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

• dupilumab (Drug), also known as Dupixent®, R668, SAR231893: Administered by subcutaneous (SC) injection once every 2 weeks (Q2W) following a loading dose
• Topical emollient (moisturizer) (Other): Moisturizer should be applied twice daily, as per physician's recommendation, as defined in protocol.

Primary outcomes

• Percentage of Participants With ≥75% Reduction From Baseline in Eczema Area and Severity Index (EASI) Score (EASI-75) [Week 24]: The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 24.

Secondary outcomes

• Percentage of Participants With an Investigator's Global Assessment (IGA) Score 0 to 1 [Weeks 2, 4, 8, 12, 16, 20, and 24]: IGA is an assessment scale used to determine severity of atopic dermatitis (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. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). Percentage of participants with IGA "0" or "1" are reported at each visit.
• Percent Change From Baseline in EASI Score [Weeks 2, 4, 8, 12, 16, 20, and 24]: The Eczema Area and Severity Index (EASI) score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.
• Change From Baseline in EASI Score [Weeks 2, 4, 8, 12, 16, 20, and 24]: The Eczema Area and Severity Index (EASI) score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.
• Percentage of Participants With ≥50% Reduction From Baseline in EASI Score (EASI-50) [Weeks 2, 4, 8, 12, 16, 20, and 24]: The EASI score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score from baseline to the given time point.
• Percentage of Participants With ≥75% Reduction From Baseline in EASI Score (EASI-75) [Weeks 2, 4, 8, 12, 16, 20, and 24]: The EASI score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to the given time point.
• Percentage of Participants With ≥90% Reduction From Baseline in EASI Score (EASI-90) [Weeks 2, 4, 8, 12, 16, 20, and 24]: The EASI score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-90 responders were the participants who achieved ≥90% overall improvement in EASI score from baseline to the given time point.
• Percent Change From Baseline in Total Scoring Atopic Dermatitis (SCORAD) Score [Weeks 2, 4, 8, 12, 16, 20, and 24]: The 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).
• Percentage of Participants With ≥50% Reduction From Baseline in SCORAD Score (SCORAD-50) [Weeks 2, 4, 8, 12, 16, 20, and 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.) were assessed and scored. Total score ranged from 0 (absent disease) to 103 (severe disease). A decrease in score indicated improvement. SCORAD-50 was defined as ≥50% reduction from baseline in SCORAD score.
• Percentage of Participants With Improvement (Reduction) From Baseline of Weekly Average of Daily Peak Pruritus (PP) Numerical Rating Scale (NRS) Score ≥3 [Weeks 2, 4, 8, 12, 16, 20, and 24]: Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. A decrease in score indicated improvement.
• Percentage of Participants With Improvement (Reduction) From Baseline of Weekly Average of Daily PP NRS Score ≥4 [Weeks 2, 4, 8, 12, 16, 20, and 24]: Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. A decrease in score indicated improvement.
• Percent Change From Baseline in Weekly Average of Daily PP NRS Score [Weeks 2, 4, 8, 12, 16, 20, and 24]: Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. A decrease in score indicated improvement.
• Change From Baseline in Weekly Average of Daily PP NRS Score [Weeks 2, 4, 8, 12, 16, 20, and 24]: Peak Pruritus NRS is an assessment tool used by subjects to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. A decrease in score indicated improvement.
• Percent Change From Baseline in Percent Body Surface Area (BSA) [Weeks 2, 4, 8, 12, 16, 20, and 24]: BSA affected by AD was assessed for each section of the body using the rule of nines (the possible highest score for each region was: head and neck \[9%\], interior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]). BSA was 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) Score [Weeks 2, 4, 8, 12, 16, 20, and 24]: DLQI is a 10-item, validated questionnaire to assess the impact of AD disease symptoms and treatment on QOL; over the past week, with an overall scoring of 0 (no effect on QoL) to 30 (extremely large effect on QoL). A decrease in score indicated improvement.
• Change From Baseline in Health-related QOL as Measured by Children's Dermatology Life Quality Index (CDLQI; Age <16) Score [Weeks 2, 4, 8, 12, 16, 20, and 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 (no effect on QoL) to 30 (extremely large effect on QoL) in children. A decrease in score indicated improvement.
• Change From Baseline in Patient Oriented Eczema Measure (POEM) Total Score [Weeks 2, 4, 8, 12, 16, 20, and 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) (Higher score indicative of more severe symptoms). Total score was an average of the disease symptoms assessed. A decrease in score indicated improvement.
• Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score [Weeks 2, 4, 8, 12, 16, 20, and 24]: The Hospital Anxiety and Depression Scale (HADS) is a screening tool designed to assess anxiety and depression. The scale consists of 14 items, divided into two subscales: Anxiety (HADS-A): 7 items; Depression (HADS-D): 7 items. The range of the total score is 0-42 (sum of HADS-A and HADS-D), with higher score indicating more severe overall psychological distress. The two subscales can be reported separately, each with a score range of 0-21, with higher score indicating more severe symptoms of anxiety or depression. A decrease in either the total score or a subscale score indicates improvement.
• Change From Baseline in Skin Pain NRS (SP NRS) Score [Weeks 2, 4, 8, 12, 16, 20, and 24]: SP NRS Scale is an assessment tool used to report the intensity of a participant's pain. Participants selected the number between 0 and 10 that fit best to their worst pain intensity over the past 24 hours (0 = no pain and 10 = the worst pain imaginable). A decrease in score indicated improvement.
• Change From Baseline in Weekly Average Sleep Quality NRS Score [Weeks 2, 4, 8, 12, 16, 20, and 24]: Sleep Quality NRS is an 11-point scale (0 to 10) in which 0 indicated worst possible sleep while 10 indicated best possible sleep. An increase in score indicated improvement.
• Percentage of Participants With Patient Global Impression of Disease (PGID) Response as No Symptoms [Weeks 2, 4, 8, 12, 16, 20, and 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. Data are reported for the percentage of participants with a PGID response of "No symptoms" at the specified timepoints.
• Percentage of Participants With PGID Response as No Symptoms or Mild Symptoms [Weeks 2, 4, 8, 12, 16, 20, and 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. Data are reported for the percentage of participants with a PGID response of "No symptoms" or "Mild symptoms" at the specified timepoints.
• Percentage of Participants Who Rated Their Eczema Symptoms in the Patient Global Impression of Change (PGIC) as "Much Better" [Weeks 2, 4, 8, 12, 16, 20, and 24]: The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change in eczema symptoms since starting treatment as rated on a 7-point Likert scale anchored by (1) "much better" to (7) "much worse", with (4) = "no change". Data are reported for the percentage of participants who rated their eczema symptoms as "Much better" at the specified timepoints.
• Percentage of Participants Who Rated Their Eczema Symptoms in the PGIC as "Moderately Better" [Weeks 2, 4, 8, 12, 16, 20, and 24]: The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change in eczema symptoms since starting treatment as rated on a 7-point Likert scale anchored by (1) "much better" to (7) "much worse", with (4) = "no change". Data are reported for the percentage of participants who rated their eczema symptoms as "Moderately better" at the specified timepoints.
• Number of Participants With Non-herpetic Skin Infection Treatment-emergent Adverse Events (TEAEs) [Day 1 through Week 24]: A TEAE is any untoward medical occurrence in a participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. Data are reported for the number of participants with non-herpetic skin infection TEAEs. A summary of all serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
• Change From Baseline in Total Immunoglobulin (E) IgE [Weeks 4, 12 and 24]: Serum samples were collected to measure concentrations of IgE.
• Percent Change From Baseline in Total IgE [Weeks 4, 12 and 24]: Serum samples were collected to measure concentrations of IgE.
• Trough Concentration of Functional Dupilumab in Serum [Week 12 and Week 24]: Adolescents and adults received 1 of 2 dose regimens based on age and body weight. The trough concentration of functional dupilumab in serum for the 2 dose regimens at the specified time points are presented. Participants treated and had at least one evaluable post-first-dose concentration measurement.

Sex: All, ages: 12 Years to any

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

Participant flow

Outcome results

• Percentage of Participants With an Investigator's Global Assessment (IGA) Score 0 to 1 (Secondary), Number, percentage of participants: Dupilumab 0.9
• Percent Change From Baseline in EASI Score (Secondary), Mean, percent change: Dupilumab -25.929 +/- 29.782
• Change From Baseline in EASI Score (Secondary), Mean, score on scale: Dupilumab -7.105 +/- 7.504
• Percentage of Participants With ≥50% Reduction From Baseline in EASI Score (EASI-50) (Secondary), Number, percentage of participants: Dupilumab 17.2
• Percentage of Participants With ≥75% Reduction From Baseline in EASI Score (EASI-75) (Secondary), Number, percentage of participants: Dupilumab 3.4
• Percentage of Participants With ≥90% Reduction From Baseline in EASI Score (EASI-90) (Secondary), Number, percentage of participants: Dupilumab 0.9
• Percent Change From Baseline in Total Scoring Atopic Dermatitis (SCORAD) Score (Secondary), Mean, percent change: Dupilumab -18.5 +/- 17.8
• Percentage of Participants With ≥50% Reduction From Baseline in SCORAD Score (SCORAD-50) (Secondary), Number, percentage of participants: Dupilumab 9.1
• Percentage of Participants With Improvement (Reduction) From Baseline of Weekly Average of Daily Peak Pruritus (PP) Numerical Rating Scale (NRS) Score ≥3 (Secondary), Number, percentage of participants: Dupilumab 14.3
• Percentage of Participants With Improvement (Reduction) From Baseline of Weekly Average of Daily PP NRS Score ≥4 (Secondary), Number, percentage of participants: Dupilumab 8.4
• Percent Change From Baseline in Weekly Average of Daily PP NRS Score (Secondary), Mean, Percentage of change: Dupilumab -16.253 +/- 25.364
• Change From Baseline in Weekly Average of Daily PP NRS Score (Secondary), Mean, score on a scale: Dupilumab -1.234 +/- 1.663
• Percent Change From Baseline in Percent Body Surface Area (BSA) (Secondary), Mean, Percentage of change: Dupilumab -17.91 +/- 24.92
• Change From Baseline in Health-related Quality of Life (QOL) as Measured by Dermatology Life Quality Index (DLQI; Age ≥16) Score (Secondary), Mean, score on a scale: Dupilumab -4.5 +/- 5.4
• Change From Baseline in Health-related QOL as Measured by Children's Dermatology Life Quality Index (CDLQI; Age <16) Score (Secondary), Mean, score on a scale: Dupilumab -4.2 +/- 5.4
• Change From Baseline in Patient Oriented Eczema Measure (POEM) Total Score (Secondary), Mean, score on a scale: Dupilumab -5.6 +/- 6.0
• Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score (Secondary), Mean, score on a scale: Dupilumab -1.8 +/- 5.0
• Change From Baseline in Skin Pain NRS (SP NRS) Score (Secondary), Mean, score on a scale: Dupilumab -2.3 +/- 3.6
• Change From Baseline in Weekly Average Sleep Quality NRS Score (Secondary), Mean, score on a scale: Dupilumab 0.473 +/- 1.565
• Percentage of Participants With Patient Global Impression of Disease (PGID) Response as No Symptoms (Secondary), Number, percentage of participants: Dupilumab 4.0
• 8 more outcome measures not shown.

Adverse events

Time frame: Day 1 through Week 24

Serious adverse events by term

• Study Protocol (PDF, 2024-04-02)
• Statistical Analysis Plan (PDF, 2024-12-06)

• Clinical Trial Management, Study director, Regeneron Pharmaceuticals