Psoriasis Vulgaris
Conditions
Brief summary
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.
Interventions
DRUGLEO 19123 Cream (calcipotriol plus LEO 80122)
Once daily application
DRUGDovonex® cream
Twice daily application
DRUGCream vehicle
Twice 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 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage Change in PASI (Psoriasis Area Severity Index) | From baseline (Day 0) to end of treatment (Day 28) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Controlled Disease According to the Investigator's Global Assessment of Disease Severity | At end of treatment (Day 28) | 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. |
| Participant's Overall Assessment of Treatment Response | At end of treatment (Day 28) | 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 |
| Participant's Assessment of Treatment Preference | At end of treatment (Day 28) | — |
| Investigator's Global Assessment of Disease Severity | At end of treatment (Day 28) | 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 |
| 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) | From baseline to end of treatment (Day 28) | 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. |
| Participants With at Least 75% Reduction in PASI (PASI 75) | From baseline (Day 0) to end of treatment (Day 28) | — |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A * LEO 19123 (calcipotriol 50 mcg/g plus LEO 80122 0.6 mg/g) cream for topical application once daily in the evening to lesions on one side of the body. Maximum 50 g/week
* Dovonex® (calcipotriol 50 mcg/g) cream for topical application twice daily to the lesions on the other side of the body. Maximum 50 g/week. | 39 |
| Group B * LEO 19123 (calcipotriol 50 mcg/g plus LEO 80122 0.6 mg/g) cream for topical application once daily in the evening to lesions on one side of the body. Maximum 50 g/week.
* LEO 19123 cream vehicle for topical application twice daily to the lesions on the other side of the body. Maximum 50 g/week. | 12 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Psoriasis flare up on the scalp | 1 | 0 |
Baseline characteristics
| Characteristic | Group A | Group B | Total |
|---|---|---|---|
| Age, Continuous | 53.7 years STANDARD_DEVIATION 14.3 | 57.7 years STANDARD_DEVIATION 9.8 | 54.7 years STANDARD_DEVIATION 13.4 |
| Region of Enrollment Canada | 39 participants | 12 participants | 51 participants |
| Sex: Female, Male Female | 11 Participants | 3 Participants | 14 Participants |
| Sex: Female, Male Male | 28 Participants | 9 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 38 | 6 / 12 |
| serious Total, serious adverse events | 1 / 38 | 0 / 12 |
Outcome results
Primary
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.
Time frame: From baseline (Day 0) to end of treatment (Day 28)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: LEO 19123 | The Percentage Change in PASI (Psoriasis Area Severity Index) | -24.8 percentage change in PASI | Standard Deviation 33.2 |
| Group A: Dovonex® | The Percentage Change in PASI (Psoriasis Area Severity Index) | -40.2 percentage change in PASI | Standard Deviation 27.8 |
| Group B: LEO 19123 | The Percentage Change in PASI (Psoriasis Area Severity Index) | -46.8 percentage change in PASI | Standard Deviation 27 |
| Group B: LEO 19123 Vehicle | The Percentage Change in PASI (Psoriasis Area Severity Index) | -29.8 percentage change in PASI | Standard Deviation 20.9 |
p-value: =0.00395% CI: [5.6, 25]Paired t-test
p-value: 0.0795% CI: [-36, 1.9]Paired t-test
Secondary
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
Time frame: At end of treatment (Day 28)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: LEO 19123 | Investigator's Global Assessment of Disease Severity | Clear | 0 Participants |
| Group A: LEO 19123 | Investigator's Global Assessment of Disease Severity | Almost clear | 3 Participants |
| Group A: LEO 19123 | Investigator's Global Assessment of Disease Severity | Mild | 8 Participants |
| Group A: LEO 19123 | Investigator's Global Assessment of Disease Severity | Moderate | 24 Participants |
| Group A: LEO 19123 | Investigator's Global Assessment of Disease Severity | Severe | 4 Participants |
| Group A: LEO 19123 | Investigator's Global Assessment of Disease Severity | Very severe | 0 Participants |
| Group A: Dovonex® | Investigator's Global Assessment of Disease Severity | Very severe | 0 Participants |
| Group A: Dovonex® | Investigator's Global Assessment of Disease Severity | Moderate | 20 Participants |
| Group A: Dovonex® | Investigator's Global Assessment of Disease Severity | Clear | 0 Participants |
| Group A: Dovonex® | Investigator's Global Assessment of Disease Severity | Mild | 17 Participants |
| Group A: Dovonex® | Investigator's Global Assessment of Disease Severity | Almost clear | 1 Participants |
| Group A: Dovonex® | Investigator's Global Assessment of Disease Severity | Severe | 1 Participants |
| Group B: LEO 19123 | Investigator's Global Assessment of Disease Severity | Almost clear | 4 Participants |
| Group B: LEO 19123 | Investigator's Global Assessment of Disease Severity | Mild | 3 Participants |
| Group B: LEO 19123 | Investigator's Global Assessment of Disease Severity | Moderate | 5 Participants |
| Group B: LEO 19123 | Investigator's Global Assessment of Disease Severity | Very severe | 0 Participants |
| Group B: LEO 19123 | Investigator's Global Assessment of Disease Severity | Severe | 0 Participants |
| Group B: LEO 19123 | Investigator's Global Assessment of Disease Severity | Clear | 0 Participants |
| Group B: LEO 19123 Vehicle | Investigator's Global Assessment of Disease Severity | Severe | 2 Participants |
| Group B: LEO 19123 Vehicle | Investigator's Global Assessment of Disease Severity | Very severe | 0 Participants |
| Group B: LEO 19123 Vehicle | Investigator's Global Assessment of Disease Severity | Almost clear | 0 Participants |
| Group B: LEO 19123 Vehicle | Investigator's Global Assessment of Disease Severity | Moderate | 5 Participants |
| Group B: LEO 19123 Vehicle | Investigator's Global Assessment of Disease Severity | Clear | 0 Participants |
| Group B: LEO 19123 Vehicle | Investigator's Global Assessment of Disease Severity | Mild | 5 Participants |
Secondary
Participant's Assessment of Treatment Preference
Time frame: At end of treatment (Day 28)
Population: All randomized participants have been included in the analysis. One participant withdrew and did therefore not give their preference.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: LEO 19123 | Participant's Assessment of Treatment Preference | LEO 19123 | 5 Participants |
| Group A: LEO 19123 | Participant's Assessment of Treatment Preference | No preference | 12 Participants |
| Group A: LEO 19123 | Participant's Assessment of Treatment Preference | Reference product | 21 Participants |
| Group A: Dovonex® | Participant's Assessment of Treatment Preference | LEO 19123 | 6 Participants |
| Group A: Dovonex® | Participant's Assessment of Treatment Preference | No preference | 3 Participants |
| Group A: Dovonex® | Participant's Assessment of Treatment Preference | Reference product | 3 Participants |
Secondary
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
Time frame: At end of treatment (Day 28)
Population: All randomized participants have been included in the analysis. One participant withdrew and did therefore not give their assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: LEO 19123 | Participant's Overall Assessment of Treatment Response | Worse | 2 Participants |
| Group A: LEO 19123 | Participant's Overall Assessment of Treatment Response | Almost clear | 0 Participants |
| Group A: LEO 19123 | Participant's Overall Assessment of Treatment Response | Marked improvement | 3 Participants |
| Group A: LEO 19123 | Participant's Overall Assessment of Treatment Response | Unchanged | 9 Participants |
| Group A: LEO 19123 | Participant's Overall Assessment of Treatment Response | Clear | 0 Participants |
| Group A: LEO 19123 | Participant's Overall Assessment of Treatment Response | Slight improvement | 12 Participants |
| Group A: LEO 19123 | Participant's Overall Assessment of Treatment Response | Moderate improvement | 12 Participants |
| Group A: Dovonex® | Participant's Overall Assessment of Treatment Response | Almost clear | 0 Participants |
| Group A: Dovonex® | Participant's Overall Assessment of Treatment Response | Moderate improvement | 12 Participants |
| Group A: Dovonex® | Participant's Overall Assessment of Treatment Response | Slight improvement | 9 Participants |
| Group A: Dovonex® | Participant's Overall Assessment of Treatment Response | Marked improvement | 12 Participants |
| Group A: Dovonex® | Participant's Overall Assessment of Treatment Response | Clear | 0 Participants |
| Group A: Dovonex® | Participant's Overall Assessment of Treatment Response | Unchanged | 4 Participants |
| Group A: Dovonex® | Participant's Overall Assessment of Treatment Response | Worse | 1 Participants |
| Group B: LEO 19123 | Participant's Overall Assessment of Treatment Response | Moderate improvement | 5 Participants |
| Group B: LEO 19123 | Participant's Overall Assessment of Treatment Response | Worse | 1 Participants |
| Group B: LEO 19123 | Participant's Overall Assessment of Treatment Response | Unchanged | 3 Participants |
| Group B: LEO 19123 | Participant's Overall Assessment of Treatment Response | Slight improvement | 1 Participants |
| Group B: LEO 19123 | Participant's Overall Assessment of Treatment Response | Marked improvement | 2 Participants |
| Group B: LEO 19123 | Participant's Overall Assessment of Treatment Response | Almost clear | 0 Participants |
| Group B: LEO 19123 | Participant's Overall Assessment of Treatment Response | Clear | 0 Participants |
| Group B: LEO 19123 Vehicle | Participant's Overall Assessment of Treatment Response | Slight improvement | 7 Participants |
| Group B: LEO 19123 Vehicle | Participant's Overall Assessment of Treatment Response | Clear | 0 Participants |
| Group B: LEO 19123 Vehicle | Participant's Overall Assessment of Treatment Response | Almost clear | 0 Participants |
| Group B: LEO 19123 Vehicle | Participant's Overall Assessment of Treatment Response | Unchanged | 3 Participants |
| Group B: LEO 19123 Vehicle | Participant's Overall Assessment of Treatment Response | Worse | 0 Participants |
| Group B: LEO 19123 Vehicle | Participant's Overall Assessment of Treatment Response | Marked improvement | 1 Participants |
| Group B: LEO 19123 Vehicle | Participant's Overall Assessment of Treatment Response | Moderate improvement | 1 Participants |
Secondary
Participants With at Least 50% Reduction in PASI (PASI 50)
Time frame: From baseline (Day 0) to end of treatment (day 28)
Population: All randomised participants have been included in the analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: LEO 19123 | Participants With at Least 50% Reduction in PASI (PASI 50) | >= 50% PASI reduction | 9 Participants |
| Group A: LEO 19123 | Participants With at Least 50% Reduction in PASI (PASI 50) | < 50% PASI reduction | 30 Participants |
| Group A: Dovonex® | Participants With at Least 50% Reduction in PASI (PASI 50) | < 50% PASI reduction | 24 Participants |
| Group A: Dovonex® | Participants With at Least 50% Reduction in PASI (PASI 50) | >= 50% PASI reduction | 15 Participants |
| Group B: LEO 19123 | Participants With at Least 50% Reduction in PASI (PASI 50) | >= 50% PASI reduction | 7 Participants |
| Group B: LEO 19123 | Participants With at Least 50% Reduction in PASI (PASI 50) | < 50% PASI reduction | 5 Participants |
| Group B: LEO 19123 Vehicle | Participants With at Least 50% Reduction in PASI (PASI 50) | >= 50% PASI reduction | 2 Participants |
| Group B: LEO 19123 Vehicle | Participants With at Least 50% Reduction in PASI (PASI 50) | < 50% PASI reduction | 10 Participants |
Secondary
Participants With at Least 75% Reduction in PASI (PASI 75)
Time frame: From baseline (Day 0) to end of treatment (Day 28)
Population: Two participants withdrew from the LEO 19123 versus Dovonex® group at Week 2.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: LEO 19123 | Participants With at Least 75% Reduction in PASI (PASI 75) | >=75% PASI reduction | 2 Participants |
| Group A: LEO 19123 | Participants With at Least 75% Reduction in PASI (PASI 75) | 75% PASI reduction | 37 Participants |
| Group A: Dovonex® | Participants With at Least 75% Reduction in PASI (PASI 75) | 75% PASI reduction | 35 Participants |
| Group A: Dovonex® | Participants With at Least 75% Reduction in PASI (PASI 75) | >=75% PASI reduction | 4 Participants |
| Group B: LEO 19123 | Participants With at Least 75% Reduction in PASI (PASI 75) | >=75% PASI reduction | 1 Participants |
| Group B: LEO 19123 | Participants With at Least 75% Reduction in PASI (PASI 75) | 75% PASI reduction | 11 Participants |
| Group B: LEO 19123 Vehicle | Participants With at Least 75% Reduction in PASI (PASI 75) | >=75% PASI reduction | 0 Participants |
| Group B: LEO 19123 Vehicle | Participants With at Least 75% Reduction in PASI (PASI 75) | 75% PASI reduction | 12 Participants |
Secondary
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.
Time frame: At end of treatment (Day 28)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: LEO 19123 | Participants With Controlled Disease According to the Investigator's Global Assessment of Disease Severity | Controlled disease | 2 Participants |
| Group A: LEO 19123 | Participants With Controlled Disease According to the Investigator's Global Assessment of Disease Severity | No controlled disease | 37 Participants |
| Group A: Dovonex® | Participants With Controlled Disease According to the Investigator's Global Assessment of Disease Severity | No controlled disease | 38 Participants |
| Group A: Dovonex® | Participants With Controlled Disease According to the Investigator's Global Assessment of Disease Severity | Controlled disease | 1 Participants |
| Group B: LEO 19123 | Participants With Controlled Disease According to the Investigator's Global Assessment of Disease Severity | Controlled disease | 4 Participants |
| Group B: LEO 19123 | Participants With Controlled Disease According to the Investigator's Global Assessment of Disease Severity | No controlled disease | 8 Participants |
| Group B: LEO 19123 Vehicle | Participants With Controlled Disease According to the Investigator's Global Assessment of Disease Severity | Controlled disease | 0 Participants |
| Group B: LEO 19123 Vehicle | Participants With Controlled Disease According to the Investigator's Global Assessment of Disease Severity | No controlled disease | 12 Participants |
Secondary
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.
Time frame: From baseline to end of treatment (Day 28)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: LEO 19123 | The Absolute Change in PASI (Psoriasis Area Severity Index) | -2.6 units on a scale | Standard Deviation 4 |
| Group A: Dovonex® | The Absolute Change in PASI (Psoriasis Area Severity Index) | -3.8 units on a scale | Standard Deviation 3.6 |
| Group B: LEO 19123 | The Absolute Change in PASI (Psoriasis Area Severity Index) | -4.2 units on a scale | Standard Deviation 2.9 |
| Group B: LEO 19123 Vehicle | The Absolute Change in PASI (Psoriasis Area Severity Index) | -2.5 units on a scale | Standard Deviation 2.1 |