E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Psoriasis of the scalp and body |
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E.1.1.1 | Medical condition in easily understood language |
Psoriasis of the scalp and body |
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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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037153 |
E.1.2 | Term | Psoriasis |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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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 calcipotriol (50 mcg/g) plus betamethasone (0.5 mg/g) (as dipropionate) gel in adolescent subjects (aged 12 to 16 years, 11 months) with scalp and body psoriasis. |
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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 calcipotriol (50 mcg/g) plus betamethasone (0.5 mg/g) (as dipropionate) gel in adolescent subjects (aged 12 to 16 years, 11 months) with scalp and body psoriasis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria for All Subjects:
1. Signed informed consent given by parent(s), or legal guardian(s), or by the subject (according to national law) following their receipt of verbal and written information about the trial.
2. Subjects will receive verbal and written information and will provide written assent to the trial.
3. Subjects 12 to 16 years, 11 months of age.
4. Either sex.
5. Any race or ethnicity.
6. Clinical signs of psoriasis vulgaris on both the scalp and body (trunk and/or limbs).
7. A serum albumin-corrected calcium below the upper reference limit at SV2.
8. Females of child-bearing potential must have a negative urine pregnancy test result and must agree to use a highly effective method of contraception during the trial. Highly effective methods are defined as ones which result in a low failure rate (less than 1% per year) such as progestin-only formulations (implants, injectables, or “mini-pill” in combination with a barrier method), some intra-uterine devices, double barrier methods (eg. cervical cap and condom), tubal ligation/section, sexual abstinence or vasectomised partner. The patients must have used the contraceptive method for at least 1 month prior to the pregnancy test at SV2, and must continue using the contraceptive method for at least 1 week after the last application of investigational product. A female is defined as not of child-bearing potential if she is premenarchal, postmenopausal or surgically sterile (hysterectomy or bilateral ovariectomy).
9. Subjects fulfilling national requirements/law for participation in this trial.
Additional Inclusion Criteria for Subjects Performing HPA Axis
and PK Assessments (assigned U.S. sites only):
10. At SV2 and Visit 1, a clinical diagnosis of scalp and body (trunk and/or limbs) psoriasis which is:
a. of an extent of 10 to 35% of the body surface area (excluding psoriatic lesions of the face and sensitive areas), and
b. of at least moderate severity according to the investigator’s global assessment of disease severity on the body
11. At SV2 and Visit 1, a clinical diagnosis of scalp psoriasis which is:
a. more than or equal to 20% of the scalp area, and
b. of at least moderate severity according to the investigator’s global assessment of disease severity on the scalp.
12. 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.
13. At Visit 1, weighing at least 30kg
Additional Inclusion Criteria for Subjects Not Performing HPA
Axis and PK Assessments:
14. At SV2 and Visit 1, a clinical diagnosis of body (trunk and/or limbs) psoriasis which is:
a. more than or equal to 3% of the body surface area (excluding psoriatic lesions of the face and sensitive areas), and
b. of at least mild severity according to the investigator’s global assessment of
disease severity on the body.
15. At SV2 and Visit 1, a clinical diagnosis of scalp psoriasis which is:
a. more than or equal to 10% of the scalp area, and
b. of at least mild severity according to the investigator’s global assessment of
disease severity on the scalp, and
c. for subjects aged 12 to < 15 years with a BSA ≤ 1.3 m2, amenable to topical
treatment with a maximum of 55 g of investigational product per week, and
d. for subjects aged 12 to < 15 years with a BSA > 1.3 m2, amenable to topical
treatment with a maximum of 75 g of investigational product per week, and
e. for subjects aged > 15 years with a BSA ≤ 1.7 m2, amenable to topical treatment with a maximum of 75 g of investigational product per week, and
f. for subjects aged > 15 years with a BSA > 1.7 m2, amenable to topical treatment with a maximum of 100 g of investigational product per week. |
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E.4 | Principal exclusion criteria |
1. A history of hypersensitivity to any component of the LEO 80185 gel
2. 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 Visit 1 and during the trial:
a. etanercept – within 4 weeks prior to Visit 1
b. adalimumab, infliximab – within 2 months prior to Visit 1
c. ustekinumab – within 4 months prior to Visit 1
d. experimental products – within 4 weeks/5 half-lives prior to Visit 1
3. Systemic treatment with therapies other than biologicals, with a possible effect on scalp and/or body psoriasis (e.g., retinoids, immunosuppressants, PUVA) within 4 weeks prior to Visit 1 (Day 0) or during the trial.
4. UVB therapy within 2 weeks prior to Visit 1 or during the trial.
5. Any topical treatment on the scalp and body including corticosteroids (except for emollients and non-steroid medicated shampoos) within 2 weeks prior to Visit 1 or during the trial.
6. Systemic calcium, vitamin D supplementation > 400 IU/day, antacids, diuretics, antiepileptics, diphosphonates or calcitonin within 4 weeks prior to SV2 or during the trial.
7. Planned initiation of, or changes to, concomitant medication that could affect psoriasis (e.g., betablockers, chloroquine, lithium, ACE inhibitors) during the trial.
8. Current diagnosis of guttate, erythrodermic, exfoliative or pustular psoriasis.
9. Subjects with any of the following conditions present on the treatment areas on scalp and/or body: viral (e.g., herpes or varicella) lesions of the skin, fungal and bacterial skin infections, parasitic infections, skin manifestations in relation to syphilis or tuberculosis, rosacea, acne vulgaris, acne rosacea, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, ulcers and wounds.
10. Other inflammatory skin diseases that may confound the evaluation of scalp and/or body psoriasis.
11. Planned excessive exposure to sun during the trial that may affect scalp and/or body psoriasis.
12. Known or suspected severe renal insufficiency or severe hepatic disorders.
13. Known or suspected disorders of calcium metabolism associated with hypercalcaemia.
14. Any clinically significant abnormality following review of screening laboratory tests (blood and urine samples), physical examination or blood pressure/heart rate measurement performed at SV2.
15. Current participation in any other interventional clinical trial.
16. Previously treated with LEO80185 in this trial.
17. 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 a month prior to SV1 or longer, if the class of substance required a longer wash-out as defined above (e.g., biological treatments).
18. Subjects or parent(s) or legal guardian known or suspected of being unlikely to comply with the Clinical Trial Protocol (e.g., alcoholism, drug dependency or psychotic state).
19. Females who are pregnant, or of child-bearing potential and wishing to become pregnant during the trial, or who are breast-feeding.
20. Females of child-bearing potential with positive pregnancy test at SV2.
21. Subject (or their partner) not using an adequate method of contraception according to national requirements.
22. A history of serious allergy, allergic asthma or serious allergic skin rash.
23. Known or suspected hypersensitivity to any component of CORTROSYN® (including ACTH/cosyntropin/tetracosactide)
24. Systemic treatment with corticosteroids (including inhaled and nasal steroids) within 12 weeks prior to SV2 or during the trial.
25. Oestrogen therapy (including contraceptives) or any other medication known to affect cortisol levels levels or HPA axis integrity within 4 weeks prior to SV2 or during the trial.
26. Enzymatic inductors (e.g., barbiturates, phenytoin, rifampicin) within 4 weeks prior to SV2 or during the trial.
27. Systemic or topical cytochrome P450 inhibitors (e.g., ketoconazole, itraconazole, metronidazole) within 4 weeks prior to SV2 or during the trial. Topical ketoconazole 2 weeks prior to SV2.
28. Hypoglycemic sulfonamides within 4 weeks prior to SV2 or during the trial.
29. Antidepressive medications within 4 weeks prior to SV2 or during the trial.
30. Known or suspected endocrine disorder that may affect the results of the ACTH challenge test.
31. Clinical signs or symptoms of Cushing’s disease or Addison’s disease.
32. Subjects with diabetes mellitus.
33. Known or suspected cardiac condition.
34. Not following nocturnal sleep patterns.
35. Topical treatment on the face and/or sensitive areas (armpits, groin, under the breasts and in other skin folds around the genitals and buttocks) with potent or very potent (WHO groups III-IV) corticosteroids within 2 weeks prior to Visit 1 or during the trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Adverse drug reactions (ADRs)
• Subjects with serum cortisol concentration of ≤18 mcg/dl at 30 minutes after ACTH-challenge at Week 4 and at Week 8
• Change in albumin-corrected serum calcium from baseline (SV2) to Week 4, Week 8, and end of treatment
• Change in 24-hour urinary calcium excretion from baseline (SV2) to Week 4, Week 8, and end of treatment
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Adverse drug reactions (ADRs)
• Subjects with serum cortisol concentration of ≤18 mcg/dl at 30 minutes after ACTH-challenge at Week 4 and at Week 8
• Change in albumin-corrected serum calcium from baseline (SV2) to Week 4, Week 8, and end of treatment
• Change in 24-hour urinary calcium excretion from baseline (SV2) to Week 4, Week 8, and end of treatment
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E.5.2 | Secondary end point(s) |
• Adverse events (AEs)
• Subjects with serum cortisol concentration of ≤18 mcg/dl at both 30 and 60 minutes after ACTH-challenge at Week 4 and at Week 8
• Change in urinary calcium:creatinine ratio from baseline (SV2) to Week 4 and Week 8
• Change in serum alkaline phosphate (ALP) from baseline (SV2) to Week 4 and Week 8
• The following PK parameters calculated at Week 4 for each assayed compound:
o AUC 0-t
o AUC 0-∞
o C max
o T max
o T 1/2
• Subjects with “Controlled disease” (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 investigator’s global assessment of
• Percentage change in PASI from baseline to end of treatment.
• Subjects with “Controlled disease” (i.e., “Clear” or “Very mild”) according to the patient’s global assessment of disease severity on the body at end of treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Adverse events (AEs)
• Subjects with serum cortisol concentration of ≤18 mcg/dl at both 30 and 60 minutes after ACTH-challenge at Week 4 and at Week 8
• Change in urinary calcium:creatinine ratio from baseline (SV2) to Week 4 and Week 8
• Change in serum alkaline phosphate (ALP) from baseline (SV2) to Week 4 and Week 8
• PK parameters calculated at Week 4 for each assayed compound.
• Subjects with “Controlled disease” (i.e., “Clear” or “Almost clear”) according to the investigator’s global assessment of
• Percentage change in PASI from baseline to end of treatment.
• Subjects with “Controlled disease” (i.e., “Clear” or “Very mild”) according to the patient’s global assessment of disease severity on the body at end of treatment. |
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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 | No |
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.8.3 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Australia |
Canada |
France |
Germany |
New Zealand |
Poland |
Romania |
United Kingdom |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 28 |