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 | 16.0 |
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. A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea and a follicle-stimulating hormone concentration of 40 international units (IU)/L.
• Child-bearing potential with negative pregnancy test as determined by a human
chorionic gonadotropin (hCG) test at screening or prior to dosing and either 1) agrees to use a medically acceptable contraception method for an appropriate
period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point and continue contraception until the end of the study, or 2) has only same-sex partners, when this is her preferred and usual lifestyle.
2. Capable of understanding and willing to provide signed and dated written voluntary
informed consent (and any local or national authorization requirements) before any protocol specific procedures are performed.
3. Male or female aged at least 18 years at time of consent and at time of first dose.
4. Have PPP for at least 6 months, with or without psoriasis lesions on other areas of
the skin.
5. A PPPASI score of at least 8 with involvement of at least 10% of the palms and/or the soles.
6. Refractory to standard topical corticosteroid therapy. |
|
E.4 | Principal exclusion criteria |
1. Unable to comply with the requirement of the study.
2. Female subjects who are pregnant or who plan to become pregnant or who are breast feeding.
3. Subjects whose disease is adequately controlled by standard non-medicated therapy (skin moisturizing and protection).
4. Known hypersensitivity to other retinoids or vitamin A derivatives, or to any study medication component, especially soybean oil and partly hydrogenated soybean oil.
5. Treated with any of the following treatments 4 weeks before the start of study treatment:
• systemic drugs: corticosteroids, immunosuppressants, methotrexate
• phototherapy: ultraviolet B light therapy [UVB], psoralen with ultraviolet A
combination therapy [PUVA], Grenz rays, X-rays
6. Treated with biologic treatments within 6 weeks prior to start of study treatment.
7. Abnormal hematology.
8. Treated with any systemic or topical retinoids within 3 months or 1 month,
respectively, before start of study treatment.
9. Treated with high-potency topical corticosteroids within 2 weeks before the start of study treatment.
10. Severe generalized pustular psoriasis.
11. A skin condition of palms and/or soles that interferes with the diagnosis of PPP by
the investigator.
12. Any condition that, in the judgment of the investigator, would put the subject at
unacceptable risk for participation in the study.
13. Hepatic insufficiency, severe renal failure, uncontrolled hypercholesterolemia as characterized by:
• AST/ ALT > 2.5 x upper limit of normal (ULN)
• Creatinine clearance <60 mL/min (calculated, Cockcroft-Gault)
• Fasting triglyceridemia > 1.5 x ULN
• Fasting cholesterol > 1.5 x ULN
• Fasting low-density lipoprotein (LDL) cholesterol > 1.5x ULN
14. Subjects with hypothyroidism as indicated by TSH above ULN and T4 test below LLN or hypervitaminosis A.
15. Subjects with unstable cardiac disease or poorly controlled cardiovascular risk
factors, for example:
• Acute coronary syndrome or coronary revascularization (PCI, CABG) within 3
months before start of study treatment
• Poorly controlled diabetes mellitus (HbA1c > 8.5%)
16. Systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg at
the screening examination.
17. Subjects receiving drugs with a potential for drug-drug interaction, such as systemic tetracyclines, ketoconazole, or St. John’s Wort within 1 Week, or receiving systemic itraconazole within 2 Weeks, before start of study treatment.
18. Subjects included in the study of an investigational drug within 2 months before start of study treatment (3 months for biologics).
19. Subjects with a score of 20 or more on CES-D, or with active major psychiatric
disorder (eg, Major Depressive Disorder, Generalized Anxiety Disorder, Bipolar
Disorder [I or II], or schizophrenia).
20. Subjects who score a 4 or 5 during the previous 30 days on the CSSRS at Screening or Baseline.
21. Subjects who have made a suicide attempt within the 6 months preceding the
Screening or Baseline visits. |
|
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, truck 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
| 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | 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 |