A Study to Assess the Efficacy and Safety of Dupilumab in Participants With Severe Atopic Dermatitis (AD) That Are Not Controlled With Oral Cyclosporine A (CSA) or for Those Who Cannot Take Oral CSA Because it is Not Medically Advisable

A Phase 3 Study Investigating the Efficacy, Safety, and Tolerability of Dupilumab Administered to Adult Patients With Severe Atopic Dermatitis Who Are Not Adequately Controlled With or Are Intolerant to Oral Cyclosporine A, or When This Treatment is Not Medically Advisable

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02755649

Enrollment

325

Registered

2016-04-29

Start date

2016-01-31

Completion date

2017-03-31

Last updated

2020-08-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Atopic Dermatitis

Brief summary

The main objective of the trial is to evaluate the efficacy of 2 dose regimens of dupilumab compared to placebo, administered with concomitant topical corticosteroids (TCS), in adult patients with severe AD who are not adequately controlled with, or are intolerant to, oral Cyclosporine A (CSA), or when this treatment is currently not medically advisable. The secondary objective is to assess the safety and tolerability of 2 dose regimens of dupilumab compared to placebo, administered with concomitant TCS, in adult patients with severe AD who are not adequately controlled with, or are intolerant to, oral CSA, or when this treatment is currently not medically advisable.

Interventions

DRUGDupilumab

DRUGMatching Placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Male or female, 18 years or older 2. Severe, Chronic AD, (according to American Academy of Dermatology Consensus Criteria \[Eichenfield 2014\]) for whom treatment with potent TCS is indicated 3. EASI score ≥20 at the screening and baseline visits 4. IGA score ≥3 (on the 0 to 4 IGA scale) at the screening and baseline visits 5. ≥10% body surface area (BSA) of AD involvement at the screening and baseline visits 6. Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with TCS 7. Have applied a stable dose of topical emollient (moisturizer) twice daily for at least the 7 consecutive days immediately before the baseline visit 8. Documented history by a physician of either: 1. No prior CSA exposure and not currently a candidate for CSA treatment due to: * medical contraindications (eg, uncontrolled hypertension on medication), or * use of prohibited concomitant medications (eg, statins, digoxin, macrolide, antibiotics, barbiturates, anti-seizure, nonsteroidal anti-inflammatory drugs, diuretics, angiotensin-converting-enzyme inhibitors, St John's Wort, etc), or * increased susceptibility to CSA-induced renal damage (elevated creatinine) and liver damage (elevated function tests), or * increased risk of serious infections, or * hypersensitivity to CSA active substance or excipients OR 2. Previously exposed to CSA, and CSA treatment should not be continued or restarted due to: * intolerance and/or unacceptable toxicity (eg, elevated creatinine, elevated liver function tests, uncontrolled hypertension, paraesthesia, headache, nausea, hypertrichosis, etc), or * inadequate response to CSA (defined as flare of AD on CSA tapering after a maximum of 6 weeks of high dose \[5 mg/kg/day\] to maintenance dose \[2 to 3 mg/kg/day\] or a flare after a minimum of 3 months on maintenance dose). Flare is defined as increase in signs and/or symptoms leading to escalation of therapy, which can be an increase in dose, a switch to a higher-potency class of TCS, or the start of another systemic non-steroidal immunosuppressive drug or * requirement for CSA at doses \>5 mg/kg/day, or duration beyond those specified in the prescribing information (\>1 year)

Exclusion criteria

1. Participation in a prior dupilumab clinical study 2. Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, before the screening visit 3. Hypersensitivity and/or intolerance to corticosteroids or to any other ingredients contained in the TCS product used in the study 4. Systemic CSA, systemic corticosteroids, or phototherapy within 4 weeks prior to screening, and azathioprine (AZA), methotrexate (MTX), mycophenolate mofetil (MMF), or Janus kinase (JAK) inhibitors within 8 weeks prior to screening 5. Treatment with TCI within 1 week before the screening visit 6. Treatment with biologics as follows: * Any cell-depleting agents including but not limited to rituximab: within 6 months before the screening visit, or until lymphocyte count returns to normal, whichever is longer * Other biologics: within 5 half-lives (if known) or 16 weeks prior to the screening visit, whichever is longer 7. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the screening visit 8. Treatment with a live (attenuated) vaccine within 12 weeks before the screening 9. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the screening or superficial skin infections within 1 week before the screening visit. NOTE: patients may be rescreened no sooner than 2 weeks after infection resolves 10. Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, tuberculosis \[TB\], histoplasmosis, Listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution; or unusually frequent, recurrent, or prolonged infections, per investigator judgment 11. Presence of any 1 of the following TB criteria: 1. A positive tuberculin skin test at the screening visit 2. A positive blood QuantiFERON®-TB or T-Spot test at the screening visit 3. Chest x-ray (posterior-anterior and lateral views) at screening or within 3 months before the screening visit (radiology report must be available) with results consistent with prior TB infection (including but not limited to apical scarring, apical fibrosis, or multiple calcified granuloma). This does not include non-caseating granulomata. NOTE: Any of these 3 TB tests will be performed on a country-by-country basis according to local guidelines only if required by regulatory authorities or ethics boards. 12. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening 13. Positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBc Ab), or hepatitis C antibody (HCV Ab) at the screening visit

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Eczema Area and Severity Index (EASI) 75 (≥75% Improvement From Baseline) at Week 16	Baseline, Week 16	The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured 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 16. The analysis population for efficacy analyses is the Full Analysis Set (FAS) which included all randomized participants. Efficacy analyses were based on the treatment allocated (as randomized).

Secondary

Measure	Time frame	Description
Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) at Week 16	Baseline, Week 16	The Pruritus NRS is an assessment tool used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would you rate your itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number of Participants Analyzed = Participants who were evaluable for this endpoint.
Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 16	Baseline, Week 16	The SCORAD is a clinical tool for assessing the severity of AD. 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). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number of Participants analyzed = Participants who were evaluable for this endpoint.
Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus NRS From Baseline to Week 16	Baseline to Week 16	Pruritus NRS is an assessment tool used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number of participants analyzed = participants who were evaluable for this endpoint.
Change From Baseline in Percent Body Surface Area (BSA) Involvement With Atopic Dermatitis (AD) at Week 16	Baseline, Week 16	BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]). It was reported as a percentage of all major body sections combined. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here number of participants analyzed = participants who were evaluable for this endpoint.
Percentage of Participants With Investigator Global Assessment (IGA) 0 or 1 (on the 0 to 4 IGA Scale) and a Reduction From Baseline of ≥2 Points at Week 16	Baseline, Week 16	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. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score of 0 or 1 and a reduction from baseline of ≥2 points at Week 16 were reported. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized).
Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 16	Baseline, Week 16	The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score is indicative of a poor QOL. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number of Participants Analyzed = Participants who were evaluable for this endpoint.
Change From Baseline in the Patient Oriented Eczema Measure (POEM) at Week 16	Baseline, Week 16	The 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 \[QOL\]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number of Participants Analyzed = participants who were evaluable for this endpoint.
Percentage of Participants With Eczema Area and Severity Index (EASI) Score (≥75% Improvement From Baseline) at Week 16 for Participants With Prior CSA Use	Baseline, Week 16	The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured 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 16. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number of Participants Analyzed = Participants who were evaluable for this endpoint.
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16	Baseline, Week 16	The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured 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. The analysis population for efficacy analyses is the FAS which included all randomized participants. Efficacy analyses were based on the treatment allocated (as randomized). Here number of participants analyzed = participants who were evaluable for this endpoint.
Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score at Week 16	Baseline, Week 16	The HADS is a 14-item scale, with 7 items relating to anxiety and 7 relating to depression. Each item on the questionnaire is scored from 0-3, for possible scores ranging from 0 (no symptoms) to 21 (severe symptoms) for each of the anxiety and depression subscales. Recommended cut-off scores for both subscales to identify psychiatric distress are: 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression. Scores less than 7 do not indicate psychiatric distress. Total score is the sum of the two sub-scores.
Percentage of Participants Achieving SCORAD 50 (≥50% Improvement From Baseline) at Week 16	Baseline, Week 16	The SCORAD is a clinical tool for assessing the severity of AD. 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). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized).
Percent Change From Baseline in the Total Global Individual Signs Score (GISS) at Week 16 (Erythema, Infiltration/ Papulation, Excoriations, Lichenification)	Baseline, Week 16	Individual components of the AD lesions (erythema, infiltration/ papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0= none, 1= mild, 2= moderate and 3= severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Full Analysis Set (FAS) included all randomized. Here Number of Participants Analyzed = Participants who were evaluable for this endpoint.
Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) Score at Week 2	Baseline, Week 2	Pruritus NRS is an assessment tool used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would you rate your itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number of Participants analyzed = Participants who were evaluable for this endpoint.
Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Treatment Period	Baseline to Week 16	Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. Safety analysis set (SAF) included all randomized participants who received any study drug; it was based on the treatment received (as treated).
Percentage of Participants Having at Least One Serious Treatment Emergent Adverse Event (TEAE) Through Treatment Period	Baseline to Week 16	Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. SAF included all randomized participants who received any study drug; it was based on the treatment received (as treated).
Percentage of Participants Having at Least One Treatment-Emergent Adverse Event (TEAE) Leading to Treatment Discontinuation Through Treatment Period	Baseline to Week 16	Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. SAF included all randomized participants who received any study drug; it was based on the treatment received (as treated).
Percentage of Participants With Treatment-Emergent Adverse Events Through Treatment Period	Baseline to Week 16	Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. SAF included all randomized participants who received any study drug; it was based on the treatment received (as treated).
Change From Baseline in Mean Weekly Dose of Topical Corticosteroid (TCS) Use During Treatment Period	Baseline to week 16	The type, amount, frequency, and potency of topical products used during the study were recorded at home by participants in a medication diary. Participants returned TCS tubes at each clinic visit up until week 16, and these tubes were weighed by the site staff to determine the actual amount of TCS used. During the 16-week placebo-controlled study treatment period, medium-potency TCS dosing frequency was symptom-based (IGA score) adjusted every 4 weeks per the protocol-specified tapering algorithm. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number Analyzed = Participants who were evaluable for this endpoint.

Countries

Austria, Belgium, Germany, Ireland, Netherlands, Poland, Russia, Slovakia, Spain, United Kingdom

Participant flow

Recruitment details

The study was conducted at 73 sites in Europe. A total of 390 participants were screened between 28 Jan 2016 and 14 Sep 2016. Of those, 325 participants were enrolled into the study and randomized. Sixty participants were considered screen failures, mostly due to unmet eligibility criteria.

Pre-assignment details

After providing informed consent, participants were assessed for study eligibility. Screening assessments were performed between day -28 & day -15, prior to randomization. Participants who met eligibility criteria at baseline (day 1) were randomized in a 1:1:1 ratio to receive dupilumab (weekly \[QW\] or every 2 weeks \[Q2W\]) or placebo.

Participants by arm

Arm	Count
Placebo QW + TCS Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	108
Dupilumab 300 mg Q2W + TCS Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	107
Dupilumab 300 mg QW + TCS Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).	110
Total	325

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Did Not Complete Follow-up Visits	1	0	0
Overall Study	Physician Decision	0	0	2
Overall Study	Transitioned into OLE study	99	98	100
Overall Study	Undecided	1	0	0
Overall Study	Withdrawal by Subject	0	1	0

Baseline characteristics

Characteristic	Placebo QW + TCS	Dupilumab 300 mg Q2W + TCS	Dupilumab 300 mg QW + TCS	Total
Age, Continuous	38.9 years STANDARD_DEVIATION 13.35	37.5 years STANDARD_DEVIATION 12.89	38.7 years STANDARD_DEVIATION 13.21	38.4 years STANDARD_DEVIATION 13.13
Body Surface Area (BSA) Involvement of Atopic Dermatitis	55.0 Score on a Scale STANDARD_DEVIATION 20.51	56.1 Score on a Scale STANDARD_DEVIATION 17.83	56.0 Score on a Scale STANDARD_DEVIATION 19.26	55.7 Score on a Scale STANDARD_DEVIATION 19.18
Dermatology Life Quality Index (DLQI) Total Score	13.2 Score on a Scale STANDARD_DEVIATION 7.6	14.5 Score on a Scale STANDARD_DEVIATION 7.63	13.8 Score on a Scale STANDARD_DEVIATION 8.03	13.8 Score on a Scale STANDARD_DEVIATION 7.75
Eczema Area and Severity Index (EASI) Score	32.9 Score on a Scale STANDARD_DEVIATION 10.8	33.3 Score on a Scale STANDARD_DEVIATION 9.93	33.1 Score on a Scale STANDARD_DEVIATION 11.02	33.1 Score on a Scale STANDARD_DEVIATION 10.56
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	1 Participants	5 Participants	9 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	101 Participants	99 Participants	101 Participants	301 Participants
Ethnicity (NIH/OMB) Not Reported/Missing	4 Participants	7 Participants	4 Participants	15 Participants
Global Individual Signs Score (GISS)	9.4 Score on a Scale STANDARD_DEVIATION 1.63	9.3 Score on a Scale STANDARD_DEVIATION 1.64	9.1 Score on a Scale STANDARD_DEVIATION 1.63	9.3 Score on a Scale STANDARD_DEVIATION 1.64
Investigator's Global Assessment (IGA) score IGA score = 3	56 Participants	57 Participants	58 Participants	171 Participants
Investigator's Global Assessment (IGA) score IGA score = 4	52 Participants	50 Participants	52 Participants	154 Participants
Patient Oriented Eczema Measure (POEM)	19.1 Score on a Scale STANDARD_DEVIATION 5.99	19.3 Score on a Scale STANDARD_DEVIATION 6.21	18.6 Score on a Scale STANDARD_DEVIATION 6.97	19.0 Score on a Scale STANDARD_DEVIATION 6.4
Peak Weekly Averaged Pruritus Numerical Rating Scale (NRS) score	6.4 Score on a Scale STANDARD_DEVIATION 2.23	6.6 Score on a Scale STANDARD_DEVIATION 2.1	6.2 Score on a Scale STANDARD_DEVIATION 2.01	6.4 Score on a Scale STANDARD_DEVIATION 2.11
Race (NIH/OMB) Asian	2 Participants	2 Participants	2 Participants	6 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) Not Reported / Missing	0 Participants	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Other	2 Participants	0 Participants	1 Participants	3 Participants
Race (NIH/OMB) White	104 Participants	104 Participants	105 Participants	313 Participants
SCORing Atopic Dermatitis (SCORAD) score	67.0 Score on a Scale STANDARD_DEVIATION 12.2	68.6 Score on a Scale STANDARD_DEVIATION 11.91	66.0 Score on a Scale STANDARD_DEVIATION 12.7	67.2 Score on a Scale STANDARD_DEVIATION 12.29
Sex: Female, Male Female	40 Participants	42 Participants	44 Participants	126 Participants
Sex: Female, Male Male	68 Participants	65 Participants	66 Participants	199 Participants
Total Hospital Anxiety and Depression Scale (HADS)	13.0 Score on a Scale STANDARD_DEVIATION 7.85	12.8 Score on a Scale STANDARD_DEVIATION 8.01	13.3 Score on a Scale STANDARD_DEVIATION 8.15	13.0 Score on a Scale STANDARD_DEVIATION 7.98

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 108	0 / 107	0 / 110
other Total, other adverse events	45 / 108	54 / 107	51 / 110
serious Total, serious adverse events	2 / 108	2 / 107	3 / 110

Outcome results

Primary

Percentage of Participants With Eczema Area and Severity Index (EASI) 75 (≥75% Improvement From Baseline) at Week 16

The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured 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 16. The analysis population for efficacy analyses is the Full Analysis Set (FAS) which included all randomized participants. Efficacy analyses were based on the treatment allocated (as randomized).

Time frame: Baseline, Week 16

Arm	Measure	Value (NUMBER)
Placebo QW + TCS	Percentage of Participants With Eczema Area and Severity Index (EASI) 75 (≥75% Improvement From Baseline) at Week 16	29.6 Percentage of Participants
Dupilumab 300 mg Q2W + TCS	Percentage of Participants With Eczema Area and Severity Index (EASI) 75 (≥75% Improvement From Baseline) at Week 16	62.6 Percentage of Participants
Dupilumab 300 mg QW + TCS	Percentage of Participants With Eczema Area and Severity Index (EASI) 75 (≥75% Improvement From Baseline) at Week 16	59.1 Percentage of Participants

Comparison: A hierarchical testing approach was used to control Type-1 error at 0.05 across 2 dose regimens. Difference is Dupilumab minus placebo. Confidence Interval (CI) calculated using normal approximation. Participants with missing values at Week 16 were categorized as non-responders at Week 16. Participants who used rescue treatment were categorized as non-responders from time rescue treatment was initiated.p-value: <0.000195% CI: [16.87, 42.05]Cochran-Mantel-Haenszel

Secondary

Change From Baseline in Mean Weekly Dose of Topical Corticosteroid (TCS) Use During Treatment Period

The type, amount, frequency, and potency of topical products used during the study were recorded at home by participants in a medication diary. Participants returned TCS tubes at each clinic visit up until week 16, and these tubes were weighed by the site staff to determine the actual amount of TCS used. During the 16-week placebo-controlled study treatment period, medium-potency TCS dosing frequency was symptom-based (IGA score) adjusted every 4 weeks per the protocol-specified tapering algorithm. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number Analyzed = Participants who were evaluable for this endpoint.

Time frame: Baseline to week 16

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo QW + TCS	Change From Baseline in Mean Weekly Dose of Topical Corticosteroid (TCS) Use During Treatment Period	25.1 Grams	Standard Error 1.48
Dupilumab 300 mg Q2W + TCS	Change From Baseline in Mean Weekly Dose of Topical Corticosteroid (TCS) Use During Treatment Period	15.0 Grams	Standard Error 1.51
Dupilumab 300 mg QW + TCS	Change From Baseline in Mean Weekly Dose of Topical Corticosteroid (TCS) Use During Treatment Period	17.5 Grams	Standard Error 1.49

Comparison: Hierarchical testing approach was used to control Type-1 error rate at 0.05 across 2 dose regimens.CI with p-value based on treatment difference(dupilumab vs. placebo) of LS mean percent change using MI with ANCOVA model with baseline measurement as covariate \& treatment, randomization strata(disease severity\[IGA 3 vs IGA 4\] \& prior CSA use \[Yes,No\]) as fixed factors.Efficacy data from participants who received rescue treatment were set to missing after timepoint of rescue, then imputed by MI.p-value: =0.000395% CI: [-11.64, -3.51]ANCOVA

Secondary

Change From Baseline in Percent Body Surface Area (BSA) Involvement With Atopic Dermatitis (AD) at Week 16

BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]). It was reported as a percentage of all major body sections combined. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here number of participants analyzed = participants who were evaluable for this endpoint.

Time frame: Baseline, Week 16

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo QW + TCS	Change From Baseline in Percent Body Surface Area (BSA) Involvement With Atopic Dermatitis (AD) at Week 16	-19.57 Percent BSA	Standard Error 1.798
Dupilumab 300 mg Q2W + TCS	Change From Baseline in Percent Body Surface Area (BSA) Involvement With Atopic Dermatitis (AD) at Week 16	-39.23 Percent BSA	Standard Error 1.715
Dupilumab 300 mg QW + TCS	Change From Baseline in Percent Body Surface Area (BSA) Involvement With Atopic Dermatitis (AD) at Week 16	-37.52 Percent BSA	Standard Error 1.69

Comparison: Hierarchical testing approach was used to control Type-1 error rate at 0.05 across 2 dose regimens.CI with p-value is based on treatment difference(dupilumab vs. placebo) of LS mean percent change using MI with ANCOVA model with baseline measurement as covariate \& treatment,randomization strata(disease severity\[IGA 3 vs IGA 4\] \& prior CSA use \[Yes,No\]) as fixed factors. Efficacy data from participants who received rescue treatment were set to missing after timepoint of rescue, then imputed by MIp-value: <0.000195% CI: [-22.706, -13.197]ANCOVA

Secondary

Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 16

The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score is indicative of a poor QOL. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number of Participants Analyzed = Participants who were evaluable for this endpoint.

Time frame: Baseline, Week 16

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo QW + TCS	Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 16	-4.5 Score on a Scale	Standard Error 0.49
Dupilumab 300 mg Q2W + TCS	Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 16	-9.5 Score on a Scale	Standard Error 0.46
Dupilumab 300 mg QW + TCS	Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 16	-8.8 Score on a Scale	Standard Error 0.45

Comparison: Hierarchical testing approach was used to control Type-1 error rate at 0.05 across 2 dose regimens.CI with p-value based on treatment difference(dupilumab vs. placebo) of LS mean percent change using MI with ANCOVA model with baseline measurement as covariate \& treatment, randomization strata(disease severity\[IGA 3 vs IGA 4\] \& prior CSA use \[Yes,No\])as fixed factors. Efficacy data from participants who received rescue treatment were set to missing after timepoint of rescue, then imputed by MI.p-value: <0.000195% CI: [-6.31, -3.74]ANCOVA

Secondary

Change From Baseline in the Patient Oriented Eczema Measure (POEM) at Week 16

The 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 \[QOL\]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number of Participants Analyzed = participants who were evaluable for this endpoint.

Time frame: Baseline, Week 16

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo QW + TCS	Change From Baseline in the Patient Oriented Eczema Measure (POEM) at Week 16	-4.3 Score on a Scale	Standard Error 0.62
Dupilumab 300 mg Q2W + TCS	Change From Baseline in the Patient Oriented Eczema Measure (POEM) at Week 16	-11.9 Score on a Scale	Standard Error 0.6
Dupilumab 300 mg QW + TCS	Change From Baseline in the Patient Oriented Eczema Measure (POEM) at Week 16	-11.4 Score on a Scale	Standard Error 0.59

Comparison: Hierarchical testing approach was used to control Type-1 error rate at 0.05 across 2 dose regimens.CI with p-value based on treatment difference(dupilumab vs. placebo) of LS mean percent change using MI with ANCOVA model with baseline measurement as covariate \& treatment, randomization strata(disease severity\[IGA 3 vs IGA 4\] \& prior CSA use \[Yes,No\])as fixed factors. Efficacy data from participants who received rescue treatment were set to missing after timepoint of rescue, then imputed by MI.p-value: <0.000195% CI: [-8.78, -5.47]ANCOVA

Comparison: Hierarchical testing approach was used to control Type-1 error rate at 0.05 across 2 dose regimens.CI with p-value based on treatment difference(dupilumab vs. placebo) of LS mean percent change using MI with ANCOVA model with baseline measurement as covariate \& treatment, randomization strata(disease severity\[IGA 3 vs IGA 4\] \& prior CSA use \[Yes,No\])as fixed factors. Efficacy data from participants who received rescue treatment were set to missing after timepoint of rescue, then imputed by MI.p-value: <0.000195% CI: [-9.29, -5.97]ANCOVA

Secondary

Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score at Week 16

The HADS is a 14-item scale, with 7 items relating to anxiety and 7 relating to depression. Each item on the questionnaire is scored from 0-3, for possible scores ranging from 0 (no symptoms) to 21 (severe symptoms) for each of the anxiety and depression subscales. Recommended cut-off scores for both subscales to identify psychiatric distress are: 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression. Scores less than 7 do not indicate psychiatric distress. Total score is the sum of the two sub-scores.

Time frame: Baseline, Week 16

Population: Analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number of Participants Analyzed = Participants who were evaluable for this endpoint.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo QW + TCS	Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score at Week 16	-2.3 Score on a Scale	Standard Error 0.56
Dupilumab 300 mg Q2W + TCS	Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score at Week 16	-6.1 Score on a Scale	Standard Error 0.54
Dupilumab 300 mg QW + TCS	Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score at Week 16	-5.2 Score on a Scale	Standard Error 0.53

Secondary

Percentage of Participants Achieving SCORAD 50 (≥50% Improvement From Baseline) at Week 16

The SCORAD is a clinical tool for assessing the severity of AD. 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). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized).

Time frame: Baseline, Week 16

Arm	Measure	Value (NUMBER)
Placebo QW + TCS	Percentage of Participants Achieving SCORAD 50 (≥50% Improvement From Baseline) at Week 16	25.9 Percentage of Participants
Dupilumab 300 mg Q2W + TCS	Percentage of Participants Achieving SCORAD 50 (≥50% Improvement From Baseline) at Week 16	66.4 Percentage of Participants
Dupilumab 300 mg QW + TCS	Percentage of Participants Achieving SCORAD 50 (≥50% Improvement From Baseline) at Week 16	55.5 Percentage of Participants

Comparison: A hierarchical testing approach was used to control Type-1 error at 0.05 across the 2 dose regimens. Difference is dupilumab minus placebo. CI calculated using normal approximation. P-values were derived by CMH test stratified by disease severity (IGA 3 vs IGA 4) and prior CSA use (Yes,No). Participants who used rescue treatment were categorized as non-responders from time rescue treatment was initiated. Participants with missing values at Week 16 were categorized as non-responders at Week 16.p-value: <0.000195% CI: [17.1, 41.96]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants Having at Least One Serious Treatment Emergent Adverse Event (TEAE) Through Treatment Period

Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. SAF included all randomized participants who received any study drug; it was based on the treatment received (as treated).

Time frame: Baseline to Week 16

Arm	Measure	Value (NUMBER)
Placebo QW + TCS	Percentage of Participants Having at Least One Serious Treatment Emergent Adverse Event (TEAE) Through Treatment Period	1.9 Percentage of Participants
Dupilumab 300 mg Q2W + TCS	Percentage of Participants Having at Least One Serious Treatment Emergent Adverse Event (TEAE) Through Treatment Period	1.9 Percentage of Participants
Dupilumab 300 mg QW + TCS	Percentage of Participants Having at Least One Serious Treatment Emergent Adverse Event (TEAE) Through Treatment Period	1.8 Percentage of Participants

Secondary

Percentage of Participants Having at Least One Treatment-Emergent Adverse Event (TEAE) Leading to Treatment Discontinuation Through Treatment Period

Time frame: Baseline to Week 16

Arm	Measure	Value (NUMBER)
Placebo QW + TCS	Percentage of Participants Having at Least One Treatment-Emergent Adverse Event (TEAE) Leading to Treatment Discontinuation Through Treatment Period	0.9 Percentage of participants
Dupilumab 300 mg Q2W + TCS	Percentage of Participants Having at Least One Treatment-Emergent Adverse Event (TEAE) Leading to Treatment Discontinuation Through Treatment Period	0 Percentage of participants
Dupilumab 300 mg QW + TCS	Percentage of Participants Having at Least One Treatment-Emergent Adverse Event (TEAE) Leading to Treatment Discontinuation Through Treatment Period	1.8 Percentage of participants

Comparison: A hierarchical testing approach was used to control Type-1 error at 0.05 across the 2 dose regimens. Difference is dupilumab minus placebo. CI calculated using normal approximation. P-values were derived by CMH test stratified by disease severity (IGA 3 vs IGA 4) and prior CSA use (Yes,No). Participants who used rescue treatment were categorized as non-responders from time rescue treatment was initiated. Participants with missing values at Week 16 were categorized as non-responders at Week 16.p-value: =0.561995% CI: [-2.19, 3.97]Cochran-Mantel-Haenszel

Comparison: A hierarchical testing approach was used to control Type-1 error at 0.05 across the 2 dose regimens. Difference is dupilumab minus placebo. CI calculated using normal approximation. P-values were derived by CMH test stratified by disease severity (IGA 3 vs IGA 4) and prior CSA use (Yes,No). Participants who used rescue treatment were categorized as non-responders from time rescue treatment was initiated. Participants with missing values at Week 16 were categorized as non-responders at Week 16.p-value: =0.324195% CI: [-2.73, 0.88]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants With Eczema Area and Severity Index (EASI) Score (≥75% Improvement From Baseline) at Week 16 for Participants With Prior CSA Use

The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured 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 16. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number of Participants Analyzed = Participants who were evaluable for this endpoint.

Time frame: Baseline, Week 16

Arm	Measure	Value (NUMBER)
Placebo QW + TCS	Percentage of Participants With Eczema Area and Severity Index (EASI) Score (≥75% Improvement From Baseline) at Week 16 for Participants With Prior CSA Use	26.4 Percentage of Participants
Dupilumab 300 mg Q2W + TCS	Percentage of Participants With Eczema Area and Severity Index (EASI) Score (≥75% Improvement From Baseline) at Week 16 for Participants With Prior CSA Use	58.0 Percentage of Participants
Dupilumab 300 mg QW + TCS	Percentage of Participants With Eczema Area and Severity Index (EASI) Score (≥75% Improvement From Baseline) at Week 16 for Participants With Prior CSA Use	56.5 Percentage of Participants

Comparison: A hierarchical testing approach was used to control Type-1 error at 0.05 across the 2 dose regimens. Difference is dupilumab minus placebo. CI calculated using normal approximation. P-values were derived by CMH test stratified by disease severity (IGA 3 vs IGA 4) and prior CSA use (Yes,No). Participants who used rescue treatment were categorized as non-responders from time rescue treatment was initiated. Participants with missing values at Week 16 were categorized as non-responders at Week 16.p-value: =0.000295% CI: [14.63, 45.64]Cochran-Mantel-Haenszel

Comparison: Hierarchical testing approach was used to control Type-1 error at 0.05 across the 2 dose regimens. Difference is dupilumab minus placebo. CI calculated using normal approximation. P-values derived by CMH test stratified by disease severity (IGA 3 vs IGA 4) and prior CSA use (Yes,No). Participants who used rescue treatment were categorized as non-responders from time rescue treatment was initiated. Participants with missing values at Week 16 were categorized as non-responders at Week 16.p-value: =0.000195% CI: [16.11, 47.05]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus NRS From Baseline to Week 16

Pruritus NRS is an assessment tool used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number of participants analyzed = participants who were evaluable for this endpoint.

Time frame: Baseline to Week 16

Arm	Measure	Value (NUMBER)
Placebo QW + TCS	Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus NRS From Baseline to Week 16	14.3 Percentage of participants
Dupilumab 300 mg Q2W + TCS	Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus NRS From Baseline to Week 16	45.7 Percentage of participants
Dupilumab 300 mg QW + TCS	Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus NRS From Baseline to Week 16	40.4 Percentage of participants

Secondary

Percentage of Participants With Investigator Global Assessment (IGA) 0 or 1 (on the 0 to 4 IGA Scale) and a Reduction From Baseline of ≥2 Points at Week 16

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. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score of 0 or 1 and a reduction from baseline of ≥2 points at Week 16 were reported. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized).

Time frame: Baseline, Week 16

Arm	Measure	Value (NUMBER)
Placebo QW + TCS	Percentage of Participants With Investigator Global Assessment (IGA) 0 or 1 (on the 0 to 4 IGA Scale) and a Reduction From Baseline of ≥2 Points at Week 16	13.9 Percentage of Participants
Dupilumab 300 mg Q2W + TCS	Percentage of Participants With Investigator Global Assessment (IGA) 0 or 1 (on the 0 to 4 IGA Scale) and a Reduction From Baseline of ≥2 Points at Week 16	40.2 Percentage of Participants
Dupilumab 300 mg QW + TCS	Percentage of Participants With Investigator Global Assessment (IGA) 0 or 1 (on the 0 to 4 IGA Scale) and a Reduction From Baseline of ≥2 Points at Week 16	39.1 Percentage of Participants

Secondary

Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Treatment Period

Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. Safety analysis set (SAF) included all randomized participants who received any study drug; it was based on the treatment received (as treated).

Time frame: Baseline to Week 16

Arm	Measure	Value (NUMBER)
Placebo QW + TCS	Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Treatment Period	8.3 Percentage of Participants
Dupilumab 300 mg Q2W + TCS	Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Treatment Period	1.9 Percentage of Participants
Dupilumab 300 mg QW + TCS	Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Treatment Period	3.6 Percentage of Participants

Comparison: A hierarchical testing approach was used to control Type-1 error at 0.05 across the 2 dose regimens. Difference is dupilumab minus placebo. CI calculated using normal approximation. P-values were derived by CMH test stratified by disease severity (IGA 3 vs IGA 4) and prior CSA use (Yes,No). Participants who used rescue treatment were categorized as non-responders from time rescue treatment was initiated. Participants with missing values at Week 16 were categorized as non-responders at Week 16.p-value: =0.148695% CI: [-10.97, 1.58]Cochran-Mantel-Haenszel

Comparison: A hierarchical testing approach was used to control Type-1 error at 0.05 across the 2 dose regimens. Difference is dupilumab minus placebo. CI calculated using normal approximation. P-values were derived by CMH test stratified by disease severity (IGA 3 vs IGA 4) and prior CSA use (Yes,No). Participants who used rescue treatment were categorized as non-responders from time rescue treatment was initiated. Participants with missing values at Week 16 were categorized as non-responders at Week 16.p-value: =0.031995% CI: [-12.27, -0.65]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants With Treatment-Emergent Adverse Events Through Treatment Period

Time frame: Baseline to Week 16

Arm	Measure	Value (NUMBER)
Placebo QW + TCS	Percentage of Participants With Treatment-Emergent Adverse Events Through Treatment Period	69.4 Percentage of participants
Dupilumab 300 mg Q2W + TCS	Percentage of Participants With Treatment-Emergent Adverse Events Through Treatment Period	72.0 Percentage of participants
Dupilumab 300 mg QW + TCS	Percentage of Participants With Treatment-Emergent Adverse Events Through Treatment Period	69.1 Percentage of participants

Comparison: A hierarchical testing approach was used to control Type-1 error at 0.05 across the 2 dose regimens. Difference is dupilumab minus placebo. CI calculated using normal approximation. P-values were derived by CMH test stratified by disease severity (IGA 3 vs IGA 4) and prior CSA use (Yes,No). Participants who used rescue treatment were categorized as non-responders from time rescue treatment was initiated. Participants with missing values at Week 16 were categorized as non-responders at Week 16.p-value: =0.951895% CI: [-12.6, 11.9]Cochran-Mantel-Haenszel

Comparison: A hierarchical testing approach was used to control Type-1 error at 0.05 across the 2 dose regimens. Difference is dupilumab minus placebo. CI calculated using normal approximation. P-values were derived by CMH test stratified by disease severity (IGA 3 vs IGA 4) and prior CSA use (Yes,No). Participants who used rescue treatment were categorized as non-responders from time rescue treatment was initiated. Participants with missing values at Week 16 were categorized as non-responders at Week 16.p-value: =0.683395% CI: [-9.64, 14.68]Cochran-Mantel-Haenszel

Secondary

Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16

The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured 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. The analysis population for efficacy analyses is the FAS which included all randomized participants. Efficacy analyses were based on the treatment allocated (as randomized). Here number of participants analyzed = participants who were evaluable for this endpoint.

Time frame: Baseline, Week 16

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo QW + TCS	Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16	-46.6 Percent Change	Standard Error 2.76
Dupilumab 300 mg Q2W + TCS	Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16	-79.8 Percent Change	Standard Error 2.59
Dupilumab 300 mg QW + TCS	Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16	-78.2 Percent Change	Standard Error 2.55

Comparison: Hierarchical testing approach to control Type-1 error rate at 0.05 across 2 dose regimens.CI w/p-value based on treatment difference(dupilumab vs placebo) of LS mean percent change using multiple imputation (MI) w/ANCOVA model w/baseline measurement as covariate \& treatment, randomization strata(disease severity\[IGA 3 vs IGA 4\] \& prior CSA use\[Yes,No\]) as fixed factors.Efficacy data from participants who received rescue treatment were set to missing after timepoint of rescue, then imputed by MIp-value: <0.000195% CI: [-38.85, -24.3]ANCOVA

Comparison: Hierarchical testing approach was used to control Type-1 error rate at 0.05 across 2 dose regimens.CI with p-value based on treatment difference(dupilumab vs. placebo) of LS mean percent change using MI with ANCOVA model with baseline measurement as covariate \& treatment, randomization strata(disease severity\[IGA 3 vs IGA 4\] \& prior CSA use \[Yes,No\]) as fixed factors. Efficacy data from participants who received rescue treatment were set to missing after timepoint of rescue \& then imputed by MI.p-value: <0.000195% CI: [-40.42, -25.88]ANCOVA

Secondary

Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 16

Time frame: Baseline, Week 16

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo QW + TCS	Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 16	-29.5 Percent Change	Standard Error 2.55
Dupilumab 300 mg Q2W + TCS	Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 16	-62.4 Percent Change	Standard Error 2.48
Dupilumab 300 mg QW + TCS	Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 16	-58.3 Percent Change	Standard Error 2.45

Secondary

Percent Change From Baseline in the Total Global Individual Signs Score (GISS) at Week 16 (Erythema, Infiltration/ Papulation, Excoriations, Lichenification)

Individual components of the AD lesions (erythema, infiltration/ papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0= none, 1= mild, 2= moderate and 3= severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Full Analysis Set (FAS) included all randomized. Here Number of Participants Analyzed = Participants who were evaluable for this endpoint.

Time frame: Baseline, Week 16

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo QW + TCS	Percent Change From Baseline in the Total Global Individual Signs Score (GISS) at Week 16 (Erythema, Infiltration/ Papulation, Excoriations, Lichenification)	-29.0 Percent Change	Standard Error 2.75
Dupilumab 300 mg Q2W + TCS	Percent Change From Baseline in the Total Global Individual Signs Score (GISS) at Week 16 (Erythema, Infiltration/ Papulation, Excoriations, Lichenification)	-55.2 Percent Change	Standard Error 2.66
Dupilumab 300 mg QW + TCS	Percent Change From Baseline in the Total Global Individual Signs Score (GISS) at Week 16 (Erythema, Infiltration/ Papulation, Excoriations, Lichenification)	-53.3 Percent Change	Standard Error 2.65

Comparison: A hierarchical testing approach was used to control Type-1 error rate at 0.05 across 2 dose regimens.CI with p-value based on treatment difference(dupilumab group vs. placebo)of LS mean percent change using MI with ANCOVA with baseline measurement as covariate \& treatment,randomization strata(disease severity\[IGA 3 vs IGA 4\] \& prior CSA use\[Yes,No\])as fixed factors.Efficacy data from participants who received rescue treatment were set to missing after timepoint of rescue, then imputed by MI.p-value: <0.000195% CI: [-31.63, -16.88]ANCOVA

Comparison: Hierarchical testing approach was used to control Type-1 error rate at 0.05 across 2 dose regimens.CI with p-value based on treatment difference(dupilumab vs. placebo) of LS mean percent change using MI with ANCOVA model with baseline measurement as covariate \& treatment, randomization strata (disease severity\[IGA 3 vs IGA 4\] \& prior CSA use \[Yes,No\]) as fixed factors.Efficacy data from participants who received rescue treatment were set to missing after timepoint of rescue, then imputed by MI.p-value: <0.000195% CI: [-33.49, -18.86]ANCOVA

Secondary

Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) at Week 16

The Pruritus NRS is an assessment tool used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would you rate your itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number of Participants Analyzed = Participants who were evaluable for this endpoint.

Time frame: Baseline, Week 16

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo QW + TCS	Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) at Week 16	-25.4 Percent Change	Standard Error 3.39
Dupilumab 300 mg Q2W + TCS	Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) at Week 16	-53.9 Percent Change	Standard Error 3.14
Dupilumab 300 mg QW + TCS	Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) at Week 16	-51.7 Percent Change	Standard Error 3.09

Secondary

Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) Score at Week 2

Pruritus NRS is an assessment tool used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would you rate your itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here Number of Participants analyzed = Participants who were evaluable for this endpoint.

Time frame: Baseline, Week 2

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo QW + TCS	Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) Score at Week 2	-10.0 Percent Change	Standard Error 2.24
Dupilumab 300 mg Q2W + TCS	Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) Score at Week 2	-17.2 Percent Change	Standard Error 2.25
Dupilumab 300 mg QW + TCS	Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) Score at Week 2	-19.7 Percent Change	Standard Error 2.21

Comparison: Hierarchical testing approach was used to control Type-1 error rate at 0.05 across 2 dose regimens. CI with p-value based on treatment difference(dupilumab vs. placebo) of LS mean percent change using MI with ANCOVA model with baseline measurement as covariate \& treatment, randomization strata(disease severity\[IGA 3 vs IGA 4\] \& prior CSA use \[Yes,No\]) as fixed factors.Efficacy data from participants who received rescue treatment were set to missing after timepoint of rescue, then imputed by MI.p-value: =0.001795% CI: [-15.8, -3.66]ANCOVA

Source: ClinicalTrials.gov · Data processed: Mar 3, 2026

A Study to Assess the Efficacy and Safety of Dupilumab in Participants With Severe Atopic Dermatitis (AD) That Are Not Controlled With Oral Cyclosporine A (CSA) or for Those Who Cannot Take Oral CSA Because it is Not Medically Advisable

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Percentage of Participants With Eczema Area and Severity Index (EASI) 75 (≥75% Improvement From Baseline) at Week 16

Change From Baseline in Mean Weekly Dose of Topical Corticosteroid (TCS) Use During Treatment Period

Change From Baseline in Percent Body Surface Area (BSA) Involvement With Atopic Dermatitis (AD) at Week 16

Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 16

Change From Baseline in the Patient Oriented Eczema Measure (POEM) at Week 16

Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score at Week 16

Percentage of Participants Achieving SCORAD 50 (≥50% Improvement From Baseline) at Week 16

Percentage of Participants Having at Least One Serious Treatment Emergent Adverse Event (TEAE) Through Treatment Period

Percentage of Participants Having at Least One Treatment-Emergent Adverse Event (TEAE) Leading to Treatment Discontinuation Through Treatment Period

Percentage of Participants With Eczema Area and Severity Index (EASI) Score (≥75% Improvement From Baseline) at Week 16 for Participants With Prior CSA Use

Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus NRS From Baseline to Week 16

Percentage of Participants With Investigator Global Assessment (IGA) 0 or 1 (on the 0 to 4 IGA Scale) and a Reduction From Baseline of ≥2 Points at Week 16

Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Treatment Period

Percentage of Participants With Treatment-Emergent Adverse Events Through Treatment Period

Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16

Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 16

Percent Change From Baseline in the Total Global Individual Signs Score (GISS) at Week 16 (Erythema, Infiltration/ Papulation, Excoriations, Lichenification)

Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) at Week 16

Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) Score at Week 2