Psoriasis Vulgaris
Conditions
Keywords
Psoriasis Vulgaris, Systemic, Anti-psoriatic
Brief summary
An international, multi-centre, prospective, randomised, double-blind, 4-arm, placebo controlled, parallel group study with 12 weeks once daily oral treatment in subjects with psoriasis vulgaris.
Interventions
DRUGLEO 22811
Oral solution
DRUGPlacebo
Placebo
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
* Following verbal and written information about the trial the subject must provide signed and dated informed consent before any study related activity is carried out, including activities relating to the washout period. * Clinical diagnosis of psoriasis vulgaris, for at least 6 months prior to randomisation, and currently covering at least 10% of the body surface area (BSA) * Candidates for systemic anti-psoriatic treatment * Psoriasis Area and Severity Index (PASI) ≥10 * Disease severity of moderate, severe or very severe according to the Investigators' Global Assessment of disease severity (IGA) * Aged 18 years or above * Any race or ethnicity * Males, surgically sterile females (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or post menopausal females (at least 1 year since last menses) * Attending hospital outpatient clinic or the private practice of a dermatologist
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 randomisation: * Etanercept - 4 weeks * Adalimumab, alefacept, infliximab - 2 months * Ustekinumab - 4 months * Systemic treatment with all other therapies (other than biologics) with a possible effect on psoriasis vulgaris (e.g.corticosteroids, retinoids, immunosuppressants, methotrexate, cyclosporin or fumaric acid) within 4 weeks prior to randomisation * PUVA therapy within 4 weeks prior to randomisation * UVB therapy within 2 weeks prior to randomisation * Any topical treatment (except for emollients/ medicated shampoo) within 2 weeks prior to randomisation * Initiation of, or changes to concomitant medication that could affect psoriasis vulgaris (e.g. beta-blockers, anti-malaria drugs, lithium) 2 weeks prior to randomisation and during the study * Current diagnosis with erythrodermic, exfoliative or pustular psoriasis * Other current skin conditions that may confound the evaluation of psoriasis vulgaris as judged by the Investigator * Generally in good health and does not have any clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, haematologic, or gastrointestinal disease, immunologic insufficiency, or other major diseases or current condition which, in the opinion of the Investigator, would put the subject at risk by participating in the study * Current active tuberculosis or latent tuberculosis * Planned exposure to the sun during the study that may affect psoriasis vulgaris * Known malignancy or history of malignancy (other than cervical carcinoma in situ, basal cell or squamous cell carcinoma) within the 5 year period prior to randomisation * Live vaccination within the 4 weeks prior to randomisation * Males who do not agree to use adequate contraception during the study (including follow-up) to ensure their partner does not become pregnant * Known or suspected hypersensitivity to component(s) of the investigational product * Current participation in any other interventional trial * Treatment with any non-marketed drug substance (i.e. an agent which has not yet been made available for clinical use following registration) within 4 weeks or 5 half-lives (whichever is longer) prior to randomisation * Previously randomised in this study * Known or, in the opinion of the Investigator, is unlikely to comply with the Clinical Study Protocol (e.g., alcohol abuse, drug dependency or psychotic state).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Psoriasis Area and Severity Index (PASI) | Baseline (Day 0) to end of treatment (Day 84) | The investigator made assessments of the extent and severity of clinical signs of the participant's psoriasis on specific areas of the body in terms of three clinical signs: redness, thickness and scaliness. The extent of psoriatic involvement was recorded for each of four areas; head, arms, trunk and legs using the following scale: 0\. = no involvement 1. = \<10% 2. = 10-29% 3. = 30-49% 4. = 50-69% 5. = 70-89% 6. = 90-100% For each clinical sign a single score (0, 1, 2, 3 or 4) reflecting the average severity of all psoriatic lesions on the given body region was determined. PASI was calculated based on the investigator's assessment of the disease locally (head, trunk, arm, legs) using the following formula: Head: 0.1 (R + T + S)E = W Arms: 0.2 (R + T + S)E = X Trunk: 0.3 (R + T + S)E = Y Legs: 0.4 (R + T + S)E = Z R = score for redness; T = score for thickness, S = score for scaliness; E = score for extent The sum of W+X+Y+Z gives the total PASI that ranges from 0 to 72. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With at Least 75% Reduction in PASI (PASI 75) | From baseline (Day 0) to end of treatment (Day 84) | — |
| Participants With at Least 50% Reduction in PASI (PASI 50) | From baseline (Day 0) to end of treatment (Day 84) | — |
| Participants With Controlled Disease According to the Investigators' Global Assessment (IGA) | At end of treatment (Day 84) | At Visits 1 to 8 the investigator made a global assessment of the disease severity (IGA) using a 6-point scale (clear, almost clear, mild, moderate, severe, very severe). This assessment represents average lesion severity on head, trunk, arm and legs. The assessment was based on the condition of the disease at the time of evaluation and not in relation to the condition at a previous visit. Participants classified as clear or almost clear according to IGA was considered to have controlled disease. |
| Participants With Satisfactory Response According to IGA | At end of treatment (Day 84) | Satisfactory response was defined as participants classified as Clear or Almost Clear or Mild according to the IGA. |
Countries
Canada, France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LEO 22811 0.5 mg LEO 22811 0.5 mg: Oral solution | 16 |
| LEO 22811 1.5 mg LEO 22811 1.5 mg: Oral solution | 15 |
| LEO 22811 3.0 mg LEO 22811 3.0 mg: Oral solution | 18 |
| Placebo Placebo: Oral solution | 14 |
| Total | 63 |
Baseline characteristics
| Characteristic | LEO 22811 0.5 mg | LEO 22811 1.5 mg | LEO 22811 3.0 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 47.5 years STANDARD_DEVIATION 9.3 | 49.8 years STANDARD_DEVIATION 14.1 | 42.4 years STANDARD_DEVIATION 13.6 | 44.9 years STANDARD_DEVIATION 12 | 46.0 years STANDARD_DEVIATION 12.5 |
| Region of Enrollment Canada | 7 Participants | 8 Participants | 8 Participants | 7 Participants | 30 Participants |
| Region of Enrollment France | 9 Participants | 7 Participants | 10 Participants | 7 Participants | 33 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 4 Participants | 1 Participants | 11 Participants |
| Sex: Female, Male Male | 14 Participants | 11 Participants | 14 Participants | 13 Participants | 52 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 | 0 / 14 | 0 / 16 | 0 / 15 | 0 / 18 |
| other Total, other adverse events | 10 / 14 | 11 / 16 | 11 / 15 | 15 / 18 |
| serious Total, serious adverse events | 0 / 14 | 1 / 16 | 1 / 15 | 0 / 18 |
Outcome results
Primary
Percentage Change in Psoriasis Area and Severity Index (PASI)
The investigator made assessments of the extent and severity of clinical signs of the participant's psoriasis on specific areas of the body in terms of three clinical signs: redness, thickness and scaliness. The extent of psoriatic involvement was recorded for each of four areas; head, arms, trunk and legs using the following scale: 0\. = no involvement 1. = \<10% 2. = 10-29% 3. = 30-49% 4. = 50-69% 5. = 70-89% 6. = 90-100% For each clinical sign a single score (0, 1, 2, 3 or 4) reflecting the average severity of all psoriatic lesions on the given body region was determined. PASI was calculated based on the investigator's assessment of the disease locally (head, trunk, arm, legs) using the following formula: Head: 0.1 (R + T + S)E = W Arms: 0.2 (R + T + S)E = X Trunk: 0.3 (R + T + S)E = Y Legs: 0.4 (R + T + S)E = Z R = score for redness; T = score for thickness, S = score for scaliness; E = score for extent The sum of W+X+Y+Z gives the total PASI that ranges from 0 to 72.
Time frame: Baseline (Day 0) to end of treatment (Day 84)
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change in Psoriasis Area and Severity Index (PASI) | -5.6 percentage of change in PASI index score | Standard Deviation 44.9 |
| LEO 22811 0.5 mg | Percentage Change in Psoriasis Area and Severity Index (PASI) | -7.6 percentage of change in PASI index score | Standard Deviation 29.1 |
| LEO 22811 1.5 mg | Percentage Change in Psoriasis Area and Severity Index (PASI) | -0.3 percentage of change in PASI index score | Standard Deviation 43.5 |
| LEO 22811 3.0 mg | Percentage Change in Psoriasis Area and Severity Index (PASI) | -12.7 percentage of change in PASI index score | Standard Deviation 45.2 |
p-value: 0.8995% CI: [-32.6, 28.2]ANOVA
p-value: 0.7795% CI: [-26.2, 35.3]ANOVA
p-value: 0.6595% CI: [-36.2, 22.8]ANOVA
Secondary
Participants With at Least 50% Reduction in PASI (PASI 50)
Time frame: From baseline (Day 0) to end of treatment (Day 84)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Participants With at Least 50% Reduction in PASI (PASI 50) | Yes | 2 Participants |
| Placebo | Participants With at Least 50% Reduction in PASI (PASI 50) | No | 12 Participants |
| LEO 22811 0.5 mg | Participants With at Least 50% Reduction in PASI (PASI 50) | No | 15 Participants |
| LEO 22811 0.5 mg | Participants With at Least 50% Reduction in PASI (PASI 50) | Yes | 1 Participants |
| LEO 22811 1.5 mg | Participants With at Least 50% Reduction in PASI (PASI 50) | Yes | 2 Participants |
| LEO 22811 1.5 mg | Participants With at Least 50% Reduction in PASI (PASI 50) | No | 13 Participants |
| LEO 22811 3.0 mg | Participants With at Least 50% Reduction in PASI (PASI 50) | Yes | 4 Participants |
| LEO 22811 3.0 mg | Participants With at Least 50% Reduction in PASI (PASI 50) | No | 14 Participants |
Secondary
Participants With at Least 75% Reduction in PASI (PASI 75)
Time frame: From baseline (Day 0) to end of treatment (Day 84)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Participants With at Least 75% Reduction in PASI (PASI 75) | Yes | 0 Participants |
| Placebo | Participants With at Least 75% Reduction in PASI (PASI 75) | No | 14 Participants |
| LEO 22811 0.5 mg | Participants With at Least 75% Reduction in PASI (PASI 75) | No | 15 Participants |
| LEO 22811 0.5 mg | Participants With at Least 75% Reduction in PASI (PASI 75) | Yes | 1 Participants |
| LEO 22811 1.5 mg | Participants With at Least 75% Reduction in PASI (PASI 75) | Yes | 0 Participants |
| LEO 22811 1.5 mg | Participants With at Least 75% Reduction in PASI (PASI 75) | No | 15 Participants |
| LEO 22811 3.0 mg | Participants With at Least 75% Reduction in PASI (PASI 75) | Yes | 2 Participants |
| LEO 22811 3.0 mg | Participants With at Least 75% Reduction in PASI (PASI 75) | No | 16 Participants |
Secondary
Participants With Controlled Disease According to the Investigators' Global Assessment (IGA)
At Visits 1 to 8 the investigator made a global assessment of the disease severity (IGA) using a 6-point scale (clear, almost clear, mild, moderate, severe, very severe). This assessment represents average lesion severity on head, trunk, arm and legs. The assessment was based on the condition of the disease at the time of evaluation and not in relation to the condition at a previous visit. Participants classified as clear or almost clear according to IGA was considered to have controlled disease.
Time frame: At end of treatment (Day 84)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Participants With Controlled Disease According to the Investigators' Global Assessment (IGA) | Controlled | 0 Participants |
| Placebo | Participants With Controlled Disease According to the Investigators' Global Assessment (IGA) | Non-controlled | 14 Participants |
| LEO 22811 0.5 mg | Participants With Controlled Disease According to the Investigators' Global Assessment (IGA) | Non-controlled | 16 Participants |
| LEO 22811 0.5 mg | Participants With Controlled Disease According to the Investigators' Global Assessment (IGA) | Controlled | 0 Participants |
| LEO 22811 1.5 mg | Participants With Controlled Disease According to the Investigators' Global Assessment (IGA) | Controlled | 0 Participants |
| LEO 22811 1.5 mg | Participants With Controlled Disease According to the Investigators' Global Assessment (IGA) | Non-controlled | 15 Participants |
| LEO 22811 3.0 mg | Participants With Controlled Disease According to the Investigators' Global Assessment (IGA) | Controlled | 1 Participants |
| LEO 22811 3.0 mg | Participants With Controlled Disease According to the Investigators' Global Assessment (IGA) | Non-controlled | 17 Participants |
Secondary
Participants With Satisfactory Response According to IGA
Satisfactory response was defined as participants classified as Clear or Almost Clear or Mild according to the IGA.
Time frame: At end of treatment (Day 84)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Participants With Satisfactory Response According to IGA | Satisfactory | 2 Participants |
| Placebo | Participants With Satisfactory Response According to IGA | Unsatisfactory | 12 Participants |
| LEO 22811 0.5 mg | Participants With Satisfactory Response According to IGA | Satisfactory | 1 Participants |
| LEO 22811 0.5 mg | Participants With Satisfactory Response According to IGA | Unsatisfactory | 15 Participants |
| LEO 22811 1.5 mg | Participants With Satisfactory Response According to IGA | Satisfactory | 1 Participants |
| LEO 22811 1.5 mg | Participants With Satisfactory Response According to IGA | Unsatisfactory | 14 Participants |
| LEO 22811 3.0 mg | Participants With Satisfactory Response According to IGA | Unsatisfactory | 16 Participants |
| LEO 22811 3.0 mg | Participants With Satisfactory Response According to IGA | Satisfactory | 2 Participants |