Psoriasis Vulgaris
Conditions
Brief summary
The purpose is to compare the efficacy of treatment with LEO 90100 at Week 4 to that of calcipotriol plus betamethasone dipropionate (BDP) gel at Week 8 in subjects with psoriasis vulgaris
Interventions
Sponsors
LEO Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or above * Psoriasis vulgaris on the trunk and/or limbs (excluding psoriasis on the genitals and skin folds) involving 2-30% of the Body Surface Area (BSA) * A Physician's Global Assessment of disease severity (PGA) of at least mild on trunk and limbs * A modified Psoriasis Area Severity Index (PASI) score of at least 2 on the trunk and limbs.
Exclusion criteria
* Current diagnosis of guttate, erythrodermic, exfoliative or pustular psoriasis * Systemic treatment with biological therapies, whether marketed or not, with a possible effect on psoriasis vulgaris within the following time periods prior to randomisation: * etanercept - within 4 weeks prior to randomisation * adalimumab, infliximab - within 8 weeks prior to randomisation * ustekinumab - within 16 weeks prior to randomisation * other products - within 4 weeks/5 half-lives prior to randomisation (whichever is longer) * Systemic treatment with all other therapies with a possible effect on psoriasis vulgaris (e.g. corticosteroids, retinoids, methotrexate, ciclosporin and other immunosuppressants within 4 weeks prior to randomisation) * Subjects who have received treatment with any non-marketed drug substance (i.e. a drug which has not yet been made available for clinical use following registration) within 4 weeks/5 half-lives (whichever is longer) prior to randomisation. * Psoralen combined with Ultraviolet A (PUVA) therapy within 4 weeks prior to randomisation * Ultraviolet B (UVB) therapy within 2 weeks prior to randomisation * Topical anti-psoriatic treatment on the trunk and limbs (except for emollients) within 2 weeks prior to randomisation * Topical treatment on the face, scalp and skin folds with corticosteroids, vitamin D analogues or prescription shampoos within 2 weeks prior to randomisation * Females who are pregnant, wishing to become pregnant during the trial or are breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Success According to the PGA | 4 Weeks for LEO 90100 and 8 weeks for calcipotriol BDP gel | To compare the efficacy of treatment of LEO 90100 at Week 4 to that of calcipotriol BDP gel at Week 8 in subjects with psoriasis vulgaris. Five-point assessment (clear, almost clear, mild, moderate, and severe) was made for the severity of psoriasis vulgaris on the trunk and limbs at all on-treatment visits using Physician's Global Assessment of Disease Severity (PGA). 'Treatment success' was defined as achieving 'clear' or 'almost clear' for subjects with at least 'moderate' disease at baseline and 'clear' for subjects with 'mild' disease at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjects With PASI 75 at Week 4 for LEO 90100 and at Week 8 for Calcipotriol BDP Gel. | Week 4 for LEO 90100; Week 8 for calcipotriol BDP gel | Subjects with PASI 75 (a 75% reduction in the modified Psoriasis Area and Severity Index) at Week 4 for LEO 90100 and at Week 8 for calcipotriol BDP gel. |
| Time to 'Treatment Success' According to PGA. | From Baseline to Week 12 | Time to treatment success was calculated as the number of weeks from baseline to the visit where the subject first achieved treatment success. 'Treatment success' was defined as achieving 'clear' or 'almost clear' for subjects with at least 'moderate' disease at baseline and 'clear' for subjects with 'mild' disease at baseline. |
| Change in Itch as Assessed on a VAS Scale (LEO 90100 vs. the Foam Vehicle Group). | Baseline to Week 4 | Maximum itch during the previous 24 hours was assessed on a Visual Analogue Scale (VAS) - range from 0 (no itch at all) to 100 mm (worst itch one could imagine). |
| Change in Itch as Assessed on a VAS Scale From Baseline to Week 4 (LEO 90100) vs. Week 8 (Calcipotriol BDP Gel). | Baseline to Week 4; Baseline to Week 8 | Maximum itch during the previous 24 hours was assessed on a Visual Analogue Scale - range from 0 (no itch at all) to 100 mm (worst itch one could imagine). |
Countries
France
Participant flow
Recruitment details
First Subject First Visit: 30-Jun-2014 Last Subject Last Visit: 04-Mar-2015
Pre-assignment details
A total of 504 subjects were enrolled, 41 enrolled subjects were not randomised. 463 subjects were randomised as follows: 185 subjects to LEO 90100, 188 to calcipotriol BDP gel, 47 to foam vehicle, and 43 to gel vehicle
Participants by arm
| Arm | Count |
|---|---|
| LEO 90100 LEO 90100 aerosol foam, containing calcipotriol (as hydrate) 50 mcg/g and betamethasone 0.5 mg/g (as dipropionate), 60 g per can, applied once daily up to 12 weeks
LEO 90100 aerosol foam | 185 |
| Aerosol Foam Vehicle Aerosol foam vehicle, 60 g per can, applied once daily for up to 12 weeks
Aerosol foam vehicle | 47 |
| Calcipotriol BDP Gel Calcipotriol BDP gel, containing calcipotriol (as hydrate) 50 mcg/g and betamethasone 0.5 mg/g (as dipropionate), 60 g per bottle, applied once daily up to 12 weeks
Calcipotriol BDP gel | 188 |
| Gel Vehicle Gel vehicle, 60 g per bottle, applied once daily up to 12 weeks
Gel vehicle | 43 |
| Total | 463 |
Baseline characteristics
| Characteristic | LEO 90100 | Aerosol Foam Vehicle | Calcipotriol BDP Gel | Gel Vehicle | Total |
|---|---|---|---|---|---|
| Age, Continuous | 54.0 years STANDARD_DEVIATION 14.5 | 54.6 years STANDARD_DEVIATION 14.2 | 54.5 years STANDARD_DEVIATION 14.9 | 51.9 years STANDARD_DEVIATION 15.5 | 54.1 years STANDARD_DEVIATION 14.7 |
| Sex: Female, Male Female | 59 Participants | 18 Participants | 74 Participants | 17 Participants | 168 Participants |
| Sex: Female, Male Male | 126 Participants | 29 Participants | 114 Participants | 26 Participants | 295 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 62 / 185 | 25 / 47 | 60 / 188 | 28 / 43 |
| serious Total, serious adverse events | 4 / 185 | 0 / 47 | 3 / 188 | 1 / 43 |
Outcome results
Primary
Treatment Success According to the PGA
To compare the efficacy of treatment of LEO 90100 at Week 4 to that of calcipotriol BDP gel at Week 8 in subjects with psoriasis vulgaris. Five-point assessment (clear, almost clear, mild, moderate, and severe) was made for the severity of psoriasis vulgaris on the trunk and limbs at all on-treatment visits using Physician's Global Assessment of Disease Severity (PGA). 'Treatment success' was defined as achieving 'clear' or 'almost clear' for subjects with at least 'moderate' disease at baseline and 'clear' for subjects with 'mild' disease at baseline.
Time frame: 4 Weeks for LEO 90100 and 8 weeks for calcipotriol BDP gel
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LEO 90100 | Treatment Success According to the PGA | 38.3 percentage of subjects |
| Calcipotriol BDP Gel | Treatment Success According to the PGA | 22.5 percentage of subjects |
Comparison: Mantel-Haenszel odds of treatment success in LEO 90100 group relative to calcipotriol BDP gel group, adjusted for pooled centre and baseline PGA.~Multiple imputation was used to handle missing PGA values.p-value: <0.00195% CI: [1.46, 4.46]Mantel Haenszel
Secondary
Change in Itch as Assessed on a VAS Scale From Baseline to Week 4 (LEO 90100) vs. Week 8 (Calcipotriol BDP Gel).
Maximum itch during the previous 24 hours was assessed on a Visual Analogue Scale - range from 0 (no itch at all) to 100 mm (worst itch one could imagine).
Time frame: Baseline to Week 4; Baseline to Week 8
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LEO 90100 | Change in Itch as Assessed on a VAS Scale From Baseline to Week 4 (LEO 90100) vs. Week 8 (Calcipotriol BDP Gel). | -30.5 units on a scale |
| Calcipotriol BDP Gel | Change in Itch as Assessed on a VAS Scale From Baseline to Week 4 (LEO 90100) vs. Week 8 (Calcipotriol BDP Gel). | -28.5 units on a scale |
Comparison: Mean change in itch adjusted for pooled centre, baseline PGA and baseline itch. Multiple imputation used for missing data.p-value: =0.33ANCOVA
Secondary
Change in Itch as Assessed on a VAS Scale (LEO 90100 vs. the Foam Vehicle Group).
Maximum itch during the previous 24 hours was assessed on a Visual Analogue Scale (VAS) - range from 0 (no itch at all) to 100 mm (worst itch one could imagine).
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LEO 90100 | Change in Itch as Assessed on a VAS Scale (LEO 90100 vs. the Foam Vehicle Group). | -30.5 units on a scale |
| Calcipotriol BDP Gel | Change in Itch as Assessed on a VAS Scale (LEO 90100 vs. the Foam Vehicle Group). | -15.9 units on a scale |
Comparison: Mean change in itch adjusted for pooled centre, baseline PGA and baseline itch. Multiple imputation used for missing data.p-value: <0.001ANCOVA
Secondary
Subjects With PASI 75 at Week 4 for LEO 90100 and at Week 8 for Calcipotriol BDP Gel.
Subjects with PASI 75 (a 75% reduction in the modified Psoriasis Area and Severity Index) at Week 4 for LEO 90100 and at Week 8 for calcipotriol BDP gel.
Time frame: Week 4 for LEO 90100; Week 8 for calcipotriol BDP gel
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LEO 90100 | Subjects With PASI 75 at Week 4 for LEO 90100 and at Week 8 for Calcipotriol BDP Gel. | 52.1 percentage of subjects |
| Calcipotriol BDP Gel | Subjects With PASI 75 at Week 4 for LEO 90100 and at Week 8 for Calcipotriol BDP Gel. | 34.6 percentage of subjects |
Comparison: Mantel-Haenszel odds of having PASI 75 in LEO 90100 group relative to calcipotriol BDP gel group, adjusted for pooled centre and baseline PGA.~Multiple imputation was used to handle missing data.p-value: =0.00195% CI: [1.37, 3.47]Mantel Haenszel
Secondary
Time to 'Treatment Success' According to PGA.
Time to treatment success was calculated as the number of weeks from baseline to the visit where the subject first achieved treatment success. 'Treatment success' was defined as achieving 'clear' or 'almost clear' for subjects with at least 'moderate' disease at baseline and 'clear' for subjects with 'mild' disease at baseline.
Time frame: From Baseline to Week 12
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LEO 90100 | Time to 'Treatment Success' According to PGA. | 6 weeks |
| Calcipotriol BDP Gel | Time to 'Treatment Success' According to PGA. | NA weeks |
p-value: <0.001Log Rank