Validation of a Novel Composite of Skin Biomarkers as a Primary Outcome Measure for Evaluating the Safety of Treatments for Atopic Dermatitis: a Randomized Controlled Trial (Phase 2) Comparing the Effects of Crisaborole 2% Ointment to Betamethasone Valerate 0.1% Cream on Skin Structure and Function in Participants With Atopic Dermatitis.
Overview
- Phase
- Phase 2
- Intervention
- crisaborole (2%) ointment
- Conditions
- Atopic Eczema/Dermatitis (Non-Specific)
- Sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- Change in Epidermal Thickness
- Status
- Completed
- Last Updated
- 9 months ago
Overview
Brief Summary
The study aims to investigate two new non-invasive technologies for assessing skin properties to identify and validate a range of safety biomarkers that may be considered useful as primary outcome measures for evaluating the safety of topical treatments in atopic dermatitis. The method of assessing these biomarker technologies will be to determine whether twice daily treatment with crisaborole (2%) ointment, compared to betamethasone valerate (0.1%) cream, for up to 4 weeks, may cause skin structure or function changes, like skin atrophy, in patients with atopic dermatitis (AD).
Detailed Description
The first-line drug treatment for mild-moderate AD are currently topical corticosteroids (TCS) with recognized efficacy. However, their prolonged or inappropriate use, can lead to local adverse effects. Side-effects of topical corticosteroids comprise a variety of skin changes in the sense of skin atrophy thinning of the skin and in some cases development of telangiectasia, spontaneous scars, folliculitis, striae distensae (stretch marks), contact dermatitis, acne or rosacea depending on potency, galenic formulation, patient age and body area to which the medication will be applied, exposure time. Assessing the safety (local adverse effects) of current or new treatments and new treatment approaches using existing treatments through noninvasively monitor on possible early skin (subclinical) changes associated with the local clinical adverse effects of treatment may be an effective step for an enhanced AD treatment management. Primary Aim: To further develop and validate two new non-invasive technologies for the assessment of early sub-clinical skin changes associated with adverse effects and to derive an optimum panel of safety biomarkers for use in future clinical trials of topical anti-inflammatory treatments. The safety of two topical anti-inflammatory treatments for AD will be compared in this clinical trial, with a focus on early sub-clinical signs: crisaborole 2% ointment and betamethasone valerate 0,1% cream. Step 1 involves the collection of data on the early sub-clinical skin changes using the non-invasive technologies: OCT and FTIR spectroscopy. The data from this study will then be used to identify and refine biophysical biomarkers of skin atrophy and skin barrier disruption in steps 2 and 3. Secondary Aim: To determine the relative local skin effects of crisaborole (2%) ointment compared to a potent and moderately potent TCS in participants with mild to moderate AD. The focus is on 'early biomarkers' of 'local skin changes'and not clinical efficacy, which has been established in previous trials. Rationale for selecting the two comparators are related to prescription behaviors in UK (Betamethasone valerate 0,1% cream) and with no reported TCS-like local adverse effects profile (crisaborole 2% ointment)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Volunteers with AD defined according to the UK working party diagnostic criteria
- •Male or female aged 18-65 years old at baseline (Visit 1)
- •Volunteer understands the purpose, modalities and potential risk of the trial
- •Participants able to read and understand English
- •Participants willing to sign the informed consent
Exclusion Criteria
- •Participants with a known allergy/hypersensitivity to any of the excipients of the trial preparations.
- •Participants with acne, suntan, birth marks, multiple nevi, tattoos, blemishes or dense body hair that obstruct the test areas.
- •Investigator assessment of eczema severity at the treatment (anatomical) sites is almost clear or greater (score ≥1) based on the Investigators static global assessment scale at screening and baseline. At the start of the study the skin of the test sites (forearms) will therefore be clear (0) of the signs of eczema
- •Participants with a condition that in the opinion of the investigator contradicts participation in the study.
- •Pregnant female participants; breastfeeding female participants; and female participants of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
- •Use of any topical product on the test areas within 7 days prior to Baseline/Day 1, including cosmetic moisturizers and sunscreen. Participants using any topical products on the test areas within 7 days at the screening visit will be eligible if they are willing and able to wash-out these products for 7 days in total and for the duration of the trial. Such participants will be potentially eligible at screening and will be confirmed as eligible if adequate washout is confirmed at visit
- •Use of moisturizers and/or sunscreen is permitted during the study to manage dry skin and sun exposure in areas surrounding but not on or overlapping the test areas.
- •Participants who have used a tanning bed within 28 days of baseline (visit 1). Participants who have used a sunbed within 28 days at the screening visit will be eligible if they are willing and able to wash-out for 28 days in total and for the duration of the trial. Such participants will be potentially eligible at screening and will be confirmed as eligible if adequate washout is confirmed at visit
- •Participants who have used any medication that could interfere with the trial aim prior to the start of the study (baseline/visit 1). Participants using such medication at the screening visit will be eligible if they are willing and able to wash-out these treatments for the applicable washout period as defined by in section 8.8 'Prior and Concomitant Medication' and for the duration of the trial. Such participants will be potentially eligible at screening and will be confirmed as eligible if adequate washout is confirmed at visit
- •Participants currently participating in another interventional clinical trial.
Arms & Interventions
crisaborole and topical Corticosteroid
crisaborole (2%) ointment on the other forearm, twice daily application for 4 weeks (randomised site allocation) betamethasone valerate (0.1%) cream on one forearm, twice daily application for 4 weeks (randomised site allocation)
Intervention: crisaborole (2%) ointment
crisaborole and topical Corticosteroid
crisaborole (2%) ointment on the other forearm, twice daily application for 4 weeks (randomised site allocation) betamethasone valerate (0.1%) cream on one forearm, twice daily application for 4 weeks (randomised site allocation)
Intervention: betamethasone valerate 0.1% cream
Outcomes
Primary Outcomes
Change in Epidermal Thickness
Time Frame: Day 1 - Day 57
The difference in the change in epidermal thickness, measured by structural OCT, between the sites treated with crisaborole (2%) ointment and betamethasone valerate (0.1%) cream.
Secondary Outcomes
- Analysis of Change in Objective Erythema(Day 1, Day 15, Day 29 and Day 57)
- TEWL - Skin Barrier Function(Day 1, Day 15, Day 29 and Day 57)
- TEWL - After Tape-stripping(on Day 29, after 28 days treatment)
- Comparison of TEWL - After Tape-stripping(on Day 29, after 28 days treatment)
- Skin Dryness(Visual skin dryness scored on day 1, day 15, day 29 and day 57)
- Natural Moisturising Factor (NMF)(Day 29)
- Comparison of Natural Moisturising Factor (NMF) Between Treatments(Day 29)
- Change in Visual Redness/Erythema During and After 28 Days Treatment(Visual skin redness scored on day 1, day 15, day 29 and day 57)