moderate to severe chronic plaque psoriasis MedDRA version: 17.1 Level: LLT Classification code 10071117 Term: Plaque psoriasis System Organ Class: 100000004858 MedDRA version: 17.1 Level: LLT Classification code 10050576 Term: Psoriasis vulgaris System Organ Class: 100000004858
Conditions
Interventions
Product Code: LAS41008 30 mg
Pharmaceutical Form: Gastro-resistant tablet
INN or Proposed INN: Dimethyl (E)-butenedioate
CAS Number: 624-49-7
Other descriptive name: DIMETHYL FUMARATE
Concentration un
Sponsors
Almirall S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
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 wash-out periods as stated in the protocol - 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 (except vasectomized males) 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 590 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
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 - 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 - Previous failed therapy with fumaric acid esters either due to inadequate efficacy or lack of tolerability.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of the study are: - Superiority of LAS41008 versus placebo based on the proportion of subjects achieving PASI 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 LASW1835 (internal code for Fumaderm®) regarding PASI 75 after 16 weeks of treatment. ;Secondary Objective: Secondary Objectives: - Superiority of LAS41008 versus placebo based on changes on PASI, PGA after 3 and 8 weeks and BSA after 3, 8 and 16 weeks. - Non-inferiority of LAS41008 compared to Fumaderm® regarding PASI 75 after 3 and 8 weeks of treatment. - Assessment of the safety of LAS41008 compared to Fumaderm® and placebo for both treatment periods (30/120mg dimethyl fumarate). - 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.;Primary end point(s): 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);Timepoint(s) of evaluation of this end point: week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy variables are: - 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) ;Timepoint(s) of evaluation of this end point: at week 3 and 8: - PASI 75 - Proportion of subjects achieving a score of “clear” or ”almost clear” in the Physician’s Global Assessment (PGA) at week 3, 8 and 16: - Body Surface Area (BSA) - PASI 50, PASI 90, PASI 125 - Treatment Success rate - Remission rate At baseline: - Patient Benefit Index based on the Patient Need Questionnaire (PNQ) At end of treatment and after 2 months Patient Benefit Questionnaire (PBQ) At any time: - Time to Relapse - Time to Rebound (worsening of psoriasis over baseline value (PASI > 125%)) | — |
Countries
Austria, Germany, Netherlands, Poland
Contacts
Public ContactDr. Wolf-Godehard Ocker
Almirall S.A.
Outcome results
None listed