E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Psoriasis is an immunologic disease causing inflammation, scaling and redness of the skin of the skin, located mainly on the scalp, sides of elbows and knees, and the sacral region .. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050576 |
E.1.2 | Term | Psoriasis vulgaris |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to evaluate the safety of once daily use of LEO 90100 in adolescent subjects (aged 12 to < 17 years) with plaque psoriasis on the body and scalp. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the efficacy of once daily use of LEO 90100 in adolescent subjects (aged 12 to < 17 years) with plaque psoriasis on the body and scalp. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adolescent subjects (age 12 to 16 years, 11 months).
• Plaque psoriasis on trunk and/or limbs affecting at least 2% BSA.
• Plaque psoriasis on the scalp affecting at least 10% of total scalp area.
• A total psoriatic involvement on trunk, limbs and scalp not exceeding 30% BSA.
• PGA score of at least mild on trunk and/or limbs at SV1, SV2 and V1.
• PGA score of at least mild on scalp at SV1, SV2 and V1.
• A serum albumin-corrected calcium below the upper reference limit at SV2.
• Female subjects must be of either
• non-childbearing potential, i.e. premenarchal or have a confirmed clinical history of sterility (e.g. the subject is without a uterus or has tubal litigation) or,
• child-bearing potential provided there is a confirmed negative pregnancy test prior to trial treatment to rule out pregnancy.
• Female subjects of child-bearing potential must be willing to use highly effective contraception at trial entry and until completion.
30 evaluable subjects without adrenal suppression at baseline will undergo an ACTH-challenge test (Visit 3) and PK assessments (Visit 2 and Visit 3).
The ACTH-challenge test as well as PK assessments will only be performed at assigned sites and countries.
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E.4 | Principal exclusion criteria |
• A history of hypersensitivity to any component of LEO 90100.
• Systemic treatment with biological therapies (marketed or not marketed), with a possible effect on scalp and/or body psoriasis within the following time period prior to V1 and during the trial:
a. etanercept – within 4 weeks prior to V1
b. adalimumab, infliximab – within 2 months prior to V1
c. ustekinumab – within 4 months prior to V1
d. experimental products – within 4 weeks/5 half-lives (whichever is longer) prior to V1
• Systemic treatment with therapies other than biologicals, with a possible effect on scalp and/or body psoriasis (e.g. methotrexate, retinoids, immunosuppressants) within 4 weeks prior to V1 or during the trial.
• PUVA therapy within 4 weeks prior to V1.
• UVB therapy within 2 weeks prior to V1 or during the trial.
• Any topical treatment on the scalp and body including corticosteroids and vitamin D (except for emollients and non-steroid medicated shampoos) within 2 weeks prior to V1 or during the trial.
• Systemic calcium, vitamin D supplementation > 400 IU/day, antacids, diuretics, antiepileptics, diphosphonates or calcitonin within 4 weeks prior to SV2 or during the trial. (note: stable dose of vitamin D supplementation ≤ 400 IU/day is permitted provided there are no dose adjustments during the study period).
Additional exclusion criteria for subjects undergoing HPA axis testing:
A history of serious allergy, allergic asthma or serious allergic skin rash.
Known or suspected hypersensitivity to any component of CORTROSYN® (including ACTH/cosyntropin/tetracosactide)
Systemic treatment with corticosteroids (including inhaled and nasal steroids) within 12 weeks prior to SV2 or during the trial.
Oestrogen therapy (including contraceptives) or any other medication known to affect cortisol levels or HPA axis integrity within 4 weeks prior to SV2 or during the trial.
Enzymatic inductors (e.g., barbiturates, phenytoin, rifampicin) within 4 weeks prior to SV2 or during the trial.
Systemic or topical cytochrome P450 inhibitors (e.g., ketoconazole, itraconazole,metronidazole) within 4 weeks prior to SV2 or during the trial. Topical ketoconazole within 2 weeks prior to SV2.
Hypoglycemic sulfonamides within 4 weeks prior to SV2 or during the trial.
Antidepressive medications within 4 weeks prior to SV2 or during the trial.
Known or suspected endocrine disorder that may affect the results of the ACTH challenge test.
Clinical signs or symptoms of Cushing’s disease or Addison’s disease.
Subjects with diabetes mellitus.
Known or suspected cardiac condition.
Not following nocturnal sleep patterns.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Adverse events (AEs)
• Subjects with serum cortisol concentration of ≤18 mcg/dl at 30 minutes after ACTH-challenge at Week 4
• Change in albumin-corrected serum calcium from baseline (SV2) to Week 4
• Change in calcium excretion from baseline (SV2) to Week 4 in 24-hour urine
• Change in calcium:creatinine ratio from baseline (SV2) to Week 4 in 24-hour urine
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Subjects with serum cortisol concentration of ≤18 mcg/dl at both 30 and 60 minutes after ACTH-challenge at Week 4
• Change in calcium:creatinine ratio from baseline (SV2) to Week 4 in spot urine
• Subjects with ‘treatment success’ (i.e., ‘clear’ or ‘almost clear’ for subjects with at least ‘moderate’ disease at baseline, ‘clear’ for subjects with ‘mild’ disease at baseline) according to the physician´s global assessment of disease severity on the body at Week 4
• Subjects with ‘treatment success’ (i.e., ‘clear’ or ‘almost clear’ for subjects with at least ‘moderate’ disease at baseline, ‘clear’ for subjects with ‘mild’ disease at baseline) according to the physician´s global assessment of disease severity on the scalp at Week 4
• Percentage change in psoriasis area and severity index (PASI) from baseline (V1) to Week 4
• Subjects with ‘treatment success’ (i.e., ‘clear’ or ‘very mild) according to the subject´s global assessment of disease severity on the body at Week 4
• Subjects with ‘treatment success’ (i.e., ‘clear’ or ‘very mild) according to the subject´s global assessment of disease severity on the scalp at Week 4
• Change in itch as assessed by the Visual Analogue Scale (VAS) from baseline (V1) to Week 4
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Netherlands |
Poland |
Romania |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |