Psoriasis Vulgaris
Conditions
Brief summary
A phase 3 trial comparing the efficacy and safety of LEO 90100 aerosol foam with the aerosol foam vehicle used twice weekly as long-term maintenance therapy in subjects with psoriasis vulgaris. A 12-month, international, multi-centre, randomised, vehicle controlled, double-blind, 2-arm, parallel group trial.
Detailed description
After an initial 4-week period of once-daily treatment with open-label active LEO 90100 aerosol foam, subjects who qualify for randomisation will continue into a 52-week maintenance treatment period with twice-weekly application of randomised LEO 90100 aerosol foam / LEO 90100 aerosol foam vehicle. If the subject experiences a relapse of psoriasis, the active lesions will be treated for 4 weeks with open-label active LEO 90100 aerosol foam.
Interventions
LEO 90100 aerosol foam twice weekly
DRUGLEO 90100 aerosol foam vehicle
LEO 90100 aerosol foam vehicle twice weekly
Sponsors
LEO Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A clinical diagnosis of psoriasis vulgaris for at least 6 months involving the trunk and/or limbs, amenable to treatment with maximum of 100 g of trial medication per week * 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 target lesion/target location of at least 3 cm at its longest axis located on the body (i.e., not on the scalp, face or intertriginous areas), scoring at least 1 ('mild') for each of redness, thickness and scaliness, and at least 4 in total by the Investigator's Assessment of Severity of the Target Lesion/Location For subjects participating in hypothalamic-pituitary-adrenal (HPA)-axis testing, furthermore: * An extent of psoriasis vulgaris on trunk and/or limbs of disease severity (PGA) of at least 'moderate' affecting between 10 and 30% of the body surface area (BSA) excluding psoriatic lesions of genitals and skin folds at Visit 1.
Exclusion criteria
* Systemic treatment with biological therapies, whether marketed or not, with a possible effect on psoriasis vulgaris within the following time periods prior to Visit 1: * etanercept - within 4 weeks prior to Visit 1 * adalimumab, infliximab - within 8 weeks prior to Visit 1 * ustekinumab - within 16 weeks prior to Visit 1 * secukinumab - within 12 weeks prior to Visit 1 * other products - within 4 weeks/5 half-lives prior to Visit 1 (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 Visit 1 * Systemic treatment with apremilast within 4 weeks prior to Visit 1 * Psoralen combined with Ultraviolet A (PUVA) therapy within 4 weeks prior to Visit 1 * Ultraviolet B (UVB) therapy within 2 weeks prior to Visit 1 * Severe and/or extensive scalp psoriasis which, in the opinion of the investigator, requires treatment with potent or super-potent corticosteroids which will be prohibited during the trial For subjects participating in HPA-axis testing, furthermore: * Antidepressive medications within 4 weeks prior to Visit 1 or during the trial. Oestrogen therapy (including contraceptives), antidepressant medications and any other medication known to affect cortisol levels or HPA axis integrity within 4 weeks prior to baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Relapse | From Randomisation (Week 4) until first relapse or End of Treatment (Week 56 or early withdrawal) | Time to first relapse (at least 'mild' according to the Physician's Global Assessment of disease severity \[PGA\]). The investigator was to grade the severity of psoriasis of the trunk and limbs using Physician's global assessment of disease severity 5-point scale: Clear = 0; Almost clear = 1; Mild = 2; Moderate = 3; Severe = 4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Days in Remission During the Maintenance Phase | From Randomisation (Week 4) until End of Treatment (Week 56 or early withdrawal) | Remission defined as 'clear' or 'almost clear' according to the PGA. The investigator was to grade using a global assessment of the disease severity of psoriasis of the trunk and limbs using the PGA 5-point scale: Clear = 0; Almost clear = 1; Mild = 2; Moderate = 3; Severe = 4 |
| Number of Relapses During the Maintenance Phase | From Randomisation (Week 4) until End of Treatment (Week 56) | Defined as number of 4-week periods with use of once-daily rescue investigational medicinal product |
Countries
Canada, France, Germany, Poland, United Kingdom, United States
Participant flow
Pre-assignment details
722 subjects were screened of which 650 subjects were assigned to treatment with LEO 90100 open-label phase. Subjects did not progress from screening due to adverse event=1, lost to follow-up=2, other reasons=2, screening failures=52, and withdrawal by subject=15. All 650 subjects were exposed to LEO 90100 during the open-label phase
Participants by arm
| Arm | Count |
|---|---|
| LEO 90100 Open-label Phase LEO 90100, an aerosol foam formulation containing calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate) was applied once daily on the body for 4 weeks. | 650 |
| Total | 650 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Maintenance Phase | Adverse Event | 0 | 2 | 1 |
| Maintenance Phase | Death | 0 | 0 | 1 |
| Maintenance Phase | Lack of Efficacy | 0 | 20 | 16 |
| Maintenance Phase | Lost to Follow-up | 0 | 12 | 14 |
| Maintenance Phase | Not achieve treatment success after Wk 4 | 0 | 3 | 2 |
| Maintenance Phase | Not clear/almost clear after rescue med | 0 | 65 | 70 |
| Maintenance Phase | Other reasons | 0 | 9 | 13 |
| Maintenance Phase | Withdrawal by Subject | 0 | 30 | 36 |
| Open-label Phase | Adverse Event | 2 | 0 | 0 |
| Open-label Phase | Lost to Follow-up | 9 | 0 | 0 |
| Open-label Phase | Other reasons | 9 | 0 | 0 |
| Open-label Phase | Withdrawal by Subject | 7 | 0 | 0 |
Baseline characteristics
| Characteristic | LEO 90100 Open-label Phase |
|---|---|
| Age, Continuous | 51.8 Years STANDARD_DEVIATION 14.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 75 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 568 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants |
| PGA Mild | 83 Participants |
| PGA Moderate | 509 Participants |
| PGA Severe | 58 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 37 Participants |
| Race/Ethnicity, Customized Race Black or African American | 9 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 4 Participants |
| Race/Ethnicity, Customized Race White | 584 Participants |
| Region of Enrollment Canada | 163 participants |
| Region of Enrollment France | 61 participants |
| Region of Enrollment Germany | 59 participants |
| Region of Enrollment Poland | 60 participants |
| Region of Enrollment United Kingdom | 79 participants |
| Region of Enrollment United States | 228 participants |
| Sex: Female, Male Female | 226 Participants |
| Sex: Female, Male Male | 424 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 650 | 0 / 272 | 1 / 273 |
| other Total, other adverse events | 47 / 650 | 83 / 272 | 87 / 273 |
| serious Total, serious adverse events | 4 / 650 | 14 / 272 | 11 / 273 |
Outcome results
Primary
Time to First Relapse
Time to first relapse (at least 'mild' according to the Physician's Global Assessment of disease severity \[PGA\]). The investigator was to grade the severity of psoriasis of the trunk and limbs using Physician's global assessment of disease severity 5-point scale: Clear = 0; Almost clear = 1; Mild = 2; Moderate = 3; Severe = 4
Time frame: From Randomisation (Week 4) until first relapse or End of Treatment (Week 56 or early withdrawal)
Population: Full analysis set: included all subjects randomised who had treatment success at randomisation, defined as PGA score of 'clear' or 'almost clear' with at least a 2-grade improvement from baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LEO 90100 Aerosol Foam | Time to First Relapse | 56 days |
| LEO 90100 Aerosol Foam Vehicle | Time to First Relapse | 30 days |
Comparison: All randomized subjects were considered for statistical analysis.p-value: <0.00195% CI: [0.47, 0.69]Regression, Cox
Secondary
Number of Relapses During the Maintenance Phase
Defined as number of 4-week periods with use of once-daily rescue investigational medicinal product
Time frame: From Randomisation (Week 4) until End of Treatment (Week 56)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LEO 90100 Aerosol Foam | Number of Relapses During the Maintenance Phase | 2.0 relapses | Standard Deviation 1.7 |
| LEO 90100 Aerosol Foam Vehicle | Number of Relapses During the Maintenance Phase | 3.1 relapses | Standard Deviation 2.2 |
p-value: <0.00195% CI: [0.46, 0.63]Poisson regression
Secondary
Proportion of Days in Remission During the Maintenance Phase
Remission defined as 'clear' or 'almost clear' according to the PGA. The investigator was to grade using a global assessment of the disease severity of psoriasis of the trunk and limbs using the PGA 5-point scale: Clear = 0; Almost clear = 1; Mild = 2; Moderate = 3; Severe = 4
Time frame: From Randomisation (Week 4) until End of Treatment (Week 56 or early withdrawal)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LEO 90100 Aerosol Foam | Proportion of Days in Remission During the Maintenance Phase | 70.2 Proportion of days | Standard Deviation 21.7 |
| LEO 90100 Aerosol Foam Vehicle | Proportion of Days in Remission During the Maintenance Phase | 60.8 Proportion of days | Standard Deviation 20.1 |
Comparison: The number of days in remission was calculated as the sum of days where the subject was in remission periods. The proportion of days in remission was calculated as the number of days in remission divided by the length of the maintenance phase in days.p-value: <0.00195% CI: [0.08, 0.14]ANOVA