E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with mild to moderate chronic plaque psoriasis |
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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 efficacy of 1 % LAS 37779 cream once and twice daily during 4 weeks compared to vehicle, in patients with chronic plaque psoriasis. |
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E.2.2 | Secondary objectives of the trial |
To determine the onset of action, the duration of effect and whether rebound is induced in an 8-week single-blind evaluator-blinded follow-up period after stopping the treatment. To assess the safety and tolerability of 1 % LAS 37779 cream compared to vehicle. To investigate the systemic drug and metabolite levels of 1 % LAS 37779 cream after single and repeated cutaneous applications in this population of patients. As an additional and explorative objective, an assessment will be made whether or not clinical improvement goes along with changes in lesion histomorphology, immunochemistry and gene expression of the psoriatic phenotype. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Males and non-pregnant, non-lactating females aged 18 to 65 years, both inclusive. Women of childbearing potential are allowed to enter the trial ONLY if they use medically approved (i.e., mechanical or pharmacological ) contraceptive measures. A female is considered to be of childbearing potential unless she is hysterectomised or at least one year post-menopausal or has undergone tubal ligation. All women of childbearing potential must have a negative pregnancy test at screening visit. 2. Patients who are eligible and able to participate in the trial and who consent to do so in writing after the purpose and nature of the investigation have been explained to them. 3. Patients with a confirmed clinical diagnosis of stable plaque (or vulgaris) psoriasis comprising between 3 % and 30 % of body surface area, provided there are two comparable symmetrical bilateral areas between 20 and 200 cm2. 4. Patients with a comparable baseline Total Sign Score (sum score for erythema, induration and scaling) of at least 6 of 12 for each of the treated areas. 5. Patients in good general condition as confirmed by medical history, physical examination, vital signs measurements, ECG recording and laboratory testing. 6. Patients not willing to use antipsoriatic therapies for the duration of the trial, except for emollients used outside the treated areas. |
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E.4 | Principal exclusion criteria |
1. Patients with pustular, erythrodermic, exfoliative, inverse or guttate psoriasis and/or psoriatic arthritis. 2. Patients with spontaneously/rapidly improving or rapidly deteriorating plaque psoriasis. 3. Patients who have received phototherapy, photochemical (PUVA) therapy or systemic antipsoriatic therapy, such as, but not limited to, corticosteroids, retinoids, vitamin D3 analogues, or immunosuppressive agents (methotrexate, cyclosporine) within 4 weeks before the first trial treatment at Visit 1. 4. Patients who have received any topical antipsoriatic agents such as, but not limited to, corticosteroids, vitamin D3 analogues, salicylates, anthralin, and emollients, within the 2 weeks before the first trial treatment at Visit 1. Use of emollients outside the target lesions will be permitted, provided that the concentration, frequency and quantity throughout the trial are kept similar to those used prior to trial entry. 5. Patients who have received any research medication within the 8 weeks before trial entry at the Screening Visit. 6. Patients under treatment with drugs that might worsen psoriasis, such as lithium or beta-adrenergic antagonists. 7. Patients who have received prolonged sun exposure of the target lesions within 4 weeks before the first trial treatment at Visit 1 or who intend to have prolonged sun exposure of the target lesions during the trial, which is likely to modify the subject’s disease. 8. Patients with a history of opportunistic infections, including skin infections, that might interfere with the trial objectives within 6 months prior to the Screening Visit. 9. Patients who have known clinically significant abnormal hepatic and/or renal function. 10. Patients known to be hypersensitive to the trial medication or any of its components. 11. Patients with disease states or physical conditions that would impair evaluation of the test therapy. Such disease states include, but are not limited to, AIDS or infection with HIV, and autoimmune diseases. 12. Patients with any serious or uncontrolled physical or mental dysfunction at the discretion of the investigator which could place the patient at higher risk derived from his/her participation into the trial, could confound the results of it or is likely to prevent the patient from complying with the requirements of the trial or completing the treatment period. 13. Patients with a history of drug abuse or continuous alcohol consumption that may prevent compliance with trial procedures. 14. Patients unlikely to be co-operative, to take their medication, to complete their Diary Card or to attend the clinic at the required time in the morning.
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E.5 End points |
E.5.1 | Primary end point(s) |
Main variable: Change from baseline in the Total Sign Score of each treated area at the end of treatment (Day 28). Total Sign Score is defined as the sum of individual scores for erythema, induration and scaling [score 0 (absent) to 4 (very severe) for each sign].
Secondary variables: Efficacy: - Change from baseline in the Total Sign Score of each treated area at Days 7, 14, and 21 of treatment and at Days 14, 28, 42 and 56 after stopping treatment. - Change from baseline in the score for each individual sign (erythema, induration and scaling) of each treated area at Days 7, 14, 21 and 28 of treatment and at Days 14, 28, 42 and 56 after stopping treatment. - Percentage of treated areas with an Investigator's Global Assessment of Treatment Response rated as 50 %, 75 %, 90 % and 100 % clear at Days 7, 14, 21 and 28 of treatment and at Days 14, 28, 42 and 56 after stopping treatment. - Percentage of treated areas reaching a 50 % or 75% decrease from baseline in Total Sign Score at Days 7, 14, 21 and 28 of treatment and at Days 14, 28, 42 and 56 after stopping treatment. - Time to reach a 50 % or 75 % reduction from baseline in Total Sign Score (onset of action). - Duration of time with a 50 % or 75 % reduction from baseline in Total Sign Score after stopping treatment (duration of action). - Percentage of treated areas with a loss of half of Total Sign Score improvement achieved at Day 28 of treatment and at Days 14, 28, 42 and 56 after stopping treatment. - Percentage of treated areas reaching 125 % of baseline Total Sign Score at Days 14, 28, 42 and 56 after stopping treatment (rebound effect).
Histomorphology, immunochemistry and gene expression: Changes in these 3 above mentioned items of punch biopsies of treated lesional areas taken at baseline and Day 28 of treatment. - Histological phenotype, epidermal thickness, quality and quantity of the inflammatory infiltrate, architecture of the papillary blood vessels, papillomatosis, perifocal and epidermal reactions. - Qualitative description of the inflammatory cell infiltrate, reactions with different monoclonal antibodies directed to antigens CD1a, CD3, CD4, CD8, CD25, CD31, CD54, HLA-DR, filaggrin, involucrin, keratin-16 and Ki-67. - RNA analysis: elafin, psoriasin, K16, ICAM-1, IFN-g, IL-2, IL-7R, IL-7, IL-8, IL-12(p40), IL-23(p19), IL-12(p35), IL-15, IL-17, IL-19, IL-20, TNF-a, STAT-1, STAT-3, TRIM22, IP-10, IRF-1, RANTES, CTLA-4, IL For this purpose punch biopsies will be obtained from a maximum of twenty patients.
Plasma levels of LAS 37779 and its metabolites: Plasma levels and pharmacokinetic parameters will be determined after single (Day 1 of treatment) and repeated application (Day 28 of treatment). At days 7, 14 and 21 of treatment, plasma drug levels will be determined before IMP morning application. A maximum of thirty-two patients will be included for this purpose.
Safety and tolerability: Adverse events recorded during the treatment and follow-up phases, including laboratory evaluations, vital signs and 12-lead ECG and Global Assessment of Tolerability.
Other variables: Number of withdrawals and reasons for withdrawal.
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
intraindividual comparison |
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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 | 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 | 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 | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |