Psoriasis Vulgaris
Conditions
Brief summary
This study will compare efficacy and safety of once daily treatment of calcipotriol plus betamethasone dipropionate gel (LEO 80185) with tacalcitol ointment and LEO 80185 vehicle alone in subjects with psoriasis vulgaris. Subjects will be treated for up to 8 weeks followed by an observation period of up to 8 weeks to investigate the occurence and the time to relapse and occurence of rebound after discontinuation of the investigational products. Only subjects with controlled disease will be considered for this observation phase of the study. Controlled disease is defined as Clear or Almost Clear severity category based on Investigator's global assessment (IGA).
Interventions
DRUGcalcipotriol and betamethasone (LEO 80185 gel)
Once daily application
DRUGLEO 80185 vehicle
Once daily application
Once daily application
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
* Signed and dated informed consent to be obtained prior to any trial related procedure, including wash-out * Clinical diagnosis of psoriasis vulgaris involving trunk and/or arms and/or legs amenable to treatment with a maximum of 100 g of LEO 80185 gel per week or 10 g per day of tacalcitol ointment * Disease severity graded moderate, severe or very severe according to the Investigator's global assessment (IGA) of disease severity * A minimum PASI score for extent of 2 in at least one body region (i.e.psoriasis affecting at least 10% of arms, and/or 10% of trunk, and/or 10% of legs) * Subjects aged 18 years or above * Either sex * Any ethnic origin * Attending hospital outpatient clinic or the private practice of a dermatologist
Exclusion criteria
* Systemic treatment with biological therapies (marketed or not marketed), with a possible effect on psoriasis vulgaris (e.g., alefacept, efalizumab, etanercept, infliximab, adalimumab) within 3 months prior to randomisation * Systemic treatment with all other therapies than biologics, with a possible effect on psoriasis vulgaris (e.g., corticosteroids, retinoids, immunosuppressants) within 4 weeks prior to randomisation * Systemic treatment with Vitamin D preparations above 500 IU per day * PUVA or Grenz ray therapy within 4 weeks prior to randomization * UVB therapy within 2 weeks prior to randomisation * Any topical treatment of the trunk/limbs (except for emollients) 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 or vitamin D analogues 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 or vitamin D analogues 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) during the study * Current diagnosis of erythrodermic, exfoliative or pustular psoriasis * Subjects with any of the following conditions present on the treatment area: viral (e.g., herpes or varicella) lesions, fungal and bacterial skin infections, parasitic infections, skin manifestations in relation to syphilis or tuberculosis, rosacea, perioral dermatitis, acne vulgaris, atrophic skin, striae atro-phicae, fragility of skin veins, ichthyosis, acne rosacea, ulcers and wounds * Known or suspected disorders of calcium metabolism associated with hypercalcaemia * Known or suspected severe renal insufficiency or severe hepatic disorders * Known or suspected hypersensitivity to component(s) of the Investigational Products * Current participation in any other interventional clinical study * 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, except for biologics (3 months) * Planned exposure to sun during the study that may affect psoriasis vulgaris * Previously randomised to this study * Subjects known or suspected of not being able to comply with a trial protocol (e.g. due to alcoholism, drug dependency or psychotic state) * Females of child-bearing potential wishing to become pregnant during the study, or are breast-feeding, or not using an adequate method of contraception during the study * Females of child-bearing potential with positive pregnancy test at Visit 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Subjects With Controlled Disease (Clear or Almost Clear Disease) According to Investigator's Global Assessment of Disease Severity at Week 8 | Week 8 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjects With Controlled Disease According to the Investigator's Global Assessment of Disease Severity at Week 4 | Week 4 | — |
| The Percentage Change in PASI From Baseline to Week 8 | Baseline, Week 4 and 8 | PASI is Psoriasis Area and Severity Index and is based on the investigator's assessment of extent and severity of the disease. It can range from 0 (best) to 64.8 (worst). |
| Subjects With Relapse During the Study | Week 8-16 | Among subjects with controlled disease at week 8 relapse was defined as PASI exceeding the baseline PASI value minus 50% of the reduction in PASI obtained from the baseline visit to the last on-treatment visit |
| Subjects With Rebound During the Study | Week 8-16 | — |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Calcipotriol Plus Betamethasone Dipropionate Gel Calcipotriol Plus Betamethasone Dipropionate Gel for up to 8 weeks | 183 |
| Tacalcitol Ointment Tacalcitol Ointment for up to 8 weeks | 184 |
| Gel Vehicle Gel Vehicle for up to 8 weeks | 91 |
| Total | 458 |
Baseline characteristics
| Characteristic | Tacalcitol Ointment | Gel Vehicle | Calcipotriol Plus Betamethasone Dipropionate Gel | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 29 Participants | 17 Participants | 35 Participants | 81 Participants |
| Age, Categorical Between 18 and 65 years | 155 Participants | 74 Participants | 148 Participants | 377 Participants |
| Age, Continuous | 51.7 years STANDARD_DEVIATION 13.4 | 52.8 years STANDARD_DEVIATION 14.9 | 50.9 years STANDARD_DEVIATION 14.3 | 51.6 years STANDARD_DEVIATION 14 |
| Region of Enrollment Canada | 184 participants | 91 participants | 183 participants | 458 participants |
| Sex: Female, Male Female | 69 Participants | 38 Participants | 66 Participants | 173 Participants |
| Sex: Female, Male Male | 115 Participants | 53 Participants | 117 Participants | 285 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 25 / 182 | 28 / 184 | 10 / 91 |
| serious Total, serious adverse events | 0 / 182 | 4 / 184 | 1 / 91 |
Outcome results
Primary
Subjects With Controlled Disease (Clear or Almost Clear Disease) According to Investigator's Global Assessment of Disease Severity at Week 8
Time frame: Week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Calcipotriol Plus Betamethasone Dipropionate Gel | Subjects With Controlled Disease (Clear or Almost Clear Disease) According to Investigator's Global Assessment of Disease Severity at Week 8 | 73 Participants |
| Tacalcitol Ointment | Subjects With Controlled Disease (Clear or Almost Clear Disease) According to Investigator's Global Assessment of Disease Severity at Week 8 | 33 Participants |
| Gel Vehicle | Subjects With Controlled Disease (Clear or Almost Clear Disease) According to Investigator's Global Assessment of Disease Severity at Week 8 | 5 Participants |
p-value: <0.00195% CI: [2.05, 5.7]Cochran-Mantel-Haenszel
Secondary
Subjects With Controlled Disease According to the Investigator's Global Assessment of Disease Severity at Week 4
Time frame: Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Calcipotriol Plus Betamethasone Dipropionate Gel | Subjects With Controlled Disease According to the Investigator's Global Assessment of Disease Severity at Week 4 | 34 participants |
| Tacalcitol Ointment | Subjects With Controlled Disease According to the Investigator's Global Assessment of Disease Severity at Week 4 | 12 participants |
| Gel Vehicle | Subjects With Controlled Disease According to the Investigator's Global Assessment of Disease Severity at Week 4 | 1 participants |
p-value: <0.00198.33% CI: [1.46, 8.4]Cochran-Mantel-Haenszel
Secondary
Subjects With Rebound During the Study
Time frame: Week 8-16
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Calcipotriol Plus Betamethasone Dipropionate Gel | Subjects With Rebound During the Study | 0 participants |
| Tacalcitol Ointment | Subjects With Rebound During the Study | 0 participants |
| Gel Vehicle | Subjects With Rebound During the Study | 0 participants |
Secondary
Subjects With Relapse During the Study
Among subjects with controlled disease at week 8 relapse was defined as PASI exceeding the baseline PASI value minus 50% of the reduction in PASI obtained from the baseline visit to the last on-treatment visit
Time frame: Week 8-16
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Calcipotriol Plus Betamethasone Dipropionate Gel | Subjects With Relapse During the Study | 28 participants |
| Tacalcitol Ointment | Subjects With Relapse During the Study | 7 participants |
| Gel Vehicle | Subjects With Relapse During the Study | 3 participants |
Secondary
The Percentage Change in PASI From Baseline to Week 8
PASI is Psoriasis Area and Severity Index and is based on the investigator's assessment of extent and severity of the disease. It can range from 0 (best) to 64.8 (worst).
Time frame: Baseline, Week 4 and 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Calcipotriol Plus Betamethasone Dipropionate Gel | The Percentage Change in PASI From Baseline to Week 8 | -57.0 Percent change in PASI score |
| Tacalcitol Ointment | The Percentage Change in PASI From Baseline to Week 8 | -41.9 Percent change in PASI score |
| Gel Vehicle | The Percentage Change in PASI From Baseline to Week 8 | -17.9 Percent change in PASI score |
p-value: <0.00198.33% CI: [-22.6, -6.9]ANOVA