| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| moderate to severe chronic plaque psoriasis |
| mittelschwere bis schwere Formen der Psoriasis vulgaris |
|
| E.1.1.1 | Medical condition in easily understood language |
| moderate to severe chronic plaque psoriasis |
| mittelschwere bis schwere Formen der Psoriasis vulgaris |
|
| 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 | 17.1 |
| 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.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10050576 |
| E.1.2 | Term | Psoriasis vulgaris |
| E.1.2 | System Organ Class | 100000004858 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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.
|
|
| E.2.2 | Secondary objectives of the trial |
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. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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
|
|
| E.4 | Principal 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. |
|
| E.5 End points |
| E.5.1 | 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) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | 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)
|
|
| E.5.2.1 | 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%))
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| 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 | 40 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 65 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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