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

Primary Purpose

Atopic Dermatitis, AD, Eczema

Status
Unknown status
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Dupilumab Only Product
Sponsored by
Eric Simpson
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Atopic Dermatitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    dupilumab

    Arm Description

    Outcomes

    Primary Outcome Measures

    Mean change from baseline in nerve length at week 24 in patients with AD
    Measured using confocal microscopy.

    Secondary Outcome Measures

    Mean change from baseline in dermal and epidermal nerve branching at week 24 for patients with AD
    Measured using confocal microscopy.
    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.
    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.
    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.
    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..
    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..
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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).
    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.
    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".
    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).
    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.
    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).
    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.
    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.

    Full Information

    First Posted
    July 24, 2020
    Last Updated
    August 18, 2020
    Sponsor
    Eric Simpson
    Collaborators
    Regeneron Pharmaceuticals
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04520308
    Brief Title
    An Open-label, Single-arm Longitudinal Study With Dupilumab for Patients With Atopic Dermatitis
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2020
    Overall Recruitment Status
    Unknown status
    Study Start Date
    September 1, 2020 (Anticipated)
    Primary Completion Date
    February 26, 2021 (Anticipated)
    Study Completion Date
    March 31, 2021 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Eric Simpson
    Collaborators
    Regeneron Pharmaceuticals

    4. Oversight

    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
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Atopic Dermatitis, AD, Eczema

    7. Study Design

    Primary Purpose
    Diagnostic
    Study Phase
    Phase 4
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    45 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    dupilumab
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Dupilumab Only Product
    Other Intervention Name(s)
    dupixent
    Intervention Description
    SC injections of 300 mg dupilumab every 2 weeks for 24 weeks following a loading dose of 600 mg on day 1
    Primary Outcome Measure Information:
    Title
    Mean change from baseline in nerve length at week 24 in patients with AD
    Description
    Measured using confocal microscopy.
    Time Frame
    24 weeks
    Secondary Outcome Measure Information:
    Title
    Mean change from baseline in dermal and epidermal nerve branching at week 24 for patients with AD
    Description
    Measured using confocal microscopy.
    Time Frame
    24 weeks
    Title
    Mean change from baseline in nerve substance P expression at week 24 for patients with AD
    Description
    Tissue whole mounts will be used to quantify neuronal expression of substance P.
    Time Frame
    24 weeks
    Title
    Mean change from baseline in nerve thymic stromal lymphopoietin (TSLP) receptor and IL-31 receptor expression at week 24 for patients with AD
    Description
    Tissue whole mounts will be used to quantify neuronal expression of TSLP.
    Time Frame
    24 weeks
    Title
    Mean change from baseline in nerve IL-4 receptor alpha (IL-4Rα) expression at week 24 for patients with AD
    Description
    Tissue whole mounts will be used to quantify neuronal expression of IL-31R and IL-4Rα.
    Time Frame
    24 weeks
    Title
    Mean change from baseline in keratinocyte TSLP expression at week 24 for patients with AD
    Description
    Tissue whole mounts will be used to quantify keratinocyte TSLP expression via microscopic examination..
    Time Frame
    24 weeks
    Title
    Mean change from baseline in eosinophil number and proximity to cutaneous nerves at week 24 for patients with AD
    Description
    Tissue whole mounts will be used to quantify eosinophil number and proximity to nerves via microscopic examination..
    Time Frame
    24 weeks
    Title
    Mean change from baseline in extracellular eosinophil peroxidase (EPX) staining at week 24 for patients with AD
    Description
    Tissue whole mounts will be used to quantify EPX staining via microscopic examination.
    Time Frame
    24 weeks
    Title
    Difference between normal control patients and patients with AD at baseline in mean dermal nerve branching
    Description
    Measured using confocal microscopy. Control patients will be compared with AD patients.
    Time Frame
    24 weeks
    Title
    Difference between normal control patients and patients with AD at baseline in mean nerve substance P expression
    Description
    Tissue whole mounts will be used to quantify neuronal expression of substance P. Control patients will be compared with AD patients.
    Time Frame
    24 weeks
    Title
    Difference between normal control patients and patients with AD at baseline in mean nerve TSLP receptor and IL-31 receptor expression
    Description
    Tissue whole mounts will be used to quantify neuronal expression of TSLP and IL-31R. Control patients will be compared with AD patients.
    Time Frame
    24 weeks
    Title
    Difference between normal control patients and patients with AD at baseline in mean nerve IL-4Rα expression
    Description
    Tissue whole mounts will be used to quantify neuronal expression of IL-4Rα via microscopic examination. Control patients will be compared with AD patients.
    Time Frame
    24 weeks
    Title
    Difference between normal control patients and patients with AD at baseline in mean keratinocyte TSLP expression
    Description
    Tissue whole mounts will be used to quantify keratinocyte TSLP expression via microscopic examination. Control patients will be compared with AD patients.
    Time Frame
    24 weeks
    Title
    Difference between normal control patients and patients with AD at baseline in mean eosinophil number and proximity to cutaneous nerves
    Description
    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.
    Time Frame
    24 weeks
    Title
    Difference between normal control patients and patients with AD at baseline in mean extracellular EPX staining
    Description
    Tissue whole mounts will be used to quantify EPX staining via microscopic examination. Control patients will be compared with AD patients.
    Time Frame
    24 weeks
    Title
    Mean change from baseline scores in pruritus numeric rating scale (NRS) at week 24 for patients with AD
    Description
    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.
    Time Frame
    24 weeks
    Title
    Mean change from baseline in patient global assessment (PGA) at week 24 for patients with AD
    Description
    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.
    Time Frame
    24 weeks
    Title
    Mean change from baseline in investigator's global assessment (IGA) at week 24 for patients with AD
    Description
    Investigators will rate the severity of AD globally, based on a 5 point scale ranging from 0 (clear) to 4 (severe).
    Time Frame
    24 weeks
    Title
    Mean change from baseline in Eczema Area and Severity Index (EASI) at week 24 for patients with AD
    Description
    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.
    Time Frame
    24 weeks
    Title
    Mean change from baseline in Skindex-3 scale ratings at week 24 for patients with AD
    Description
    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".
    Time Frame
    24 weeks
    Title
    Mean change from baseline in Sensitive Scale-10 at week 24 for patients with AD
    Description
    Patients will self-report degree and severity of overall skin irritation on a scale of 1-10 (0 = absence of irritation, 10 = intolerable irritation).
    Time Frame
    24 weeks
    Title
    Mean change from baseline in non-lesional skin sensitivity (stinger assay, measured with skin symptom scale) at week 24 for patients with AD
    Description
    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.
    Time Frame
    24 weeks
    Title
    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
    Description
    Trans-Epidermic Water Loss of lesional and non-lesional skin will also be assessed using non-invasive skin probe (g/h·m2).
    Time Frame
    24 weeks
    Title
    Mean change from baseline in lesional and non-lesional skin hydration scores (corneometry, measured in units) at week 24 for patients with AD
    Description
    Hydration of lesional and non-lesional skin will be assessed via non-invasive probes.
    Time Frame
    24 weeks
    Title
    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.
    Description
    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.
    Time Frame
    24 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Cody Blankenship
    Phone
    503-494-0171
    Email
    blankeco@ohsu.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Lindsay Chandler
    Phone
    503-494-2316
    Email
    chandlli@ohsu.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Eric Simspon, MD
    Organizational Affiliation
    Oregon Health and Science University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

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

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