LAS41008 in Moderate to Severe Chronic Plaque Psoriasis

Study Overview
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Brief Summary
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The aim of the study is to evaluate the efficacy and safety of LAS41008 in comparison to active control and placebo in patients with moderate to severe chronic plaque psoriasis

Official Title
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A Multi-center, Randomized, Double-blind, Three-arm, 16 Week, Adaptive Phase III Clinical Study to Investigate the Efficacy and Safety of LAS41008 vs LASW1835 and vs Placebo in Patients With Moderate to Severe Chronic Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: LAS41008
* Drug: LASW1835
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 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 Topical treatment Wash-out Period Corticosteroids Vitamin A analogues Vitamin D analogues Anthracene derivatives Tar Salicylic acid preparations 2 weeks Systemic treatment Biologics with antipsoriatic activity 3 months Conventional systemic antipsoriatic drugs and phototherapy 1 month Immunosuppressive medication (if not covered by any of the above treatments) Cytostatics 6 months Medications with known harmful influences on the kidneys 5 x halftime 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 significant renal impairment Are detected to have abnormal liver enzymes >2x the upper limit of the normal range 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LAS41008<br>up to 6 tablets/ day for 16 weeks double blind treatment period, randomized gastric resistant tablet | Drug: LAS41008<br>* gastric resistant tablet, weekly up-titration up to maximal tolerated dosage<br>* Other names: Verum;|
| Placebo Comparator: Placebo<br>up to 6 tablets/ day for 16 weeks randomized, double blind gastric resistant tablet | Drug: Placebo<br>* gastric resistant tablet, weekly up-titration up to maximal tolerated dosage<br>|
| Active Comparator: LASW1835<br>double blind, randomized gastric resistant tablet up to 6 tablets/ day for 16 weeks | Drug: LASW1835<br>* gastric resistant tablet, weekly up-titration up to maximal tolerated dosage<br>* Other names: Fumaderm initial/ Fumaderm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PASI 75 | Reduction of PASI by 75% from baseline to week 16 | 16 weeks | 
| Physician Global Assessment, PGA | Change in PGA from baseline to week 16 | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Surface Area, BSA | Change in BSA from baseline to week 3, 8, 16 and follow up | 16 weeks | 
| Dermatological Life Quality Index, DLQI | Change in DLQI from baseline to week 3, 8, 16 and follow up | 16 weeks | 
| PASI 75 | Change in PASI 75 from baseline to week 3 and 8 and follow up | week 3 and 8 | 
| PGA | Change in PGA from baseline to week 3 and 8 and follow up | week 3 and 8 | 
| Adverse events | Ongoing safety profile over the course of the study (treatment phase and follow up) | ongoing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psoriasis, systemic treatment