Atopic Dermatitis MedDRA version: 20.0 Level: PT Classification code 10012438 Term: Dermatitis atopic System Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Conditions
Interventions
Product Name: Dupilumab
Product Code: SAR231893
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Dupilumab
Current Sponsor code: SAR231893
Other descriptive name:
Sponsors
Sanofi-aventis Recherche & Développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For Atopic dermatitis patients Male or female of =18 years of age inclusive, at the time of signing the informed consent form (ICF). Diagnosed with moderate-to-severe chronic AD for at least 1 year before screening. Eligible to be treated with dupilumab according to product monograph. Pruritus lasting 6 or more weeks before baseline (Day 1). Eczema Area and Severity Index (EASI) score =12 at baseline. Pruritus numerical rating scale (NRS) =4 at baseline. Investigator global assessment (IGA) score of =3 at screening (on the 0 to 4 scale) at baseline. Atopic dermatitis active lesions on the upper limbs or lower limbs suitable for a skin biopsy without oozing, bleeding, or infection on upper limbs or trunk. Patients with acute AD lesions as determined by Investigator’s judgment. Stable treatment with non-prohibited medication or therapy during the study. For Healthy participants Male or female of =18 years of age inclusive, at the time of signing the ICF. Certified as generally healthy by a comprehensive clinical assessment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: For atopic dermatitis patients Previous treatment with dupilumab stopped within 6 months of baseline due to inadequate response to dupilumab. Skin conditions other than AD that can confound assessments in the opinion of theinvestigator. Regular use (>2 visits per week) of a tanning booth/parlor within 4 weeks of the Screening Visit. Severe concomitant illness(es) that, in the Investigator’s judgment, would adversely affect the patient’s participation in the study. Patients with active tuberculosis (TB) or non-TB mycobacterial infection, or a history of incompletely treated TB unless it is well documented the participant has been adequately treated and can now start treatment with a biologic agent Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drug within 2 weeks before the Screening Visit (Visit 1) or during the Screening Period. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals,or antifungals within 2 weeks before the Screening Visit (Visit 1) or during the Screening Period. Known or suspected immunodeficiency, including history of invasive opportunistic infections Active malignancy or history of malignancy within 5 years before the Baseline Visit, except completely treated in situ carcinoma of the cervix and completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin. Ocular disorder that in the opinion of the Investigator could adversely affect the individual’s risk for study participation. Examples include, but are not limited to,individuals with a history of active cases of herpes keratitis, Sjogren’s syndrome, keratoconjunctivitis sicca or dry eye syndrome that require daily use of supplemental lubrication or individuals with ocular conditions that require the use of ocular corticosteroids or cyclosporine. History of systemic hypersensitivity or anaphylaxis to dupilumab or any other biologic therapy, including any excipient. Participant with any other medical or psychological condition including relevant laboratory or electrocardiogram abnormalities at screening For healthy participants Regular use (>2 visits per week) of a tanning booth/ parlor within 4 weeks of the Screening Visit Treatment with the following concomitant medications and procedures is prohibited within 4 weeks before the Screening Visit or 5 half-lives (whichever is longer) until EoS Visit:- Topical medication. Analgesics. Immunomodulators. Antidepressants. Anti-anxiety drugs. Any Type 2 immune disorders uncontrolled Type 2 diabetes mellitus, Type 1 diabetes mellitus, neuropathy or any other neurological disease. Any concomitant illness(es) or conditions that, in the Investigator’s judgment, would adversely affect the subject’s participation in the study or potentially affect any skin biopsy related read out. Positive test for immunoglobulin E (IgE) antibodies.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: - Assess change in neuronal architecture following short term treatment with dupilumab and during follow-up in skin biopsies from AD participants with chronic pruritus - To evaluate the efficacy of dupilumab in AD participants with chronic puritus - To evaluate the safety of dupilumab in adult participants with moderate-to-severe AD ;Primary end point(s): 1 - Change from baseline in intraepidermal nerve fiber density ; Quantification of intraepidermal nerve fiber density will be calculated by assessing nerve fibers crossing the basement membrane per square millimetre (F/mm2) 2 - Change from baseline in nerve fiber branching ; Branching of nerve fibers will be assessed semi-quantitatively by classifying patients into 4 groups comprised of only linear, mainly linear, mainly branched or only branched fibers.;Main Objective: Assess change in neuronal architecture following long term treatment with dupilumab in skin biopsies from atopic dermatitis (AD) participants with chronic pruritus ;Timepoint(s) of evaluation of this end point: 1, 2 - baseline to week 17 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - Change from baseline in intraepidermal nerve fiber density ; Quantification of intraepidermal nerve fiber density will be calculated by assessing nerve fibers crossing the basement membrane per square millimetre (F/mm2) 2 - Change from baseline in nerve fiber branching ; Branching of nerve fibers will be assessed semi-quantitatively by classifying patients into 4 groups comprised of only linear, mainly linear, mainly branched or only branched fibers. 3 - Change from baseline in the outcome of peak pruritus assessed by numeric rating scale (NRS) ; The peak pruritus NRS is a simple assessment tool that participants = 12 to <18 years old will use to report the intensity of their pruritus (itch) ranges from 0 to 10 with 0 being 'no itch' and 10 being the' worst itch imaginable'' 4 - Change from baseline in the outcome of eczema and severity index (EASI) ; The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicates worse condition 5 - Change from baseline in the outcome of scoring atopic dermatitis (SCORAD ; SCORAD was used to assess the extent and severity of AD. Extent and severity of eczema as well as subjective assessment of symptoms were assessed and scored. SCORAD total score ranges from 0 (absent disease) to 103 (severe disease). 6 - Change from baseline in the outcome of Patient-Reported Outcomes Measurement Information (PROMIS-itch ; PROMIS-itch is an assessment of itch . The short form of following item will be used with no summary score. Itch-severity; activity and clothing; mood and sleep; interference; scratching behavior; quality; trigger. 7 - Change from baseline in the outcome of Patient Oriented Eczema Measure (POEM) ; POEM is a 7-item (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) questionnaire to assess frequency of disdase symptoms with a scoring system of 0 to 28. The higher score indicating higher severiy 8 - Change from baseline in the outcome of Patient Oriented | — |
Countries
Germany, United States
Outcome results
None listed