Safety and Efficacy of LEO 80185 Topical Suspension in Adolescent Subjects (Aged 12 to 17) With Scalp Psoriasis

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety and efficacy of once daily use of LEO 80185 topical suspension in adolescent subjects (aged 12 to 17 years) with scalp psoriasis. LEO 80185 topical suspension has marketing approval in many countries under the brand names Taclonex Scalp® Topical Suspension and Xamiol® gel for the treatment of scalp psoriasis in adults. No studies have been performed in subjects younger than 18 years.

Official Title
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Effect of Calcipotriol Plus Betamethasone Dipropionate Topical Suspension on the HPA Axis and Calcium Metabolism in Adolescent Subjects (Aged 12 to 17 Years) With Scalp Psoriasis

Conditions
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Scalp Psoriasis

Intervention / Treatment
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* Drug: LEO 80185 (Taclonex® Scalp topical suspension/Xamiol® gel)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent given by parent(s) or legal guardian following their receipt of verbal and written information about the study Subjects will receive verbal and written information and will provide written assent to the study Any race or ethnicity Clinical signs of psoriasis vulgaris on trunk and/or limbs, or earlier diagnosed with psoriasis vulgaris on trunk and/or limbs At Screening Visit 2 and Visit 1 a clinical diagnosis of scalp psoriasis which is: amenable to topical treatment with a maximum of 60 g of study medication per week, and of an extent of more than or equal to 20% of the scalp area of at least moderate severity according to the investigator's global assessment Subjects with a normal HPA axis function at SV2 including serum cortisol concentration above 5 mcg/dl before ACTH challenge and serum cortisol concentration above 18 mcg/dl 30 minutes after ACTH challenge A serum albumin-corrected calcium below the upper reference limit at Screening Visit 2 Females of child-bearing potential must have a negative urine pregnancy test result and must agree to use a highly effective method of contraception (abstinence is an acceptable method). Exclusion Criteria (summary): A history of serious allergy, allergic asthma or serious allergic skin rash Known or suspected hypersensitivity to any medication (including ACTH/cosyntropin/tetracosactide) or to any component of the LEO 80185 topical suspension or CORTROSYN Systemic treatment with corticosteroids (including inhaled and nasal steroids) within 12 weeks prior to Screening Visit 2 or during the study Topical treatment with corticosteroids within 2 weeks prior to Screening Visit 2 or during the study Oestrogen therapy (including contraceptives) or any other medication known to affect cortisol levels or HPA axis integrity within 4 weeks prior to Screening Visit 2 or during the study Enzymatic inductors (e.g., barbiturates, phenytoin, rifampicin)or cytochrome P450 inhibitors (e.g., ketoconazole, itraconazole, metronidazole) within 4 weeks prior to Screening Visit 2 or during the study. Topical ketoconazole 2 weeks prior to Screening Visit 2 Hypoglycemic sulfonamides or Antidepressive medications within 4 weeks prior to Screening Visit 2 or during the study Known or suspected endocrine disorder that may affect the results of the ACTH challenge test Systemic treatment with biological therapies (marketed or not marketed), with a possible effect on scalp psoriasis within the following time period prior to Visit 1 and during the study within 4 weeks/5 half-lives (whichever is longer) prior to Visit 1 Systemic treatment with therapies other than biologicals, with a possible effect on scalp psoriasis (e.g., retinoids, immunosuppressants, PUVA) within 4 weeks prior to Visit 1 (Day 0) or during the study Planned initiation of, or changes to, concomitant medication that could affect scalp psoriasis (e.g., betablockers, chloroquine, lithium, ACE inhibitors) during the study Other inflammatory skin diseases that may confound the evaluation of scalp psoriasis Known or suspected disorders of calcium metabolism associated with hypercalcaemia

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: LEO 80185 (Taclonex® Scalp topical suspension/ Xamiol® gel)<br> | Drug: LEO 80185 (Taclonex® Scalp topical suspension/Xamiol® gel)<br>* Topical suspension applied once daily for up to 8 weeks<br>* Other names: LEO 80185 topical suspension;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Adverse Drug Reactions (ADRs) | Adverse events for which the investigator did not describe the causal relationship to IP as not related | Throughout trial, up to 8 weeks | 
| Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After ACTH-challenge at Week 4 | Adrenal function can be measured by injecting a synthetic subunit of ACTH (Adrenocorticotropic hormone), and then measure the production of cortisol by the adrenal glands in response to this at 30 minutes after the injection. | Week 4 | 
| Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 Minutes After ACTH-challenge at Week 8 | Adrenal function can be measured by injecting a synthetic subunit of ACTH Adrenocorticotropic hormone), and then measure the production of cortisol by the adrenal glands in response to this at 30 minutes after the injection. | week 8 | 
| Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 and 60 Minutes After ACTHchallenge at Week 4. | Adrenal function can be measured by injecting a synthetic subunit of ACTH Adrenocorticotropic hormone), and then measure the production of cortisol by the adrenal glands in response to this at 30 and 60 minutes after the injection. | week 4 | 
| Subjects With Serum Cortisol Concentration of ≤18 mcg/dl at 30 and 60 Minutes After ACTH-challenge at Week 8. | Adrenal function can be measured by injecting a synthetic subunit of ACTH (Adrenocorticotropic hormone), and then measure the production of cortisol by the adrenal glands in response to this at 30 and 60 minutes after the injection. | week 8 | 
| Change in Albumincorrected Serum Calcium From Baseline (SV2) to Week 4, Week 8, and End of Treatment. | Change in albumincorrected serum calcium from Baseline (SV2 = screening visit 2) to Week 4, Week 8, and end of treatment. | Baseline and week 4 | 
| Change in Albumincorrected Serum Calcium From Baseline (SV2) to Week 4, Week 8, and End of Treatment. | Change in albumincorrected serum calcium from Baseline (SV2 = screening visit 2) to Week 4, Week 8, and end of treatment. | Baseline and week 8 | 
| Change in Albumincorrected Serum Calcium From Baseline (SV2) to Week 4, Week 8, and End of Treatment. | Change in albumincorrected serum calcium from Baseline (SV2 = screening visit 2) to Week 4, Week 8, and end of treatment. | Baseline and end of treatment (up to 8 weeks) | 
| Change in 24-hour Urinary Calcium Excretion From Baseline (SV2) to Week 4, Week 8, and End of Treatment. | Change in 24-hour urinary calcium excretion from Baseline (SV2 = screening visit 2) to Week 4, Week 8, and end of treatment. | Baseline and week 4 | 
| Change in 24-hour Urinary Calcium Excretion From Baseline (SV2) to Week 4, Week 8, and End of Treatment. | Change in 24-hour urinary calcium excretion from Baseline (SV2 = screening visit 2) to Week 4, Week 8, and end of treatment. | Baseline and week 8 | 
| Change in 24-hour Urinary Calcium Excretion From Baseline (SV2) to Week 4, Week 8, and End of Treatment. | Change in 24-hour urinary calcium excretion from Baseline (SV2 = screening visit 2) to Week 4, Week 8, and end of treatment. | Baseline and end of treatment (up to 8 weeks) | 
| Change in Urinary Calcium:Creatinine Ratio From Baseline (SV2) to Week 4, Week 8 and, End of Treatment. | Change in urinary calcium:creatinine ratio from Baseline (SV2 = screening visit 2) to Week 4, Week 8 and, end of treatment. | Baseline and week 4 | 
| Change in Urinary Calcium:Creatinine Ratio From Baseline (SV2) to Week 4, Week 8 and, End of Treatment. | Change in urinary calcium:creatinine ratio from Baseline (SV2 = screening visit 2) to Week 4, Week 8 and, end of treatment. | Baseline and week 8 | 
| Change in Urinary Calcium:Creatinine Ratio From Baseline (SV2) to Week 4, Week 8 and, End of Treatment. | Change in urinary calcium:creatinine ratio from Baseline (SV2 = screening visit 2) to Week 4, Week 8 and, end of treatment. | Baseline and end of treatment (up to 8 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Plasma PTH From Baseline (SV2) to Week 4 and Week 8 | Change in plasma PTH (parathyroid hormone) from Baseline (SV2 = screening visit 2) to Week 4 and Week 8 | Baseline and week 4 | 
| Change in Plasma PTH From Baseline (SV2) to Week 4 and Week 8 | Change in plasma PTH (parathyroid hormone) from Baseline (SV2 = screening visit 2) to Week 4 and Week 8 | Baseline and week 8 | 
| Subjects With Controlled Disease (i.e., Clear or Almost Clear) According to the Investigator's Global Assessment (IGA) of Disease Severity at Weeks 2, 4, 8, and End of Treatment. | Disease severity of the scalp psoriasis as assessed by the 6-point scale IGA, based on the condition of the disease at the time of evaluation. The IGA scale: 1 = clear, 2 = almost clear, 3 = mild, 4 = moderate, 5 = severe, and 6 = very severe. | week 2 | 
| Subjects With Controlled Disease (i.e., Clear or Almost Clear) According to the Investigator's Global Assessment (IGA) of Disease Severity at Weeks 2, 4, 8, and End of Treatment. | Disease severity of the scalp psoriasis as assessed by the 6-point scale IGA, based on the condition of the disease at the time of evaluation. | week 4 | 
| Subjects With Controlled Disease (i.e., Clear or Almost Clear) According to the Investigator's Global Assessment (IGA) of Disease Severity at Weeks 2, 4, 8, and End of Treatment. | Disease severity of the scalp psoriasis as assessed by the 6-point scale IGA, based on the condition of the disease at the time of evaluation. | week 8 | 
| Subjects With Controlled Disease (i.e., Clear or Almost Clear) According to the Investigator's Global Assessment (IGA) of Disease Severity at Weeks 2, 4, 8, and End of Treatment. | Disease severity of the scalp psoriasis as assessed by the 6-point scale IGA, based on the condition of the disease at the time of evaluation. | End of treatment | 
| Percentage Change in Total Sign Score (TSS; Sum of Severity Scores for Each Individual Clinical Sign, Redness, Thickness, and Scaliness) From Baseline to Weeks 2, 4, 8, and End of Treatment. | Investigator assessment of scalp psoriasis lesions in terms of the three clinical signs: redness, thickness, and scaliness. Each clinical sign, a single score(ranging from 0 to 4), reflecting the average severity of all psoriatic lesions on the scalp, were determined. The sum of the three scores (redness, thickness, and scaliness) constitutes the Total Sign Score of the psoriasis on scalp, ranging from 0 (best possible outcome) to 12 points (worst possible outcome). | week 2 | 
| Percentage Change in Total Sign Score (TSS; Sum of Severity Scores for Each Individual Clinical Sign, Redness, Thickness, and Scaliness) From Baseline to Weeks 2, 4, 8, and End of Treatment. | Investigator assessment of scalp psoriasis lesions in terms of the three clinical signs: redness, thickness, and scaliness. Each clinical sign, a single score (ranging from 0 to 4), reflecting the average severity of all psoriatic lesions on the scalp, were determined. The sum of the three scores (redness, thickness, and scaliness) constitutes the Total Sign Score of the psoriasis on scalp, ranging from 0 (best possible outcome) to 12 points (worst possible outcome). | Baseline and week 4 | 
| Percentage Change in Total Sign Score (TSS; Sum of Severity Scores for Each Individual Clinical Sign, Redness, Thickness, and Scaliness) From Baseline to Weeks 2, 4, 8, and End of Treatment. | Investigator assessment of scalp psoriasis lesions in terms of the three clinical signs: redness, thickness, and scaliness. Each clinical sign, a single score (ranging from 0 to 4), reflecting the average severity of all psoriatic lesions on the scalp, were determined. The sum of the three scores (redness, thickness, and scaliness) constitutes the Total Sign Score of the psoriasis on scalp, ranging from 0 (best possible outcome) to 12 points (worst possible outcome). | Baseline and week 8 | 
| Percentage Change in Total Sign Score (TSS; Sum of Severity Scores for Each Individual Clinical Sign,Redness, Thickness, and Scaliness) From Baseline to Weeks 2, 4, 8, and End of Treatment. | Investigator assessment of scalp psoriasis lesions in terms of the three clinical signs: redness, thickness, and scaliness. Each clinical sign, a single score (ranging from 0 to 4), reflecting the average severity of all psoriatic lesions on the scalp, were determined. The sum of the three scores (redness, thickness, and scaliness) constitutes the Total Sign Score of the psoriasis on scalp, ranging from 0 (best possible outcome) to 12 points (worst possible outcome). | Baseline and end of treatment (up to 8 weeks) | 
| Subjects With Controlled Disease (Defined as Clear or Very Mild) According to the Patient's Global Assessment of Disease Severity at Weeks 2, 4, 8, and End of Treatment. | Disease severity of the scalp psoriasis as assessed by the 5-point scale, Patient's Global Assessment of Disease Severity, based on the condition of the disease at the time of evaluation. The scale scores are based on the following; 1 = clear, 2 = very mild, 3 = mild, 4 = moderate, 5 = severe. | week 2 | 
| Subjects With Controlled Disease (Defined as Clear or Very Mild) According to the Patient's Global Assessment of Disease Severity at Weeks 2, 4, 8, and End of Treatment. | Disease severity of the scalp psoriasis as assessed by the 5-point scale, Patient's Global Assessment of Disease Severity, based on the condition of the disease at the time of evaluation. | week 4 | 
| Subjects With Controlled Disease (Defined as Clear or Very Mild) According to the Patient's Global Assessment of Disease Severity at Weeks 2, 4, 8, and End of Treatment. | Disease severity of the scalp psoriasis as assessed by the 5-point scale, Patient's Global Assessment of Disease Severity, based on the condition of the disease at the time of evaluation. | week 8 | 
| Subjects With Controlled Disease (Defined as Clear or Very Mild) According to the Patient's Global Assessment of Disease Severity at Weeks 2, 4, 8, and End of Treatment. | Disease severity of the scalp psoriasis as assessed by the 5-point scale, Patient's Global Assessment of Disease Severity, based on the condition of the disease at the time of evaluation. | End of treatment |