DISCOVER: Dupilumab In Adolescent and Adult Skin of Color Participants: Open-label Moderate-to-seVere Eczema tRial
Study Details
Study Description
Brief Summary
The primary objective of the study is:
• To describe further the efficacy of dupilumab on extent and severity of eczematous lesions in skin of color participants, at least (≥)12 years old, with moderate-to-severe atopic dermatitis (AD)
The secondary objectives of the study are:
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To describe further the efficacy of dupilumab on pruritus and other AD symptoms in skin of color participants, ≥12 years old, with moderate-to-severe AD
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To describe further the efficacy of dupilumab on measures of mental health (anxiety and depression) and quality of life (QOL) in skin of color participants, ≥12 years old, with moderate-to-severe AD
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To describe further the safety of dupilumab administered to skin of color participants, ≥12 years old, with moderate-to-severe AD
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To assess dupilumab modulation of type 2 biomarkers in skin of color participants, ≥12 years old, with moderate-to-severe AD
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To evaluate further the systemic exposure of dupilumab in skin of color participants, ≥12 years old, with moderate-to-severe AD
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: dupilumab Adolescents and adults will receive 1 of 2 dose regimens based on age and body weight |
Drug: dupilumab
Administered by subcutaneous (SC) injection once every 2 weeks (Q2W) following a loading dose
Other Names:
Other: Topical emollient (moisturizer)
Moisturizer should be applied twice daily, as per physician's recommendation, as defined in protocol.
|
Outcome Measures
Primary Outcome Measures
- Proportion of participants with eczema area and severity index (EASI)-75 [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.
Secondary Outcome Measures
- Proportion of participants with Investigator's Global Assessment (IGA) = 0 to 1 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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) [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) [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) [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) [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) [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) [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 [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 [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 [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" [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" [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) [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 [Baseline to Weeks 4, 12 and 24]
- Percent change in total and allergen-specific IgEs [Baseline to Weeks 4, 12 and 24]
- Trough concentration of functional dupilumab in serum [At Baseline, Week 12 and Week 24]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Skin of color, defined as Fitzpatrick skin type ≥4 at screening visit
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Diagnosis of moderate-to-severe atopic dermatitis (AD) that cannot be adequately controlled with topical AD medications, as defined in protocol
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Has applied a stable dose of topical emollient (moisturizer) twice daily as per physician recommendation starting at screening visit
Key Exclusion Criteria:
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Self-reported Caucasian or White race
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Adolescent body weight less than 30 kg at screening
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Prior use of dupilumab within 6 months of screening
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Concomitant skin diseases or other pigmentary disorder that could confound AD assessments
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Current or prior use, within 12 weeks before the screening visit, of phototherapy or tanning beds
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Active helminthic infections; suspected or high risk of helminthic infection, unless clinical and (if necessary) laboratory assessments have ruled out active infection before baseline
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Treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within 7 days prior to baseline
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Planned or anticipated use of any prohibited medications and procedures, as defined in protocol
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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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Regeneron Pharmaceuticals
- Sanofi
Investigators
- Study Director: Clinical Trial Management, Regeneron Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R668-AD-2217