An Open-label, Single-arm Longitudinal Study With Dupilumab for Patients With Atopic Dermatitis

Effects of Interleukin (IL)-4/IL-13 Blockade on the Structure and Function of Cutaneous Sensory Nerves: An Open-label, Single-arm Longitudinal Study With Dupilumab

24-week, open-label, single-arm longitudinal study of patients with AD, including a comparison between baseline values for adult patients with moderate-to-severe AD and untreated normal control patients.

Patients with AD: ≤24 to 29 weeks, including the screening period Normal control patients: ≤2 days to 5 weeks, including the screening period.

Patients with AD: adults with moderate-to-severe AD whose disease cannot be adequately controlled with topical medications or for whom topical treatment is medically inadvisable (eg, intolerance, other important side effects or safety risks)

Normal control patients: adults without AD or other atopic disease

Study Overview

• Status: Unknown
• Conditions: Eczema; Atopic Dermatitis; AD
• Intervention / Treatment: Drug: Dupilumab Only Product

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Cody Blankenship; Phone Number: 503-494-0171; Email: blankeco@ohsu.edu
• Study Contact Backup: Name: Lindsay Chandler; Phone Number: 503-494-2316; Email: chandlli@ohsu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All patients:

• Male or female, 18 years or older
• Willing and able to comply with clinic visits and study-related procedures
• Provide signed informed consent
• Have applied a stable dose of topical emollient (moisturizer) once daily for at least 7 days before the day 1 visit

AD patients only:

• Chronic AD
• Eczema Area and Severity Index (EASI) ≥16 at screening and day 1 visits
• Investigator's global assessment (IGA) ≥3 (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) at the screening and day 1 visits
• Body surface area of involvement of AD (BSA) ≥10% at screening and day 1 visits
• Documented recent history (within 6 months before screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable

Exclusion Criteria for all patients (not all inclusive):

• Prior use of dupilumab or other anti-IL-4 treatments (prescription or as part of a clinical study) within 1 year of screening
• Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known) before the day 1 visit, whichever is longer
• Having used immunosuppressive drugs or phototherapy within the last 4 weeks
• Treatment with TCS or TCI within 1 week before the day 1 visit
• Regular use (>2 visits/week) of a tanning booth/parlor within 4 weeks before the screening visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dupilumab	Drug: Dupilumab Only Product; SC injections of 300 mg dupilumab every 2 weeks for 24 weeks following a loading dose of 600 mg on day 1; Other Names: dupixent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in nerve length at week 24 in patients with AD	Measured using confocal microscopy.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in dermal and epidermal nerve branching at week 24 for patients with AD	Measured using confocal microscopy.	24 weeks
Mean change from baseline in nerve substance P expression at week 24 for patients with AD	Tissue whole mounts will be used to quantify neuronal expression of substance P.	24 weeks
Mean change from baseline in nerve thymic stromal lymphopoietin (TSLP) receptor and IL-31 receptor expression at week 24 for patients with AD	Tissue whole mounts will be used to quantify neuronal expression of TSLP.	24 weeks
Mean change from baseline in nerve IL-4 receptor alpha (IL-4Rα) expression at week 24 for patients with AD	Tissue whole mounts will be used to quantify neuronal expression of IL-31R and IL-4Rα.	24 weeks
Mean change from baseline in keratinocyte TSLP expression at week 24 for patients with AD	Tissue whole mounts will be used to quantify keratinocyte TSLP expression via microscopic examination..	24 weeks
Mean change from baseline in eosinophil number and proximity to cutaneous nerves at week 24 for patients with AD	Tissue whole mounts will be used to quantify eosinophil number and proximity to nerves via microscopic examination..	24 weeks
Mean change from baseline in extracellular eosinophil peroxidase (EPX) staining at week 24 for patients with AD	Tissue whole mounts will be used to quantify EPX staining via microscopic examination.	24 weeks
Difference between normal control patients and patients with AD at baseline in mean dermal nerve branching	Measured using confocal microscopy. Control patients will be compared with AD patients.	24 weeks
Difference between normal control patients and patients with AD at baseline in mean nerve substance P expression	Tissue whole mounts will be used to quantify neuronal expression of substance P. Control patients will be compared with AD patients.	24 weeks
Difference between normal control patients and patients with AD at baseline in mean nerve TSLP receptor and IL-31 receptor expression	Tissue whole mounts will be used to quantify neuronal expression of TSLP and IL-31R. Control patients will be compared with AD patients.	24 weeks
Difference between normal control patients and patients with AD at baseline in mean nerve IL-4Rα expression	Tissue whole mounts will be used to quantify neuronal expression of IL-4Rα via microscopic examination. Control patients will be compared with AD patients.	24 weeks
Difference between normal control patients and patients with AD at baseline in mean keratinocyte TSLP expression	Tissue whole mounts will be used to quantify keratinocyte TSLP expression via microscopic examination. Control patients will be compared with AD patients.	24 weeks
Difference between normal control patients and patients with AD at baseline in mean eosinophil number and proximity to cutaneous nerves	Tissue whole mounts will be used to quantify eosinophil number and proximity to nerves via microscopic examination. Control patients will be compared with AD patients.	24 weeks
Difference between normal control patients and patients with AD at baseline in mean extracellular EPX staining	Tissue whole mounts will be used to quantify EPX staining via microscopic examination. Control patients will be compared with AD patients.	24 weeks
Mean change from baseline scores in pruritus numeric rating scale (NRS) at week 24 for patients with AD	Patients will report the intensity of their pruritus using the pruritus numeric scale (NRS), a 0-10 scale (0 being 'no itch' and 10 being the 'worst itch imaginable'). This scale captures rate of itch overall (average itch intensity) during the previous 24 hours and rate of itch at the worst moment (maximum itch intensity) during the previous 24 hours.	24 weeks
Mean change from baseline in patient global assessment (PGA) at week 24 for patients with AD	Patients will rate their overall well-being (poor, fair, good, very good, excellent) using the patient global assessment (PGA). Patients will also rate their atopic dermatitis/eczema as: clear, almost clear, mild, moderate, or severe.	24 weeks
Mean change from baseline in investigator's global assessment (IGA) at week 24 for patients with AD	Investigators will rate the severity of AD globally, based on a 5 point scale ranging from 0 (clear) to 4 (severe).	24 weeks
Mean change from baseline in Eczema Area and Severity Index (EASI) at week 24 for patients with AD	Investigators will assess the severity and extent of AD with the EASI composite index. Severity scores range from 0 to 72 for AD disease characteristics, which will be assessed by the investigator on a scale of "0" (absent) through "3" (severe). The area of AD involvement will be assessed as a percentage by body area and converted to a score of 0 to 6.	24 weeks
Mean change from baseline in Skindex-3 scale ratings at week 24 for patients with AD	The Skindex-3 is a 3-question quality of life assessment, which will assess patients' current state of activity (going out, work activities or relationships with others), emotion (worry, embarrassment, frustration), and skin symptoms (itching, stinging, burning, hurting or skin irritation). Each question is graded on a scale of 0 "never bothered" to 6 "always bothered".	24 weeks
Mean change from baseline in Sensitive Scale-10 at week 24 for patients with AD	Patients will self-report degree and severity of overall skin irritation on a scale of 1-10 (0 = absence of irritation, 10 = intolerable irritation).	24 weeks
Mean change from baseline in non-lesional skin sensitivity (stinger assay, measured with skin symptom scale) at week 24 for patients with AD	Non-lesional skin sensitivity will be assessed via the stinger assay using 5% lactic acid with patient-reported stinging. The scale of stinging skin symptoms will be used: 0 = none; 1 = slight; 2 = moderate; and 3 = severe.	24 weeks
Mean change from baseline in lesional and non-lesional skin hydration (Trans-Epidermic Water Loss, measured in g/h·m2) at week 24 for patients with AD	Trans-Epidermic Water Loss of lesional and non-lesional skin will also be assessed using non-invasive skin probe (g/h·m2).	24 weeks
Mean change from baseline in lesional and non-lesional skin hydration scores (corneometry, measured in units) at week 24 for patients with AD	Hydration of lesional and non-lesional skin will be assessed via non-invasive probes.	24 weeks
Mean change from baseline scores in lesional and non-lesional at-home skin barrier testing (measuring skin hydration by Trans-Epidermic Water Loss and Stratum Corneum Hydration, assessed in units) using a GP device at 24 weeks for patients with AD.	Lesional and non-lesional skin hydration (Trans-Epidermic Water Loss and Stratum Corneum Hydration, assessed in units) by patients using an at-home GP skin barrier device.	24 weeks

Collaborators and Investigators

• Sponsor: Eric Simpson
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Principal Investigator: Eric Simspon, MD, Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): February 26, 2021
• Study Completion (Anticipated): March 31, 2021

Study Registration Dates

• First Submitted: July 24, 2020
• First Submitted That Met QC Criteria: August 18, 2020
• First Posted (Actual): August 20, 2020

Study Record Updates

• Last Update Posted (Actual): August 20, 2020
• Last Update Submitted That Met QC Criteria: August 18, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: STUDY00021061

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes