Psoriasis Vulgaris
Conditions
Brief summary
Comparison of the efficacy of LEO 90100 foam with Dovobet® ointment in the treatment of psoriasis in Japanese subjects.
Detailed description
A phase 3, national, multi-centre, 4-week, prospective, randomised, controlled, parallel-group, open trial of LEO 90100 foam versus Dovobet® ointment (both treatments containing calcipotriol hydrate plus betamethasone dipropionate) in Japanese subjects with psoriasis vulgaris.
Interventions
DRUGLEO 90100 foam
Once daily topical application of foam from a can to psoriasis lesions. Dose depends on size of lesion.
Once daily topical application of ointment from a tube to psoriasis lesions. Dose depends on size of lesion.
Sponsors
LEO Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Signed and dated informed consent obtained 2. Japanese subjects 3. Aged 20 years or above 4. Clinical diagnosis of psoriasis vulgaris amenable to topical treatment of less than or equal to 30% BSA (excluding psoriasis on the face/genitals/skin folds). 5. A target psoriasis lesion of at least mild severity on the body of a minimum size of 10 cm2 and scoring at least 2 (mild) for each of the clinical signs). The lesion must not be on the scalp, face, genitals or skin folds. 6. Women of childbearing potential must have a negative pregnancy test at Day 1 and agree to use an adequate methods of birth control during the trial. 7. Able to communicate with the (sub)investigator and understand and comply with the requirements of the trial. Key
Exclusion criteria
1. Systemic use of biological treatments with a potential effect on psoriasis vulgaris within the specified time periods prior to randomisation (depending on treatment) 2. Systemic treatments with all therapies other than biological treatments with a potential effect on psoriasis vulgaris within 4 weeks prior to randomisation 3. PUVA therapy, UVB therapy or UVA therapy on the full body or on the target lesion within 4 weeks prior to randomisation 4. Topical treatment of psoriasis on the areas to be treated with trial medication within 2 weeks prior to randomisation 5. Topical treatment of psoriasis on the face, genitals or skin folds with vitamin D3 analogues, potent corticosteroids or immunosuppressants within 2 weeks prior to randomisation 6. Topical treatment of conditions other than psoriasis with vitamin D3 analogues, potent corticosteroids or immunosuppressants within 2 weeks prior to randomisation 7. Initiation or changes of medication that may affect psoriasis vulgaris during the trial 8. Patients with certain disorders or symptoms present on the areas to be treated with trial medication: viral lesions of the skin, infections, skin manifestations, or fragility of skin veins 9. Other inflammatory skin diseases that may confound the evaluation of psoriasis vulgaris 10. Erythrodermic, exfoliative or pustular psoriasis on the areas to be treated with trial medication 11. Planned excessive exposure of areas to be treated with trial medication to either natural or artificial sunlight during the trial. 12. Disorders of calcium metabolism 13. Severe renal insufficiency, severe hepatic disorders or severe heart disease 14. Hypersensitivity to any components of the investigational medicinal products. 15. Cushing's disease or Addison's disease 16. Subjects who have received treatment with any non-marketed drug substance within the 4 weeks prior to randomisation, or longer if for certain biological treatments 17. History of cancer within the last 5 years (except completely cured skin cancer) 18. Current participation in any other interventional clinical trial 19. Previously randomised in this trial 20. Women who are pregnant, wishing to become pregnant or are breast-feeding 21. Chronic alcohol or drug abuse within 12 months prior to screening, or any condition associated with poor compliance 22. Employees of the trial site or any other individuals directly involved with the planning or conduct of the trial, or immediate family members of such individuals
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Improvement Rate for the Target Lesion | End of Week 4 | Overall improvement defined as 'Substantial Resolution' of Clinical Signs or at Least 'Moderately Improved' in the General Change in the Lesion. Substantial resolution' is defined as a clinical score for thickness and scaliness of 0 and a clinical score for redness of 1 or less in the severity of clinical signs of the target lesion. The details of the clinical scores are presented in secondary outcome measure description for 'Change in the total sign score'. Change in the Lesion is a 5 point scale below: * Markedly improved (best outcome) * Moderately improved * Slightly improved * Unchanged * Aggravated (worst outcome) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Improvement Rate for the Target Lesion at Weeks 1 and 2 | End of Weeks 1 and 2 | Substantial resolution of clinical signs or at least 'moderately improved' in the general change in the target lesion. Change in the Lesion is a 5 point scale below: * Markedly improved (best outcome) * Moderately improved * Slightly improved * Unchanged * Aggravated (worst outcome) |
| Change in the Total Sign Score for the Target Lesion From Week 0 to Week 4 | End of Week 4 | The change in the total sign score from Week 0 to Week 4; total sign score is defined as the sum of the scores from the 3 clinical signs (redness, thickness, and scaliness) assessing severity in the target lesion. The severity for each of the 3 clinical signs was recorded according to a 9-point scale that ranges from a score of 0 to 4 in increments of 0.5; the severities are scored from low to high with 0 = none and 4 = severe. The sum of the 3 total sign scores could range from 0 (best) to 12 (worse). The greater the negative value for the change means a better outcome. Negative change denotes a decrease in the score and therefore a decrease in disease severity. |
| Number of Adverse Events | Treatment Emergent Adverse Events were assessed from Day 1 to end of Week 4, if Treatment Emergent Adverse Events were noted, they were followed for an additional 14 days | Number of treatment emergent adverse events (TEAEs). 14-day follow-up of TEAEs was only required if the TEAE was present at the last visit, and was of possible or probable relationship to trial medication. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LEO 90100 Foam calcipotriol hydrate 52.2 µg/g \[equivalent to 50.0 µg/g calcipotriol\] plus betamethasone dipropionate 0.643 mg/g
LEO 90100 foam: Once daily topical application of foam from a can to psoriasis lesions. Dose depends on size of lesion. | 87 |
| Dovobet® Ointment calcipotriol hydrate 52.2 µg/g \[equivalent to 50.0 µg/g calcipotriol\] plus betamethasone dipropionate 0.643 mg/g
Dovobet® ointment: Once daily topical application of ointment from a tube to psoriasis lesions. Dose depends on size of lesion. | 95 |
| Total | 182 |
Baseline characteristics
| Characteristic | Dovobet® Ointment | Total | LEO 90100 Foam |
|---|---|---|---|
| Age, Continuous | 54.8 years STANDARD_DEVIATION 12.9 | 54.5 years STANDARD_DEVIATION 13.2 | 54.2 years STANDARD_DEVIATION 13.6 |
| Race/Ethnicity, Customized Japanese | 95 Participants | 182 Participants | 87 Participants |
| Region of Enrollment Japan | 95 participants | 182 participants | 87 participants |
| Sex: Female, Male Female | 34 Participants | 63 Participants | 29 Participants |
| Sex: Female, Male Male | 61 Participants | 119 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 87 | 0 / 95 |
| other Total, other adverse events | 15 / 87 | 19 / 95 |
| serious Total, serious adverse events | 0 / 87 | 0 / 95 |
Outcome results
Primary
Overall Improvement Rate for the Target Lesion
Overall improvement defined as 'Substantial Resolution' of Clinical Signs or at Least 'Moderately Improved' in the General Change in the Lesion. Substantial resolution' is defined as a clinical score for thickness and scaliness of 0 and a clinical score for redness of 1 or less in the severity of clinical signs of the target lesion. The details of the clinical scores are presented in secondary outcome measure description for 'Change in the total sign score'. Change in the Lesion is a 5 point scale below: * Markedly improved (best outcome) * Moderately improved * Slightly improved * Unchanged * Aggravated (worst outcome)
Time frame: End of Week 4
Population: The primary endpoint was analysed for the full analysis set. Rates of subjects with the event defined by the primary endpoint, 'overall improvement rate' for the target lesion at Visit 4 (end of Week 4), were compared between treatment groups by means of Fisher's exact test. Estimated rates, odds ratio, and its 95% CI were presented, together with the p-value from Fisher's exact test.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LEO 90100 Foam | Overall Improvement Rate for the Target Lesion | 86 Participants |
| Dovobet® Ointment | Overall Improvement Rate for the Target Lesion | 89 Participants |
Comparison: Statistical analysis on the Full Analysis Set (FAS)p-value: 0.1295% CI: [0.68, 49.16]Fisher Exact
Secondary
Change in the Total Sign Score for the Target Lesion From Week 0 to Week 4
The change in the total sign score from Week 0 to Week 4; total sign score is defined as the sum of the scores from the 3 clinical signs (redness, thickness, and scaliness) assessing severity in the target lesion. The severity for each of the 3 clinical signs was recorded according to a 9-point scale that ranges from a score of 0 to 4 in increments of 0.5; the severities are scored from low to high with 0 = none and 4 = severe. The sum of the 3 total sign scores could range from 0 (best) to 12 (worse). The greater the negative value for the change means a better outcome. Negative change denotes a decrease in the score and therefore a decrease in disease severity.
Time frame: End of Week 4
Population: The secondary endpoints were analysed for the full analysis set. For the change in the total sign score, the estimated difference between the treatment groups in the mean change (LEO 90100 foam group - Dovobet® ointment group) was calculated with 95% confidence interval. The treatment difference of the change in the total sign score at Visit 4 was estimated with an ANOVA with treatment as fixed effect.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LEO 90100 Foam | Change in the Total Sign Score for the Target Lesion From Week 0 to Week 4 | -7.09 score on a scale | Standard Deviation 1.48 |
| Dovobet® Ointment | Change in the Total Sign Score for the Target Lesion From Week 0 to Week 4 | -5.98 score on a scale | Standard Deviation 2.03 |
Comparison: FASp-value: <0.00195% CI: [-1.64, -0.59]ANOVA
Secondary
Number of Adverse Events
Number of treatment emergent adverse events (TEAEs). 14-day follow-up of TEAEs was only required if the TEAE was present at the last visit, and was of possible or probable relationship to trial medication.
Time frame: Treatment Emergent Adverse Events were assessed from Day 1 to end of Week 4, if Treatment Emergent Adverse Events were noted, they were followed for an additional 14 days
Population: The analysis of adverse events was based on the safety analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LEO 90100 Foam | Number of Adverse Events | 15 participants |
| Dovobet® Ointment | Number of Adverse Events | 19 participants |
Secondary
Overall Improvement Rate for the Target Lesion at Weeks 1 and 2
Substantial resolution of clinical signs or at least 'moderately improved' in the general change in the target lesion. Change in the Lesion is a 5 point scale below: * Markedly improved (best outcome) * Moderately improved * Slightly improved * Unchanged * Aggravated (worst outcome)
Time frame: End of Weeks 1 and 2
Population: The secondary endpoints were analysed for the full analysis set. The number and percentage of subjects with 'overall improvement' were tabulated for Visits 2 and 3 (end of Weeks 1 and 2) and by treatment group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LEO 90100 Foam | Overall Improvement Rate for the Target Lesion at Weeks 1 and 2 | Week 1 | 61 Participants |
| LEO 90100 Foam | Overall Improvement Rate for the Target Lesion at Weeks 1 and 2 | Week 2 | 83 Participants |
| Dovobet® Ointment | Overall Improvement Rate for the Target Lesion at Weeks 1 and 2 | Week 1 | 46 Participants |
| Dovobet® Ointment | Overall Improvement Rate for the Target Lesion at Weeks 1 and 2 | Week 2 | 77 Participants |
Comparison: End of Week 1 (FAS)p-value: 0.00495% CI: [1.36, 4.6]Fisher Exact
Comparison: End of Week 2 (FAS)p-value: 0.00395% CI: [1.57, 14.97]Fisher Exact