developed will contain the active ingredient DMF in two strengths (30 mg and
120 mg) only, without the monoethylfumaric acid salts as contained in the
reference product Fumaderm®. Hence, these two tablet strengths correspond to
the respective dosages of DMF in the already authorized reference product,
Fumaderm®. In order to achieve an optimum
efficacy and tolerability profile, a low initial dose of 30 mg DMF is
recommended for the introduction of the therapy with 120 DMF. The development
rationale is based on proven efficacy and safety of Fumaderm® and the evidence
suggesting DMF is mainly responsible for the principal anti-psoriatic activity
of the product.
Study objective
Primary Objective:
The primary objectives of the study are to demonstrate:
• Superiority of LAS41008 versus placebo based on the proportion of subjects
achievingPASI 75 at week 16 (a 75% reduction in the Psoriasis Area and Severity
Index, PASI, compared to baseline.
• Superiority of LAS41008 versus placebo based on the proportion of subjects
achieving a score of *clear* or *almost clear* in the Physician*s Global
Assessment (PGA) after 16 weeks of treatment.
• Non-inferiority of LAS41008 compared to Fumaderm® regarding PASI 75 after 16
weeks of treatment.
Secondary Objectives:
a. Superiority of LAS41008 versus placebo based on changes on PASI, PGA after 3
and 8 weeks and BSA after 3, 8 and 16 weeks.
b. Non-inferiority of LAS41008 compared to Fumaderm® regarding PASI 75 after 3
and 8 weeks of treatment.
c. Assessment of the safety of LAS41008 compared to Fumaderm® and Placebo for
both treatment periods (30/120mg dimethyl fumarate).
d. - Assessment of the safety and efficacy of LAS41008 and Fumaderm® when
administered concomitantly with medicines known to have potential nephrotoxic
effects, e.g. angiotensin-converting enzyme, angiotensin II inhibitors and
statins.
Study design
This is a multicenter, randomized, three-arm, double-blind, adaptive, placebo
and comparator controlled phase III clinical study to investigate the efficacy
and safety of LAS41008 (30/120 mg) versus Fumaderm® (30/120 mg) and versus
placebo. It is planned to randomize approximately 690
patients with moderate to severe chronic plaque psoriasis at 50 centres in
Austria, Germany, Poland and the Netherlands (approximately 12 - 16 patients
per site). Each patient will be randomized to receive either LAS41008, the
comparator Fumaderm® or placebo in accordance with a randomization schedule of
2:2:1. The treatment scheme will be the same for each treatment group.
Intervention
Group 1:
LAS41008 containing 30 mg dimethyl fumarate per tablet, oral administration of
up to 3 x 1 tablet per day during week 1 - 3
LAS41008 containing 120 mg dimethyl fumarate per tablet, oral administration of
up to 3 x 2 tablets per day during week 4 - 16
Group 2:
Fumaderm® initial (LASW1835 initial) containing 30 mg dimethyl fumarate, oral
administration of up to 3 x 1 tablet per day
Fumaderm® (LASW1835) containing 120 mg dimethyl fumarate respectively, oral
administration of up to 3 x 2 tablets per day
Group 3:
Placebo
Duration of treatment:
Total duration of treatment period of 16 weeks.
Study burden and risks
Since Fumaderm® (which is marketed in Germany) contains the same active
substance as LAS41008 (in addition to other active substances), it is likely
that the side effects observed after intake of Fumaderm® may also occur in
patients taking LAS41008.
The following side effects have been observed in patients taking Fumaderm® and
are listed in the German Summary of Product Characteristics.
Rda. General Mitre 151
Barcelona 080022
ES
Rda. General Mitre 151
Barcelona 080022
ES
Listed location countries
Age
Inclusion criteria
- Signed and personally dated written informed consent
- Male / female
- Aged 18 years or older
- With a diagnosis of chronic plaque psoriasis for at least 12 months before enrollment in
the study
- With the severity of psoriasis defined as moderate to severe, as reflected in meeting all
the following criteria:
PASI > 10
BSA (body surface area) > 10 %
PGA moderate to severe
- With general good health, or a stable medical condition not considered likely to interfere
with the conduct of the clinical study, as determined by the investigator based upon
results of medical history, laboratory results and physical examination
- Prior therapy with systemic drugs for psoriasis that was discontinued
e.g. due to an adverse event or insufficient effect, or naïve to systemic
treatment but identified as a candidate for systemic treatment.- With a complete record of at least 12 months of other previous topical and systemic
treatments, if any.
- Adhering to the following wash-out periods :
2 weeks : Corticosteroids, Vitamin A analogues, Vitamin D analogues, Anthracene derivatives, Tar, Salicylic acid preparations
3 months : Biologics with antipsoriatic activity
1 month : Conventional systemic antipsoriatic drugs and phototherapy
6 months: Immunosuppressive medication (if not covered by any of the above treatments)
- For females of child-bearing potential: a negative serum pregnancy test at screening and
willing to use highly effective methods of birth control during the study period and for 60
days after the last dose of investigational product. Additionally they must agree to have
pregnancy tests while on study medication. 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 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 at least two years.
- Males (including those who have had vasectomy) must agree to use barrier
contraception while on study medication
- Willing to keep sun exposure reasonably constant and not to use tanning booths or other
UV light sources for the duration of the trial
Exclusion criteria
- For females: pregnant or lactating
- With a diagnosis of guttate, erythrodermic or pustular psoriasis
- With a hematological abnormality as follows: platelet count < 100,000/mm3, WBC count < 3,000 cells/ mm3, lymphocyte count < 1.000/µl, hemoglobin, hematocrit, or red blood cell count outside 30 % of the upper or lower limits of normal for the lab
- With a history of malignancies except for non melanoma skin cancer
- Suffering from significant gastrointestinal problems (ulcers, diarrhea, etc.)
- Known to have severe renal impairment
- Are detected to have abnormal liver enzymes
(a) if an enzyme is >3x the upper limit of the normal range (AST (SGOT) ALT (SGPT),
gamma-GT, alkaline phosphatase (ALP))
(b) if bilirubin is >2xULN, for the other liver enzymes >2xULN
- With active infectious disease
- On systemic therapy with drugs that may interfere with the investigational products taken within the defined wash-out period
- With a history of alcohol or drug abuse
- Known HIV-positive status or suffering from any other immunosuppressive disease
- Known to be hypersensitive to ingredients of the investigational products
- Previous enrolled in this study or participating in any other drug investigational trial within the 30 days (or five half-lives whichever is longer) prior to enrolment.
- Not willing to give consent for transmission of personal "pseudonymised" data
- Unable to comply with the requirements of the study or who in the opinion of the investigator should not participate in the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-000055-13-NL |
| CCMO | NL41945.091.12 |