| 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 | |
| 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 demonstrate that the response rate based on Physician Global Assessment (PGA) in one or both active treatment groups is superior to the response rate in the Placebo group at the end of therapy (Week 12 or 24), or at the latest assessment for patients who withdraw prematurely | |
| E.2.2 | Secondary objectives of the trial | - To demonstrate the efficacy of the tested dose regimens of BAL4079 in patients with severe refractory CHaD, based on secondary efficacy parameters Modified Total Lesion Symptom Score (mTLSS), Patient’s Global Assessment (PaGA), and extent of disease
- To compare time to response between active treatment groups
- To determine time to relapse of CHaD for active treatment and placebo groups
- To assess the safety of tested dose regimens of BAL4079 in patients with severe refractory ChaD | |
| 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 premenopausal 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 topical 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 on-going therapy, or lack of tolerability) after at least 8 weeks of treatment within the previous 6 months, including Class 1 topical steroids (most potent; for example, 0.05% clobetasol dipropionate ointment) applied for at least 4 weeks or as indicated in label, unless contradicted or not tolerated
- Written informed consent provided | |
| 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, but whose disease has relapsed following discontinuation of these treatments
- 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, and unable to avoid exposure to the allergen or patients presenting with a) psoriasis lesions (including suspicion of palmo-plantar psoriasis), b) atopic dermatitis lesions requiring medicated treatment, c) acute (non-chronic) episodes of contact dermatitis or of pompholyx/dyshydrosis 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 infection, chronic renal failure, chronic liver failure, thyroid disorders, chronic biliary disease, uncontrolled diabetes mellitus
- Patients known to be immunocompromised
- Patients with ALT and/or AST >2.5x ULN
- Patients with fasting triglyceridemia > 2x ULN
- Patients with cholesterol >2x ULN and/or LDL/cholesterol > 2x ULN
- Patients with hemoglobin < 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 a score of 20 or more on the CES-D depression scale at screening, or with a history of major psychiatric disorder (e.g. Major Depressive Disorder, Generalized Anxiety Disorder, Bipolar (I or II), or schizophrenia) | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | Physician’s Global Assessment (PGA) of efficacy | |
| 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 | Yes |
| 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 | 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 | Yes |
| 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 | Yes |
| 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 | |
| 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 | | Last visit of last subject | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
