E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Chronic Hand Dermatitis (CHaD) Refractory to Topical Therapy |
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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 |
To assess the safety of alitretinoin |
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E.2.2 | Secondary objectives of the trial |
To determine the efficacy of the alitretinoin in patients with severe refractory CHaD, based on: - proportion of patients with response (Physician's Global Assessment rating of clear or almost clear; - proportion of patients with at least partial response (Physician's Global Assessment rating of clear, almost clear or mild); - modified Total Lesion Symptom Score (mTLSS), - Patient's Global Assessment (PaGA), - Patient Defined Outcome (PaDO), - extent of disease, - intensity of pain and pruritus, |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Male patients, or female patients if post-menopausal, or hysterectomized, or if pre-menopausal and willing to use two methods of contraception under supervision of the investigator or a gynecologist. - Aged 18 to 75 years - Chronic hand dermatitis; all types of chronic hand dermatitis including hyperkeratotic, vesicular (e.g. pompholyx), and fingertip dermatitis, and fulfilling the following criteria: ~lasting for at least 6 months since initial diagnosis ~rated severe, according to the Physician Global Assessment (PGA) ~refractory to standard non-medicated therapy, including skin moisturization and protection, and avoidance of relevant irritants and allergens ~refractory to topical corticosteroid therapy, with unsatisfactory outcome (no response, transient response to ongoing therapy, or lack of tolerability) after at least 8 weeks of treatment within previous 12 months, unless contraindicated or not tolerated - Written informed consent provided |
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E.4 | Principal exclusion criteria |
- Patients unable to comply with the requirements of the study - Female patients who are pregnant or who plan to become pregnant or who are breast feeding - Female patients of childbearing potential who cannot use or will not commit to using two effective forms of contraception simultaneously under supervision of the investigator or a gynecologist - Patients whose disease is adequately controlled by standard non-medicated therapy (skin moisturization and protection, avoidance of irritants and allergens) and standard topical corticosteroid therapy - Patients with known hypersensitivity to other retinoids or vitamin A derivatives, or to any study medication component, especially soybean oil and partly hydrogenated soybean oil - Patients treated with systemic therapy e.g. corticosteroids, retinoids, immunosuppressants, within four weeks before start of trial treatment (use of inhaled steroids is permitted) - Patients treated with phototherapy UVB, PUVA, Grenz rays, or X-rays within four weeks before start of trial treatment - Patients with known clinically relevant allergic contact dermatitis of the hands, as demonstrated by a prior positive patch test, who have not made a reasonable effort to avoid relevant contact allergens - patients presenting with a) psoriasis lesions (including palmo-plantar psoriasis, b) atopic dermatitis lesions requiring medicated treatment, c) acute (non-chronic) episodes of pompholyx/ dyshydrosis or of contact dermatitis d) active bacterial, fungal or viral infections of the hands - Patients presenting with any other skin disease likely to interfere with the conduct of the study and/or the evaluation of the results - Patients with any serious medical condition which, in the opinion of the investigator, may interfere with the safety or the evaluation of the study, including chronic heart failure, recent myocardial infarction (chest pain within the last 3 months with changes in ECG and/or increased cardiac enzymes), chronic renal failure, chronic liver failure, unstable hypothyroidism, chronic biliary disease, uncontrolled diabetes mellitus - Patients known to be immunocompromised - Patients with ALT and/or AST >2.5x ULN - Patients with fasting triglyceridemia > 1,5x ULN - Patients with cholesterol >1,5 x ULN and/or LDL/cholesterol > 1,5 x ULN - Patients with hemoglobin <0,9 LLN - Patients receiving drugs with a potential for drug-drug interaction such as systemic tetracyclines, ketoconazole, erythromycin or clarithromycin, simvastatin, or St. John’s wort within one week, or receiving systemic itraconazole within 2 weeks, before start of trial treatment. - Patients receiving topical retinoids, macrolides, tacrolimus, or pimecrolimus on affected areas, or taking vitamin supplements containing > 2000 IU vitamin A within one week before start of trial treatment - Patients included in the study of an investigational drug within 2 months before start of trial treatment - Patients with an active major psychiatric disorder (e.g. Major Depressive Disorder, Generalized Anxiety Disorder, Bipolar Disorder (I or II), or schizophrenia) |
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the safety of alitretinoin by means of descriptive analysis of Adverse Events, laboratory data, CES-D and GHQ questionnaires and x-ray/DXA. |
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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 | Yes |
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 | Information not present in EudraCT |
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
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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 | 1 |
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 | 1 |