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 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
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 |
To Compare the efficacy of crisaborole ointment 2%, administered QD or BID relative to the corresponding vehicle (QD or BID), on Total Sign Score (TSS) assessment in target lesions, in the treatment of mild to moderate AD in adults (cohort 1) and paediatrics (cohort 2). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of crisaborole ointment 2% BID relative to crisaborole ointment 2% QD, on TSS assessment in target lesions, in the treatment of mild to moderate AD in adults (cohort 1) and paediatrics (cohort 2). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female participants ages:
- Cohort 1: >=12 years at the time of consent;
- Cohort 2: 2 years to under 12 years old at the time of consent.
- Participants who had confirmed clinical diagnosis of active AD at screening and baseline/Day 1 according to Hanifin and Rajka criteria and who had at least 6 months history prior to screening visit that had been clinically stable for > 1 month.
- Participants who had a global Investigator Static Global Assessment (ISGA) of 2 (mild) or 3 (moderate)at baseline/Day 1 visit.
- Participants who had AD lesions on upper limbs, lower limbs or ventral of the body trunk and a body surface area (BSA) covered with AD of at least 1.0% and not > 30% at baseline/Day 1, excluding scalp, genitals and groin area. The presence of AD on these areas (scalp, genitals and groin area) was not exclusionary, but was not to be included in the calculation for coverage of BSA with AD.
- Participants who had 2 lesions of AD at least 3 cm x 3 cm with identical lesion ISGA = 3 (moderate) for each lesion. These AD lesions were to be at least 10 cm apart. The target lesions were not to be on the face, neck, scalp, axilla, genitals, groin area, palms, dorsal of the hands, dorsal of the body trunk and soles. In addition, 2 AD areas on the same limb were not to be selected as the target lesions. (Note: When possible, AD areas on the bilateral [left/right] area were to be selected as target lesions). |
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E.4 | Principal exclusion criteria |
- Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that could have increased the risk associated with study participation or study drug administration or could have interfered with the interpretation of study results and in the judgement of the investigator, would have made the participant inappropriate for entry into this study.
- History of angioedema or anaphylaxis to topical products or known sensitivity to any of the components of crisaborole ointment 2%.
- Participants had previous treatment with any topical or systemic phosphodiesterase 4 inhibitor.
- Participants who had undergone treatment for any type of cancer (except squamous cell carcinoma, basal cell carcinoma or carcinoma in situ of the skin, curatively treated with surgical excision only). |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change from baseline in TSS in target lesions treated with crisaborole ointment or vehicle on Day 15 in each regimen (Regimen 1: QD, Regimen 2: BID) for each cohort |
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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) |
- Change from baseline in TSS in target lesions treated with crisaborole ointment or vehicle on Day 15 in each regimen for each cohort
- Change from baseline in TSS in target lesions treated with crisaborole ointment or vehicle on Day 8 in each regimen for each cohort
- Change from baseline in ISGA in target lesions treated with crisaborole ointment or vehicle at each visit up to Day 15 in each regimen for each cohort
- Change from baseline in pruritus assessments in target lesions treated with crisaborole ointment or vehicle at each day up to Day 15 in each regimen using the following scales:
- Cohort 1: Peak Pruritus, NRS (Age>=12 years), Cohort 2: Itch severity scale (Age 6-11 years) Self-Report, Cohort 2: Caregiver reported itch severity NRS (Age 2-11 years)
- Incidence of TEAEs and SAEs in each regimen for each cohort |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- At Day 8
- At Day 15
- At each visit up to Day 15
- At each visit up to Day 15
- All visits |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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.8.9.2 | In all countries concerned by the trial months | 6 |