Efficacy and Safety of LEO 19123 Cream in the Treatment of Psoriasis Vulgaris

Study Overview
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Brief Summary
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This study will compare the efficacy and safety of once daily treatment of LEO 19123 cream versus Dovonex® cream (applied twice daily) and versus LEO 19123 cream vehicle alone (applied twice daily) in subjects with psoriasis vulgaris. Subject will be treated for 4 weeks. All subjects will apply LEO 19123 cream to psoriasis lesions on the left or right side of the body and either Dovonex® cream or cream vehicle to lesions on the other side.

Official Title
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LEO 19123 Cream in the Treatment of Psoriasis Vulgaris

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: LEO 19123 Cream (calcipotriol plus LEO 80122)
* Drug: Dovonex® cream
* Drug: Cream vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent to be obtained prior to any trial related procedure, including washout. Clinical diagnosis of psoriasis vulgaris involving trunk and/or arms and/or legs with a symmetrical distribution amenable to treatment with a maximum of 50 g/week of topical medication on each side of the body. At Visit 1, there should not be a difference between the right and left side of more than 1 for each of the PASI criteria (redness, thickness and scaliness). A minimum PASI score for extent of 2 on each side in at least one body region (i.e. psoriasis affecting at least 10% of left and right arm, and/or 10% of left and right side of the trunk, and/or 10% of left and right leg). Disease severity graded mild, moderate, severe or very severe according to the Investigator's global assessment (IGA) of disease severity on each side of the body. The assessment should be the same for both sides of the body. Age 18 years or above Male subjects, or females of non-childbearing potential (i.e. surgically sterile or at least two years postmenopausal) Attending a hospital outpatient clinic or the private practice of a dermatologist Exclusion Criteria: Subjects using systemic treatments with biological therapies with a possible effect on psoriasis vulgaris within 12 weeks prior to randomisation (e.g. alefacept, efalizumab, etanercept, infliximab, adalimumab) Systemic treatment with all other therapies, besides biologics, with a possible effect on psoriasis vulgaris (e.g., corticosteroids, retinoids, immunosuppressants) within 4 weeks prior to randomisation (inhaled or intranasal steroids for asthma or rhinitis may be used) PUVA or Grenz ray therapy within 4 weeks prior to randomisation UVB therapy within 2 weeks prior to randomisation Any topical treatment (except for emollients) of the trunk/limbs (except on flexures) within 2 weeks prior to randomisation Topical treatment for other relevant skin disorders on the face and flexures (e.g., facial and flexural psoriasis, eczema) with potent or very potent (WHO group III-IV) corticosteroids, vitamin D analogues or retinoids within 2 weeks prior to randomisation Topical treatment for other relevant skin disorders on the scalp (e.g. scalp psoriasis) with very potent (WHO group IV) corticosteroids, vitamin D analogues or retinoids within 2 weeks prior to randomisation Planned initiation of, or changes to concomitant medication that could affect psoriasis vulgaris (e.g., beta blockers, ACE inhibitors, anti-malaria drugs, lithium) within 2 weeks prior to randomisation Subjects who have received treatment with any non-marketed drug substance (i.e., an agent which has not yet been made available for clinical use following registration) within the 4-week period prior to randomisation Subjects with current participation in any other interventional clinical trial Subjects with any of the following conditions present on the treatment area: eczematous skin, atopic dermatitis, clinical infection, ulcers and wounds Subjects with a history of serious allergy, allergic skin rash or sensitivity to any component of the investigational products or formulations being tested Subjects with positive hepatitis B, C or HIV Known or suspected severe renal insufficiency or severe hepatic disorders Known or suspected disorders of calcium metabolism associated with hypercalcaemia Current diagnosis of erythrodermic, exfoliative, guttate or pustular psoriasis Planned exposure to the sun during the study that may affect psoriasis vulgaris (i.e., normal lifestyle outdoor activities are permitted but deliberate exposure to sunlight or artificial ultraviolet light should be avoided)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: LEO 19123 Cream (calcipotriol plus LEO 80122)<br>* Once daily application<br>|
| Active Comparator: 2<br> | Drug: Dovonex® cream<br>* Twice daily application<br>|
| Placebo Comparator: 3<br> | Drug: Cream vehicle<br>* Twice daily application<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage Change in PASI (Psoriasis Area Severity Index) | The following formula was used to calculate the PASI for each side of the body: Upper extremities: 0.2 (R + T+ S) E = X Trunk: 0.3 (R + T+ S) E = Y Lower extremities 0.4 (R + T+ S) E = Z where: R = score for redness T = score for thickness S = score for scaliness E = score for extent The sum of X + Y + Z gives the total PASI, which can range from 0 to 64.8. The PASI used in this study is modified to exclude assessment of the head, as study treatment was not used here. | From baseline (Day 0) to end of treatment (Day 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator's Global Assessment of Disease Severity | At all visits the (sub)investigator made a global assessment of the disease severity for psoriasis on the left and right side, respectively, of the body by use of the 6-point scale below. These assessments were to represent the average lesion severity on the left and right side, respectively. These assessments were to be based on the condition of the disease at the time of evaluation, and not in relation to the condition at a previous visit. Clear Almost clear Mild Moderate Severe Very severe | At end of treatment (Day 28) | 
| Participants With Controlled Disease According to the Investigator's Global Assessment of Disease Severity | For subjects with a baseline (Visit 1) severity of moderate or worse, controlled disease is defined as clear or almost clear according to the Investigator's global assessment of disease severity. For subjects with a baseline (Visit 1) severity of mild, controlled disease is defined as clear according to the Investigator's global assessment of disease severity. | At end of treatment (Day 28) | 
| Participant's Overall Assessment of Treatment Response | The participant assessed the treatment response by use of the 6-point scale below. Worse Unchanged Slight improvement Moderate improvement Marked improvement Almost clear Cleared | At end of treatment (Day 28) | 
| Participant's Assessment of Treatment Preference |  | At end of treatment (Day 28) | 
| Participants With at Least 75% Reduction in PASI (PASI 75) |  | From baseline (Day 0) to end of treatment (Day 28) | 
| Participants With at Least 50% Reduction in PASI (PASI 50) |  | From baseline (Day 0) to end of treatment (day 28) | 
| The Absolute Change in PASI (Psoriasis Area Severity Index) | The following formula was used to calculate the PASI for each side of the body: Upper extremities: 0.2 (R + T+ S) E = X Trunk: 0.3 (R + T+ S) E = Y Lower extremities 0.4 (R + T+ S) E = Z where: R = score for redness T = score for thickness S = score for scaliness E = score for extent The sum of X + Y + Z gives the total PASI, which can range from 0 to 64.8. The PASI used in this study is modified to exclude assessment of the head, as study treatment was not used here. | From baseline to end of treatment (Day 28) |