| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Plaque-type psoriasis (psoriasis vulgaris) for at least 6 months |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10050576 |
| E.1.2 | Term | Psoriasis vulgaris |
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| 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 |
| Primary objective is to gain evidence of the efficacy of three distinct combinations of Betamethason dipropionate and Bexaroten in different concentrations compared to Placebo and Daivobet®-ointment in the treatment of Plaque-Type Psoriasis assessed by the AUC of the width of the echo-lucent band located at the dermo-epidermal junction as measured by sonography at visit 1, 4, 8 and 11. |
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| E.2.2 | Secondary objectives of the trial |
Secondary objective is to evaluate the efficacy assessed by means of the following symptoms: scaling, erythema and induration of the test areas. In addition, a total score (sum score of these three symptoms) is evaluated. All scores are analyzed by displaying the development during the study over time and by the percentage of change at visit 11 compared to baseline.
Further secondary endpoints are the development and the percentage change of the width of the echolucent band over time, the tolerability of the formulations as measured by a physicians’ assessment of tolerability at visit 4, 8 and at the end of the study, the erythema and telangiectasia scores at visit 2 to 10 and to evaluate the safety as assessed by incidence and severity of AEs and SAEs and their relationship to the study medications.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion Criteria
• Male or female patients between 18 and 75 years of age with a diagnosis of stable plaque-type psoriasis (psoriasis vulgaris) for at least 6 month
• Psoriasis plaques that are suitable to be defined as target area lesions by the following criteria:
o Psoriasis plaques must be located at trunk and/or extremities. Plaques that are located on the head (incl. scalp), palms, sole of the feet, intertriginous or genitoanal areas are not suitable as target areas
o Comparable psoriasis plaques with at least “2” in each score (Range 0-4) for the three distinct symptoms scaling; erythema; and induration
o No more than 3 points difference in total score (= sum of scores for scaling, erythema and induration; range 0-12) of the chosen comparable psoriasis plaques
o Enough psoriatic surface area to define 5 clearly distinguishable (minimum distance between test areas: 1 cm) test areas of at least 1 cm² plaque size
• Patient is willing and able to comply with the requirements of the clinical study protocol. In particular, patient must adhere to concomitant therapy prohibitions of the test areas and must agree to avoid intense UV exposure of the test areas during the study
• Written informed consent to participate in the study, prior to any study related procedures, indicating an understanding of the purpose of the study
• A patient of childbearing potential agrees to use one of the following highly effective contraceptive methods for the duration of the study and the following 4 weeks after study drug discontinuation:
o Combined oral, implanted or injectable contraceptives on a stable dose for at least 3 months prior to study entrance, OR
o Partner who has been sterilized by vasectomy for at least 3 months prior to study entry, OR
o Intrauterine devices (IUD) inserted for at least 4 weeks prior to study entrance, AND
o Barrier methods (e.g. condom, cervical caps, diaphragm)
Note: The investigator must inform all female patients of childbearing potential that bexarotene can potentially induce metabolic enzymes and thereby theoretically reduce the efficacy of oestroprogestative contraceptives.
• Male patients with sexual partners who are pregnant, possibly pregnant, or who could become pregnant must use condoms during sexual intercourse for the duration of the study and for at least 4 weeks after the last dose of drug.
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| E.4 | Principal exclusion criteria |
• Too few body surface area covered with psoriasis plaques that meet the specified inclusion criteria to be defined as 5 clearly distinguishable test areas
• Any condition that may interfere with the study assessments or sonographic measurements of the skin and/or may have an influence on skin immune response (incl. open wounds)
• Known adverse reactions of any severity or hypersensitivity to any ingredient of the test products or other retinoid
• No willingness to avoid induction of heavy sweating, e.g. due to sauna visits, excessive sports activities during the study course
• No willingness to avoid swimming, bathing or wetting of the designated test areas between visits
• Pregnant or breast-feeding women
• A medical condition that may put the patient at a general risk and therefore would prevent participation in the clinical trial (including but not limited to: infectious diseases, major surgery within the last 4 weeks, coronary artery disease, renal impairment, hepatic impairment, uncontrolled metabolic diseases, disorders of the calcium metabolism, autoimmune diseases)
• Significant skin diseases other than plaque-type psoriasis (psoriasis vulgaris), including but not limited to: skin diseases in consequence of tuberculosis or syphilis, rosacea, perioral dermatitis, acne vulgaris, dermatrophy, striae distensae, increased fragility of skin blood vessels, ichthyosis, ulcers, wounds,pruritus and reaction after vaccination
• Skin infections (including but not limited to: herpes, varicella, mycotic skin infections, bacterial skin infections or parasitic skin infections)
• History or presence of malignant disease (other than surgically removed basal cell carcinoma) and/or auto immune diseases
• Current diagnosis of guttate, erythrodermic or pustular psoriasis
• Patients who did not respect the following wash-out periods prior to study entry or do not restrain from using one of the following treatments during the study:
Treatment Wash out period
Topical treatment in the test area
Any topical anti-psoriatic drug 2 weeks
Systemic treatment
Biologics 6 months
Any other systemic antipsoriatic treatment (corticosteroids, ciclosporin, MTX, fumaric acid esters) 3 months
Procedures
Phototherapy or artificial ultraviolet light 4 weeks
• Excessive sunlight exposure within 28 days prior to study entry and during the conduct of the study
• Usage of any topical formulation (incl. cosmetics, emollients, etc) on the designated target areas during the course of the study
• Vitamin A intake > 15,000 IU/day
• Vaccination 6 days prior to enrolment or during the study
• Subjects who are – in the opinion of the investigator – unreliable, and/or non-compliant, and/or who present with any condition or treatment (including cosmetic products) that may interfere with psoriasis or the conduct of the trial
• Participation in any other clinical trial within 30 days prior or during this trial
• Subject is an adult under guardianship, hospitalised, deprived of freedom or unable to communicate or cooperate with the investigator due to language or mental problems
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| E.5 End points |
| E.5.1 | Primary end point(s) |
In the present exploratory study no sample size calculation has been performed. The sample size has been determined from the clinician’s perspective. The number of 20 evaluable subjects (recruitment of 22 subjects) is based on the clinical assumption of how many subjects are needed to gain first evidence of efficacy and safety of the IMPs.
The primary endpoint is the AUC of width of the echo-lucent band located at the dermo-epidermal junction (representing the combination of acanthotic epidermal thickening and inflammation in psoriasis) as measured by sonography at visit 1, 4, 8 and 11. |
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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 | Yes |
| 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 | 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) | Yes |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| 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 | 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
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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 | 0 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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