Dupilumab in Adolescent and Adult Skin of Color Participants: Open-label Moderate-to-severe Eczema Trial (DISCOVER)

• ClinicalTrials.gov Identifier: NCT05590585
• Recruitment Status: Recruiting
• First Posted: October 21, 2022
• Last Update Posted: March 1, 2024
• Sponsor: Regeneron Pharmaceuticals
• Collaborator: Sanofi
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: October 18, 2022
• First Posted Date: October 21, 2022
• Last Update Posted Date: March 1, 2024
• Actual Study Start Date: January 11, 2023
• Estimated Primary Completion Date: July 23, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 18, 2022)

Proportion of participants with eczema area and severity index (EASI)-75 [ Time Frame: At Week 24 ]

EASI is a composite index measuring the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD. EASI-75 is ≥75% reduction from baseline in EASI.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 18, 2022)

• Proportion of participants with Investigator's Global Assessment (IGA) = 0 to 1 [ Time Frame: Each Visit, Baseline Through Week 24 ]
  IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration.
• Percent change from baseline in EASI [ Time Frame: Each Visit, Baseline Through Week 24 ]
  EASI is a composite index measuring the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD.
• Absolute change from baseline in EASI [ Time Frame: Each Visit, Baseline Through Week 24 ]
  EASI is a composite index measuring the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD.
• Proportion of participants with EASI-50 [ Time Frame: Each Visit, Baseline Through Week 24 ]
  EASI is a composite index measuring the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD. EASI-50 is ≥50% reduction from baseline in EASI
• Proportion of participants with EASI-75 [ Time Frame: Each Visit, Baseline Through Week 24 ]
  EASI is a composite index measuring the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD. EASI-75 is ≥75% reduction from baseline in EASI
• Proportion of participants with EASI-90 [ Time Frame: Each Visit, Baseline Through Week 24 ]
  EASI is a composite index measuring the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD. EASI-90 is ≥90% reduction from baseline in EASI
• Percent change from baseline in total SCORing atopic dermatitis (AD) (SCORAD) component scores [ Time Frame: Each Visit, Baseline Through Week 24 ]
  SCORAD index is a clinical tool for assessing the severity of atopic dermatitis. Extent and intensity of eczema as well as subjective signs insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).
• Proportion of participants with SCORAD-50 [ Time Frame: Each Visit, Baseline Through Week 24 ]
  SCORAD index is a clinical tool for assessing the severity of atopic dermatitis. Extent and intensity of eczema as well as subjective signs insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). SCORAD-50 is ≥50% reduction in SCORAD
• Proportion of participants with improvement (reduction) of weekly average of daily Peak Pruritus (PP) Numerical Rating Scale (NRS) ≥3 from baseline [ Time Frame: Each Visit, Baseline Through Week 24 ]
  Peak Pruritus NRS is a simple assessment tool that participants will use to report the average intensity of their pruritus (itch), both maximum and average intensity, during a 24-hour recall period; maximum itch intensity on a scale of 0 - 10 (0 = no itch; 10 = worst itch imaginable)
• Proportion of participants with improvement (reduction) of weekly average of daily PP NRS ≥4 [ Time Frame: Each Visit, Baseline Through Week 24 ]
  Peak Pruritus NRS is a simple assessment tool that participants will use to report the average intensity of their pruritus (itch), both maximum and average intensity, during a 24-hour recall period; maximum itch intensity on a scale of 0 - 10 (0 = no itch; 10 = worst itch imaginable)
• Percent change from baseline in weekly average of daily PP NRS [ Time Frame: Each Visit, Baseline Through Week 24 ]
  Peak Pruritus NRS is a simple assessment tool that participants will use to report the average intensity of their pruritus (itch), both maximum and average intensity, during a 24-hour recall period; maximum itch intensity on a scale of 0 - 10 (0 = no itch; 10 = worst itch imaginable)
• Absolute change from baseline in weekly average of daily PP NRS [ Time Frame: Each Visit, Baseline Through Week 24 ]
  Peak Pruritus NRS is a simple assessment tool that participants will use to report the average intensity of their pruritus (itch), both maximum and average intensity, during a 24-hour recall period; maximum itch intensity on a scale of 0 - 10 (0 = no itch; 10 = worst itch imaginable)
• Change from baseline in percent body surface area (BSA) [ Time Frame: Each Visit, Baseline Through Week 24 ]
  BSA affected by AD will be assessed for each section of the body using the rule of nines (the possible highest score for each region is: head and neck [9%], interior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]) and will be reported as a percentage of all major body sections combined.
• Change from baseline in health-related quality of life (QOL) as measured by Dermatology Life Quality Index (DLQI; age ≥16) [ Time Frame: Each Visit, Baseline Through Week 24 ]
  DLQI is a 10-item, validated questionnaire to assess the impact of AD disease symptoms and treatment on quality of life (QOL); over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score was indicative of a poor QOL.
• Change from baseline in health-related QOL as measured by Children's Dermatology Life Quality Index (CDLQI; age <16) [ Time Frame: Each Visit, Baseline Through Week 24 ]
  CDLQI is a 10-item, validated questionnaire to assess the impact of AD disease symptoms and treatment on quality of life (QOL); over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score was indicative of a poor QOL in children.
• Change from baseline in Patient Oriented Eczema Measure (POEM) [ Time Frame: Each Visit, Baseline Through Week 24 ]
  POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]).
• Change from baseline in Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Each Visit, Baseline Through Week 24 ]
  HADS is a 14-item questionnaire, (7)for anxiety and (7) for depression symptoms; possible scores range from 0 to 21 for each subscale. The following cut-off scores are recommended for both subscales: 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression.
• Change from baseline in Skin Pain NRS (SP NRS) [ Time Frame: Each Visit, From Baseline Through Week 24 ]
  SP NRS Scale is an assessment tool used to report the intensity of a patient's pain. Patients will select the number between 0 and 10 that fits best to their worst pain intensity over the past 24 hours (0 = no pain and 10 = the worst pain possible).
• Change from baseline in weekly average Sleep Quality NRS [ Time Frame: Each Visit, Baseline Through Week 24 ]
  Sleep Quality NRS is an 11-point scale (0 to 10) in which 0 indicates worst possible sleep while 10 indicates best possible sleep.
• Proportion of patient global impression of disease (PGID) response as No symptoms [ Time Frame: Each Visit, Through Week 24 ]
  PGID is a single 1-item questionnaire designed to assess participant's overall impression of disease severity during the past 7 days with a 5-level scale of no symptoms, mild, moderate, severe or very severe.
• Proportion of participants with PGID response as No symptoms or Mild symptoms [ Time Frame: Each Visit, Through Week 24 ]
  PGID is a single 1-item questionnaire designed to assess participant's overall impression of disease severity during the past 7 days with a 5-level scale of no symptoms, mild, moderate, severe or very severe.
• Proportion of participants who rate their eczema symptoms in the patient global impression of change (PGIC) as "Much better" [ Time Frame: Each Visit, Through Week 24 ]
  The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 5-point Likert scale anchored by (1) "much better" to (5) "much worse", with (4) = "no change"
• Proportion of participants who rate their eczema symptoms in PGIC as "Much better" or "Moderately better" [ Time Frame: Each Visit, Through Week 24 ]
  The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 5-point Likert scale anchored by (1) "much better" to (5) "much worse", with (4) = "no change"
• Incidence of non-herpetic skin infection treatment-emergent adverse events (TEAEs) [ Time Frame: Through Last Study Visit, at Week 24 ]
  TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
• Change in total and allergen-specific immunoglobulin (E) IgEs [ Time Frame: Baseline to Weeks 4, 12 and 24 ]
• Percent change in total and allergen-specific IgEs [ Time Frame: Baseline to Weeks 4, 12 and 24 ]
• Trough concentration of functional dupilumab in serum [ Time Frame: At Baseline, Week 12 and Week 24 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dupilumab in Adolescent and Adult Skin of Color Participants: Open-label Moderate-to-severe Eczema Trial
• Official Title: An Open-Label Single-Arm Study of Dupilumab in Adolescent and Adult Skin of Color Patients With Moderate-to-Severe Atopic Dermatitis

Brief Summary

The study is focused on skin of color participants who have moderate-to-severe atopic dermatitis. Atopic dermatitis, also referred to as eczema, is a condition that causes the skin to become itchy, dry, and cracked.

From the previous studies on the study drug, it is seen that the study drug has an acceptable safety and effectiveness in participants with atopic dermatitis.

The aim of this study is to get additional information on the safety and effectiveness of the study drug, particularly the information on aspects of atopic dermatitis in skin of color participants.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drug
• How much study drug is in your blood at different times
• How much the study drug improves quality of life and mental health

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Moderate-to-Severe Atopic Dermatitis
• Atopic Eczema

Intervention

• Drug: dupilumab
  Administered by subcutaneous (SC) injection once every 2 weeks (Q2W) following a loading dose
  Other Names:

  • Dupixent®
  • R668
  • SAR231893
• Other: Topical emollient (moisturizer)
  Moisturizer should be applied twice daily, as per physician's recommendation, as defined in protocol.

Study Arms

Experimental: dupilumab

Adolescents and adults will receive 1 of 2 dose regimens based on age and body weight

Interventions:

• Drug: dupilumab
• Other: Topical emollient (moisturizer)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 18, 2022): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 23, 2025
• Estimated Primary Completion Date: July 23, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. Skin of color, defined as Fitzpatrick skin type ≥4 at screening visit
2. Diagnosis of moderate-to-severe atopic dermatitis (AD) that cannot be adequately controlled with topical AD medications, as defined in protocol
3. Has applied a stable dose of topical emollient (moisturizer) twice daily as per physician recommendation starting at screening visit

Key Exclusion Criteria:

1. Self-reported Caucasian or White race
2. Adolescent body weight less than 30 kg at screening
3. Prior use of dupilumab within 6 months of screening
4. Concomitant skin diseases or other pigmentary disorder that could confound AD assessments
5. Current or prior use, within 12 weeks before the screening visit, of phototherapy or tanning beds
6. Active helminthic infections; suspected or high risk of helminthic infection, unless clinical and (if necessary) laboratory assessments have ruled out active infection before baseline
7. Treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within 7 days prior to baseline
8. Planned or anticipated use of any prohibited medications and procedures, as defined in protocol
9. Has received a COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study drug

NOTE: Other Protocol Defined Inclusion / Exclusion Criteria Apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05590585
• Other Study ID Numbers: R668-AD-2217
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• URL: https://vivli.org/

• Current Responsible Party: Regeneron Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Regeneron Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Sanofi

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: January 2024