E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Pustular form of Psoriasis |
|
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050185 |
E.1.2 | Term | Palmoplantar pustulosis |
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 |
Determine the response, based on the palmo-plantar pustulosis psoriasis area and severity index (PPPASI) at the end of treatment (week 24). |
|
E.2.2 | Secondary objectives of the trial |
- assess the response of pustular lesions to total pustular count
- assess the response to psoriasis lesions in locations other than the hands to treatment
- assess the response of nail involvement to treatment
- collect safety data |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male patients, or females patients if post menopausal as desribed in protocol section 7.4.1, or hysterectomized, or bilaterally ovarectomized or if pre-menopausal and willing to use at least 1 but preferrably 2 methods of contraception under supervision of the investigator or a gynecologist
2. Aged 18 to 75 years
3. Patients with PPP for at least 6 months, with or without psoriasis lesions on other areas of the skin
4. A PPPASI score of at least 8 with involvement of at lest 10% of the palms and/or the soles
5. Refractory to standard topical therapy
6. Written informed consent provided |
|
E.4 | Principal exclusion criteria |
1. Patients unable to comply with the requirements of the study
2. Female patients who are pregnant or who plan to become pregnant or who are breastfeeding
3. Female patients of childbearing potential who cannot use or will not commit to using at least 1 but preferrably 2 effective forms of contraception simultaneously under supervision of the investigator or a gynecologist
4. Patients whose disease is adequately controlled by standard non-medicated therapy (skin moisturizing and protection) and standard topical corticosteriod therapy, but whose disease has relapsed following discontinuation of these treatments
5. Patients with known hypersensitivity to other retinoids or Vitamin A derivatives, or to any study medication component, especially soybean oil and partially hydrogenated soybean oil
6. Patients treated with any of the following treatments 4 weeks before the start of the study treatment
a) systemic drugs: corticosteroids, immunosuppressants, methotrexate
b) phototherapy: ultraviolet B light therapy (UVB), Psoralen with ultraviolet A combination therapy (PUVA), Grenz rays, X-rays
7. Patients treated with biologic treatment within 12 weeks prior to the start of study treatment
8. Patients treated with any systemic or topical retinoids within 1 year or 1 month, respectively, before start of study treatment, and patients who received systemic retinoids for treatment for PPP at any time
9. Patients with severe generalised pustular psoriasis
10. Patient has a skin condition of palms and / or soles assessed as unrelated to PPP by the investigator
11. Patients with any serious medical condition which, in the opinion of the investigator, may interfere with the safety of the patient
12. Patients with hepatic insufficiency, severe renal failure, uncontrolled hypercholesterolemia, uncontrolled as characterized by:
a. AST / ALT > 2.5 x ULN
b. Creatinine Clearance < 60ml/min (calc. Cockcroft Gault)
c. Fasting triglyceridemia > 1.5 x ULN
d. Fasting cholesterol >1.5 x ULN
e. fasting LDL cholesterol > 1.5x ULN
13. Patients with hypothyroidism as indicated by TSH above ULN and T4 test below LLN or hypervitaminosis A
14. Patients with unstable cardiac disease or poorly controlled cardiovascular risk factors, i.e.:
a) acute coronary syndrome or coronary revascularization (PCI, CABG) within 3 months before start of study treatment
b) poorly controlled diabetes mellitus (HbA1c > 8.5%)
c) systolica blood pressure >= 16-0 mmHg and/or diastolic blood pressure >= 100mmHg at the screening examination
15. Patients receiving drugs with a potential for drug-drug interactions, such as systemic tetracyclines, ketoconazole, St Johns Wort within 1 week, or receiving systemic itraconazole within 2 weeks, before the start of study treatment
16. Patients included in the study of an investigational drug within 2 months before start of study treatment (3 months for biologics)
17. Patients with a score of 20 or more on CES-D or active major psychiatric disorder (e.g. Major Depressive Disorder, Generalized Anxiety Disorder, Biopolar Disorder (I or II), or schizophrenia |
|
E.5 End points |
E.5.1 | Primary end point(s) |
PPPASI - calculated for palm or sole. range from 0 (no PPP) to 72 (most severe PPP)
assesses erythema, number of pustules, desquamation and area involved.
Pustule count - palms and soles
Modified Psoriasis Area Severity Index (mPASI) - psoriatic plaques will be evaluated for redness, thickness and scaliness over 4 body regions - head, upper extremities, trunk and lower extremities
Nail Psorisasis Serverity Index (NAPSI) - taken for finger nails only |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
To assess the response of pustular lesions to total pustule count
To assess the response to psoriasis lesions in locations other than the hands to the treatment
To assess the response of nail involvement to the treatment
To collect safety data for alitretinoin |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 24 or last visit on treatment |
|
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | No |
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 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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |