Psoriasis Vulgaris
Conditions
Brief summary
There are few therapies suitable for the treatment of psoriasis on the face and skin folds. As these areas are sensitive, irritation and other adverse reactions are more common than elsewhere on the body. The purpose of the study is to compare the efficacy and safety of once daily treatment for up to 8 weeks of an ointment containing calcipotriol 25 mcg/g plus hydrocortisone 10 mg/g with calcipotriol 25 mcg/g in the ointment vehicle, hydrocortisone 10 mg/g in the ointment vehicle and the ointment vehicle alone in patients with psoriasis vulgaris on the face and on the intertriginous areas (= double-blind phase). Furthermore, the safety and efficacy will be evaluated for up to 60 weeks treatment as required of calcipotriol 25 mcg/g plus hydrocortisone 10 mg/g ointment in psoriasis vulgaris on the face and intertriginous areas (= open-label phase).
Interventions
Sponsors
LEO Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of psoriasis vulgaris involving the face * Clinical signs of psoriasis vulgaris on the trunk and/or the limbs, or earlier diagnosed with psoriasis vulgaris on the trunk and/or the limbs * An extent of psoriatic involvement of the face of at least 10 cm2 (the sum of all facial lesions) * Treatment areas (the face and the intertriginous areas) amenable to topical treatment with a maximum of 100 g of ointment per week * Disease severity graded as mild, moderate, severe or very severe according to the investigator's global assessment of disease severity of the face
Exclusion criteria
* Systemic treatments with all other therapies than biologicals, with a potential effect on psoriasis vulgaris (e.g., corticosteroids, vitamin D analogues, retinoids, immunosuppressants) within the 4-week period prior to randomisation * Systemic use of biological treatments, whether marketed or not, directed against or with a potential effect on psoriasis vulgaris (e.g., alefacept, efalizumab, etanercept, infliximab, adalimumab) within 3 months prior to randomisation * PUVA therapy or Grenz ray therapy within the 4-week period prior to randomisation * UVB therapy within the 2-week period prior to randomisation * Topical treatment of the face and the intertriginous areas within the 2-week period prior to randomisation (use of emollients is allowed on treatment areas during this 2-week period, but not during the double-blind phase of the study) * Topical treatment with very potent WHO group IV corticosteroids within the 2-week period prior to randomisation * Initiation of or expected changes in concomitant medication that may affect psoriasis vulgaris (e.g., beta blockers, anti-malaria drugs, lithium and ACE inhibitors) during the study * Current diagnosis of erythrodermic, exfoliative, guttate or pustular psoriasis * Patients with any of the following conditions present on the treatment area: viral (e.g., herpes or varicella) lesions of the skin, fungal and bacterial skin infections, parasitic infections, skin manifestations in relation to syphilis or tuberculosis, rosacea, perioral dermatitis, acne vulgaris, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, acne rosacea, ulcers and wounds * Other inflammatory skin diseases (e.g., seborrhoiec dermatitis, contact dermatitis and cutaneous mycosis) that may confound the evaluation of psorisis vulgaris on the face or on the intertriginous areas * Planned exposure to sun, UVA or UVB that may affect the psoriasis vulgaris during the study * Known or suspected severe renal insufficiency or severe hepatic disorders * Known or suspected disorders of calcium metabolism associated with hypercalcaemia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Controlled Disease According to the Investigator's Global Assessment(IGA) of Disease Severity of the Face at Week 8 (Visit 6) in the Double-blind Phase | At Week 8 (end of treatment for double-blind phase) | The (sub) investigator made an assessment of the disease severity of the face using the 6-category scale below. Clear, Almost clear, Mild, Moderate, Severe, Very severe The assessment was made considering the condition of psoriasis vulgaris of the face at the time of the evaluation, not in relation to the condition at a previous visit. For subjects with a baseline (Visit 1) severity of moderate or worse - controlled disease of the face was defined as clear or almost clear according to the IGA of disease severity of the face. For subjects with a baseline (Visit 1) severity of mild - controlled disease of the face was defined as clear according to the IGA of disease severity of the face. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Controlled Disease According to the IGA of Disease Severity of the Face at Week 4 (Visit 4) in the Double-blind Phase | At Week 4 | The assessment of the disease severity of the face was made using the 6-category scale below. Clear Almost clear Mild Moderate Severe Very severe The assessment was made considering the condition of psoriasis vulgaris of the face at the time of the evaluation, not in relation to the condition at a previous visit. For subjects with a baseline severity of moderate or worse - controlled disease of the face was defined as clear or almost clear according to the IGA of disease severity of the face. For subjects with a baseline severity of mild - controlled disease of the face was defined as clear according to the IGA of disease severity of the face. |
| Participants With Success According to Total Sign Score (TSS) of the Face at Week 8 (Visit 6) in the Double-blind Phase | At Week 8 (end of treatment for double-blind phase) | Success was defined as a TSS score of 0 or 1. For each clinical sign, a single score, reflecting the average severity of all psoriatic lesions on the face was determined according to the scale below: Redness 0 = none (no erythema) 1 = mild (faint erythema, pink to very light red) 2 = moderate (definite light red erythema) 3 = severe (dark red erythema) 4 = very severe (very dark red erythema) Thickness 0 = none (no plaque elevation) 1 = mild (slight, barely perceptible elevation) 2 = moderate (definite elevation but not thick) 3 = severe (definite elevation, thick plaque with sharp edge) 4 = very severe (very thick plaque with sharp edge) Scaliness 0 = none (no scaling) 1 = mild (sparse, fine-scale lesions, only partially covered) 2 = moderate (coarser scales, most of lesions covered) 3 = severe (entire lesion covered with coarse scales) 4 = very severe (very thick coarse scales, possibly fissured) The sum of the three scores constituted a TSS ranging from 0 to 12 |
| Participants With Controlled Disease According to the IGA of Disease Severity of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase | At Week 8 (end of treatment for double-blind phase) | The (sub)investigator made an assessment of the disease severity of the intertriginous areas using the 6-category scale below. Clear, Almost clear, Mild, Moderate, Severe, Very severe The assessment was made considering the condition of psoriasis vulgaris of the intertrigi-nous areas at the time of the evaluation, not in relation to the condition at a previous visit. For subjects with a baseline severity of moderate or worse - controlled disease of the intertriginous areas was defined as clear or almost clear according to the IGA of disease severity of the intertriginous areas. For subjects with a baseline severity of mild - controlled disease of the intertriginous areas was defined as clear according to the IGA of disease severity of the intertriginous areas. |
| Participants With Success According to Total Sign Score of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase | At Week 8 (end of treatment for double-blind phase) | The severity of the subject's psoriasis vulgaris on the intertriginous areas was evaluated in terms of the three clinical signs: redness, thickness and scaliness. All the defined intertriginous areas were rated separately using the same scale as for the investigator's assessment of clinical signs (redness, thickness and scaliness) of the face. For each clinical sign, a single score, reflecting the average severity of all psoriatic lesions on the face was determined according to the scale below: Redness 0 = none 1. = mild 2. = moderate 3. = severe 4. = very severe Thickness 0 = none 1. = mild 2. = moderate 3. = severe 4. = very severe Scaliness 0 = none 1. = mild 2. = moderate 3. = severe 4. = very severe A mean score was calculated for each sign (redness, thickness and scaliness) based on scores of all the defined intertriginous areas with psoriasis at baseline and the sum of these mean scores constituted the TSS. Success was defined as a TSS score of 0 or 1. |
Countries
Croatia, Germany, Poland, Serbia
Participant flow
Recruitment details
A total of 1245 subjects were enrolled (informed consent signed and CRF started). Five subjects left the study during washout (2 screening failures, 2 lost to follow-up and 1 unacceptable adverse event). One subject attended Visit 1 but was not randomized (voluntary withdrawal). Therefore, 1239 of the enrolled subjects were randomized in the study.
Pre-assignment details
The Randomized double-blind phase of the study lasted up to 8 weeks, and was followed by a 52-week Open-label period in which participants had the opportunity to receive Calcipotriol 25 mcg/g plus 10 mg/g Hydrocortisone ointment.
Participants by arm
| Arm | Count |
|---|---|
| LEO 80190 Once daily application Calcipotriol 25 mcg/g plus 10 mg/g hydrocortisone ointment (LEO 80190) | 353 |
| Calcipotriol Once daily application Calcipotriol 25 mcg/g in the ointment vehicle | 342 |
| Hydrocortisone Once daily application Hydrocortisone 10 mg/g in the ointment vehicle | 363 |
| LEO 80190 Vehicle Once daily application Ointment Vehicle | 181 |
| Total | 1,239 |
Baseline characteristics
| Characteristic | Hydrocortisone | LEO 80190 | Calcipotriol | LEO 80190 Vehicle | Total |
|---|---|---|---|---|---|
| Age, Continuous | 43.0 years STANDARD_DEVIATION 14.1 | 42.8 years STANDARD_DEVIATION 15.3 | 44.8 years STANDARD_DEVIATION 15.1 | 44.6 years STANDARD_DEVIATION 15.1 | 43.6 years STANDARD_DEVIATION 14.9 |
| Region of Enrollment Belgium | 5 participants | 4 participants | 6 participants | 2 participants | 17 participants |
| Region of Enrollment Croatia | 16 participants | 15 participants | 13 participants | 7 participants | 51 participants |
| Region of Enrollment Czechia | 24 participants | 29 participants | 22 participants | 15 participants | 90 participants |
| Region of Enrollment Germany | 96 participants | 99 participants | 95 participants | 55 participants | 345 participants |
| Region of Enrollment Hungary | 64 participants | 58 participants | 59 participants | 35 participants | 216 participants |
| Region of Enrollment Latvia | 24 participants | 23 participants | 20 participants | 10 participants | 77 participants |
| Region of Enrollment Macedonia | 8 participants | 7 participants | 8 participants | 3 participants | 26 participants |
| Region of Enrollment Netherlands | 5 participants | 4 participants | 6 participants | 1 participants | 16 participants |
| Region of Enrollment Poland | 80 participants | 79 participants | 76 participants | 37 participants | 272 participants |
| Region of Enrollment Serbia | 40 participants | 34 participants | 36 participants | 16 participants | 126 participants |
| Region of Enrollment Slovenia | 1 participants | 1 participants | 1 participants | 0 participants | 3 participants |
| Sex: Female, Male Female | 147 Participants | 155 Participants | 139 Participants | 76 Participants | 517 Participants |
| Sex: Female, Male Male | 216 Participants | 198 Participants | 203 Participants | 105 Participants | 722 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 351 | 0 / 341 | 0 / 362 | 0 / 181 | 0 / 453 |
| other Total, other adverse events | 91 / 351 | 100 / 341 | 70 / 362 | 47 / 181 | 266 / 453 |
| serious Total, serious adverse events | 5 / 351 | 5 / 341 | 4 / 362 | 0 / 181 | 24 / 453 |
Outcome results
Primary
Participants With Controlled Disease According to the Investigator's Global Assessment(IGA) of Disease Severity of the Face at Week 8 (Visit 6) in the Double-blind Phase
The (sub) investigator made an assessment of the disease severity of the face using the 6-category scale below. Clear, Almost clear, Mild, Moderate, Severe, Very severe The assessment was made considering the condition of psoriasis vulgaris of the face at the time of the evaluation, not in relation to the condition at a previous visit. For subjects with a baseline (Visit 1) severity of moderate or worse - controlled disease of the face was defined as clear or almost clear according to the IGA of disease severity of the face. For subjects with a baseline (Visit 1) severity of mild - controlled disease of the face was defined as clear according to the IGA of disease severity of the face.
Time frame: At Week 8 (end of treatment for double-blind phase)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LEO 80190 | Participants With Controlled Disease According to the Investigator's Global Assessment(IGA) of Disease Severity of the Face at Week 8 (Visit 6) in the Double-blind Phase | 158 Participants |
| Calcipotriol | Participants With Controlled Disease According to the Investigator's Global Assessment(IGA) of Disease Severity of the Face at Week 8 (Visit 6) in the Double-blind Phase | 135 Participants |
| Hydrocortisone | Participants With Controlled Disease According to the Investigator's Global Assessment(IGA) of Disease Severity of the Face at Week 8 (Visit 6) in the Double-blind Phase | 115 Participants |
| LEO 80190 Vehicle | Participants With Controlled Disease According to the Investigator's Global Assessment(IGA) of Disease Severity of the Face at Week 8 (Visit 6) in the Double-blind Phase | 41 Participants |
Comparison: Test for superiority of LEO 80190 ointment versus calcipotriol ointment at Week 8 LOCF (Last Observation Carried Forward).p-value: 0.1195% CI: [0.94, 1.74]Cochran-Mantel-Haenszel
Comparison: Test for superiority of LEO 80190 ointment versus hydrocortisone ointment at Week 8 LOCF (Last Observation Carried Forward).p-value: <0.00195% CI: [1.31, 2.45]Cochran-Mantel-Haenszel
Comparison: Test for superiority of LEO 80190 ointment versus ointment vehicle at Week 8 LOCF (Last Observation Carried Forward).p-value: <0.00195% CI: [1.8, 4.04]Cochran-Mantel-Haenszel
Secondary
Participants With Controlled Disease According to the IGA of Disease Severity of the Face at Week 4 (Visit 4) in the Double-blind Phase
The assessment of the disease severity of the face was made using the 6-category scale below. Clear Almost clear Mild Moderate Severe Very severe The assessment was made considering the condition of psoriasis vulgaris of the face at the time of the evaluation, not in relation to the condition at a previous visit. For subjects with a baseline severity of moderate or worse - controlled disease of the face was defined as clear or almost clear according to the IGA of disease severity of the face. For subjects with a baseline severity of mild - controlled disease of the face was defined as clear according to the IGA of disease severity of the face.
Time frame: At Week 4
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LEO 80190 | Participants With Controlled Disease According to the IGA of Disease Severity of the Face at Week 4 (Visit 4) in the Double-blind Phase | 101 Participants |
| Calcipotriol | Participants With Controlled Disease According to the IGA of Disease Severity of the Face at Week 4 (Visit 4) in the Double-blind Phase | 66 Participants |
| Hydrocortisone | Participants With Controlled Disease According to the IGA of Disease Severity of the Face at Week 4 (Visit 4) in the Double-blind Phase | 61 Participants |
| LEO 80190 Vehicle | Participants With Controlled Disease According to the IGA of Disease Severity of the Face at Week 4 (Visit 4) in the Double-blind Phase | 14 Participants |
Secondary
Participants With Controlled Disease According to the IGA of Disease Severity of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase
The (sub)investigator made an assessment of the disease severity of the intertriginous areas using the 6-category scale below. Clear, Almost clear, Mild, Moderate, Severe, Very severe The assessment was made considering the condition of psoriasis vulgaris of the intertrigi-nous areas at the time of the evaluation, not in relation to the condition at a previous visit. For subjects with a baseline severity of moderate or worse - controlled disease of the intertriginous areas was defined as clear or almost clear according to the IGA of disease severity of the intertriginous areas. For subjects with a baseline severity of mild - controlled disease of the intertriginous areas was defined as clear according to the IGA of disease severity of the intertriginous areas.
Time frame: At Week 8 (end of treatment for double-blind phase)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LEO 80190 | Participants With Controlled Disease According to the IGA of Disease Severity of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase | 80 Participants |
| Calcipotriol | Participants With Controlled Disease According to the IGA of Disease Severity of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase | 55 Participants |
| Hydrocortisone | Participants With Controlled Disease According to the IGA of Disease Severity of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase | 48 Participants |
| LEO 80190 Vehicle | Participants With Controlled Disease According to the IGA of Disease Severity of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase | 14 Participants |
Secondary
Participants With Success According to Total Sign Score of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase
The severity of the subject's psoriasis vulgaris on the intertriginous areas was evaluated in terms of the three clinical signs: redness, thickness and scaliness. All the defined intertriginous areas were rated separately using the same scale as for the investigator's assessment of clinical signs (redness, thickness and scaliness) of the face. For each clinical sign, a single score, reflecting the average severity of all psoriatic lesions on the face was determined according to the scale below: Redness 0 = none 1. = mild 2. = moderate 3. = severe 4. = very severe Thickness 0 = none 1. = mild 2. = moderate 3. = severe 4. = very severe Scaliness 0 = none 1. = mild 2. = moderate 3. = severe 4. = very severe A mean score was calculated for each sign (redness, thickness and scaliness) based on scores of all the defined intertriginous areas with psoriasis at baseline and the sum of these mean scores constituted the TSS. Success was defined as a TSS score of 0 or 1.
Time frame: At Week 8 (end of treatment for double-blind phase)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LEO 80190 | Participants With Success According to Total Sign Score of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase | 82 Participants |
| Calcipotriol | Participants With Success According to Total Sign Score of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase | 81 Participants |
| Hydrocortisone | Participants With Success According to Total Sign Score of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase | 59 Participants |
| LEO 80190 Vehicle | Participants With Success According to Total Sign Score of the Intertriginous Areas at Week 8 (Visit 6) in the Double-blind Phase | 15 Participants |
Secondary
Participants With Success According to Total Sign Score (TSS) of the Face at Week 8 (Visit 6) in the Double-blind Phase
Success was defined as a TSS score of 0 or 1. For each clinical sign, a single score, reflecting the average severity of all psoriatic lesions on the face was determined according to the scale below: Redness 0 = none (no erythema) 1 = mild (faint erythema, pink to very light red) 2 = moderate (definite light red erythema) 3 = severe (dark red erythema) 4 = very severe (very dark red erythema) Thickness 0 = none (no plaque elevation) 1 = mild (slight, barely perceptible elevation) 2 = moderate (definite elevation but not thick) 3 = severe (definite elevation, thick plaque with sharp edge) 4 = very severe (very thick plaque with sharp edge) Scaliness 0 = none (no scaling) 1 = mild (sparse, fine-scale lesions, only partially covered) 2 = moderate (coarser scales, most of lesions covered) 3 = severe (entire lesion covered with coarse scales) 4 = very severe (very thick coarse scales, possibly fissured) The sum of the three scores constituted a TSS ranging from 0 to 12
Time frame: At Week 8 (end of treatment for double-blind phase)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LEO 80190 | Participants With Success According to Total Sign Score (TSS) of the Face at Week 8 (Visit 6) in the Double-blind Phase | 171 Participants |
| Calcipotriol | Participants With Success According to Total Sign Score (TSS) of the Face at Week 8 (Visit 6) in the Double-blind Phase | 136 Participants |
| Hydrocortisone | Participants With Success According to Total Sign Score (TSS) of the Face at Week 8 (Visit 6) in the Double-blind Phase | 131 Participants |
| LEO 80190 Vehicle | Participants With Success According to Total Sign Score (TSS) of the Face at Week 8 (Visit 6) in the Double-blind Phase | 42 Participants |