| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Fumaderm initial / Fumaderm will be used in this CT completely "in-label", i.e. for the treatment of adult patients of both genders with moderate to severe plaque psoriasis in so far as a solely topical treatment is not sufficient. The treatment will last for a defined study period of 16 weeks (and facultatively over an additional 4 weeks during the follow-up). |
|
| MedDRA Classification |
| 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 |
Analysis of the toproteome of skin tissue and of peripheral blood mononuclear cells under standard treatment of moderate to severe psoriasis with Fumaderm initial / Fumaderm in an envisioned optimum of 10 patients. To that goal a total of 15 patients will be recruited to enter the study medication, given a generally known portion of about 25% of patients not tolerating the drug.
For the fore-mentioned scientific purpose the following specimen collections will be performed for the subsequent analysis by multi epitope ligand cartography (=MELC):
1) Skin punch biopsies of 6 mm in diameter will be taken in local anesthesia before the beginning of the treatment (from involved and uninvolved psoriatic skin) and at weeks 8 and 16 after the beginning of the treatment (from originally involved skin, representative areas).
2) Peripheral venous blood specimes of 10 ml each will be drawn from the forearm or cubital vein before the beginning of the treatment and at 8 and 16 weeks later.
|
|
| E.2.2 | Secondary objectives of the trial |
- Determination of anti-psoriatic treatment efficacy of Fumaderm initial / Fumaderm as well as detection of responders and non-responders by determination of the following established standard parameters in the course of the above mentioned treatment: 1) psoriasis area and severity index (PASI), 2) physician`s global assessment (PGA), 3) pruritus score, and 4) dermatology life quality index (DLQI).
- Determination of treatment tolerability and safety by the detection of possibly occuring adverse events. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
According to approved label status of Fumaderm initial / Fumaderm:
Adult patients with moderate to severe plaque psoriasis in so far as solely topical treatment is not sufficient.
- No pre-treatment with Fumaderm initial / Fumaderm in the patient´s history.
- The patient is able to understand the study, capable to give informed consent and available for the 20 weeks of the trial.
- Written informed consent.
- Age of more than 18 years.
- Psoriasis area and severity index (PASI) of more than 10 or
involvement of body surface by psoriasis for more than 10% or
dermatology life quality index (DLQI, according to Finlay & Kahn) of more than 10.
- Consideration of the following wash-out-intervals before the start of study medication:
i) 2 weeks for antipsoriatic topical drugs (vitamin D and analogues, dithranol, corticosteroids, tar, tazarotene),
ii) 4 weeks for conventional antipsoriatic systemic drugs (cyclosporine, methotrexate, acitretin),
iii) 4 weeks for uv-treatment inclusive balneo-photo-therapy,
iv) 3 months for infliximab, adalimumab, golimumab, etanercept, and efalizumab,
v) 6 months for ustekinumab, and
vi) 6 months for any investigational compound / drug or any investigational treatment.
- Willingness of the study participant, that during the study treatment none of the under i) to vi) aforementioned treatments will be applied.
- In case of treatment with a beta-blocker, ACE-inhibitor, anti-malaria drug (resochin), interferon or lithium: stable medication with these agents for at least 4 weeks before the start of the study medication.
- No foreseeable necessity for vaccination with a live-vaccine during 4 weeks before the start of the study medication, during 16 weeks of study medication and during 12 weeks afterwards.
- Willingness to keep natural sun light exposure adequately constant and to avoid the use of artificial uv exposure (solarium).
- Use of anticonception in female study participants of child bearing potential under study medication. Recommendation of a highly effective method of birth control (i.e. with a failure rate of less than 1% per year).
|
|
| E.4 | Principal exclusion criteria |
According to approved label status of Fumaderm initial / Fumaderm.
- Known hypersensitivity towards the active compounds, i.e. dimethylfumarate, ethylhydrogenfumarate calcium-, magnesium- or zinc-salt, or to any other constituent of Fumaderm® initial / Fumaderm®.
- Severe gastrointestinal diseases, alike Ulcus ventriculi and Ulcus duodeni.
- Severe liver and kidney diseases.
- Hematologic diseases.
- Medium-severe to severe heart insufficiency (NYHA III/IV).
- Indication for a demyelinating disease (e.g. multiple sclerosis) in the patient`s history or in the history of a family member.
- Minimal psoriasis, alike localized plaque psoriasis or chronic stationary plaque psoriasis with an extent of less than 10% of body surface.
- Psoriasis of the pustular subtype.
- Persons under the age of 18 years.
- Pregnancy.
- Breast feeding.
- Relevant pathologic laboratory findings for blood cell count, liver- and kidney- parameters as well as urine status.
- On-going systemic treatment with methotrexate, retinoid, psoralen, cyclosporine, immunosuppressive drugs/agents, cytostatics and drugs with known nephrotoxicity.
- On-going topical treatment with fumaric acid derivatives, e.g. as ointments and/or bath preparations.
- HIV-infection.
- Hepatitis B oder C in the patient`s history.
- Malignancy of recent relevance.
- Serious other reason out of the investigator`s judgement.
Criteria for premature discontuinuation are:
According to label in case of:
- Substantial decrease of blood leukocyte count (especially with counts below 3000/µl) or other blood cell alterations.
- Increase of creatinin.
- Relevant disturbances of kidney and liver function.
According to an expert consensus conference [P. Altmeyer, E. Christophers et al.: "Leitlinien zur Therapie mit Fumarsäureestern"] dose reduction or complete stop of treatment is necessary under the following circumstances:
i) increase of serum creatinin for more than 30% of the level before treatment,
ii) proteinuria,
iii) decrease of leucocytes below 3.000/µl,
iv) decrease of lymphocytes below 500/µl and
v) persistant eosinophilia of more than 25 %.
Other absolute indications for an early termination of study medication are:
- Subjective and/or objective non-tolerable gastrointestinal reactions and flush-reactions.
- Substantial clinical worsening of psoriasis, defined as a PASI-increase by 50% as compared to the level before study treatment.
- Grade 3 system toxicity.
- Grade 4 adverse event (AE) or serious adverse event (SAE) due to study medication.
- Severe Infection (grade 3) including sepsis.
- Occurence of pregnancy.
- Need for vaccination with a live-vaccine.
- Withdrawal of consent.
The treatment may be discontinued under the following conditions:
- Lack of subject compliance.
- Significant protocol deviation.
- Upon decision of the investigator due to other serious reasons. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
- The primary endpoint of the clinical trial is the antipsoriatic treatment of the study participants with a standard "in-label" Fumaderm initial / Fumaderm treatment for 16 weeks. At that time point the individual PASI-response and the PASI-50-response- as well as PASI-75-response-rates will be recorded. Additionally the responder-/non-responder-ratio will be determined, as well as the drop-out-rate primarily due to possible drug intolerance.
- The primary study parameter is the analysis of the topoproteome in skin tissue and peripheral blood mononuclear cells as detected by multi epitope ligand cartography (= MELC). |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Information not present in EudraCT |
| E.6.5 | Efficacy | Information not present in EudraCT |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Proteomic and Topoproteomic |
|
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| 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 | Information not present in EudraCT |
| 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 | 9 |
| E.8.9.1 | In the Member State concerned days | |
Print
