Study to Assess the Efficacy and Long-term Safety of Dupilumab (REGN668/SAR231893) in Adult Participants With Moderate-to-Severe Atopic Dermatitis

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 0 or 1 and a reduction from baseline of ≥2 points at Week 16 were reported.

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the Full Analysis Set (FAS), which included all randomized participants. Efficacy analyses were based on the treatment allocated by interactive voice response system/ interactive web response system (IVRS/IWRS) at randomization (as randomized).

The DLQI was 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 was indicative of a poor QOL.

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

The DLQI was 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 was indicative of a poor QOL.

Time frame: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

HADS is a fourteen item scale. Seven of the items relate to anxiety and seven items relate to depression. Each item on the questionnaire scored from 0 (minimum score) - 3 (maximum score) and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported as 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression.

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

HADS is a fourteen item scale. Seven of the items relate to anxiety and seven items relate to depression. Each item on the questionnaire is scored from 0 (minimum score) - 3 (maximum score) and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported as 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression.

Time frame: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

The POEM was a 7-item questionnaire that assessed 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 \[QOL\]).

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

The POEM was 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 \[QOL\]).

Time frame: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

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.

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

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.

Time frame: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

Pruritus NRS was an assessment tool that was 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 \[0 = no itch; 10 = worst itch imaginable\]).

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

Atopic dermatitis (AD) flares were defined as worsening of the disease that required escalation/intensification of AD treatment. Number of flares occurred in the participants starting from first dose through Week 52 were reported.

Time frame: Baseline up to Week 52

Population: All safety analysis were performed on safety analysis set (SAF) that included all randomized participants who received any study drug, and were analyzed as-treated.

Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. 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.

Time frame: Baseline up to Week 52

Population: All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.

Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = Infection and Infestations or SOC = Skin and Subcutaneous Tissue Disorders. Blinded adjudication was performed and finalized by the study medical monitor before database lock.

Time frame: Baseline up to Week 52

Population: All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.

Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = Infection and Infestations or SOC = Skin and Subcutaneous Tissue Disorders. Blinded adjudication was performed and finalized by the study medical monitor before database lock.

Time frame: Baseline up to Week 52

Population: All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.

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 16.

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

The EASI score was used to measure the severity and extent of 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 52.

Time frame: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

Pruritus NRS was an assessment tool that was 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 ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported.

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥3.

Pruritus NRS was an assessment tool that was 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 ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 52 were reported.

Time frame: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥3.

Pruritus NRS was an assessment tool that was 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.

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.

Pruritus NRS was an assessment tool that was 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 2 were reported.

Time frame: Baseline to Week 2

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.

Pruritus NRS was an assessment tool that was 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 24 were reported.

Time frame: Baseline to Week 24

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.

Pruritus NRS was an assessment tool that was 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 4 were reported.

Time frame: Baseline to Week 4

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.

Pruritus NRS was an assessment tool that was 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 52 were reported.

Time frame: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with baseline peak pruritus NRS score ≥4.

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 52 were reported.

Time frame: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

Any untoward medical occurrence in a participants who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = Infection and Infestations or SOC = Skin and Subcutaneous Tissue Disorders. Blinded adjudication was performed and finalized by the study medical monitor before database lock.

Time frame: Baseline up to Week 52

Population: All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.

Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = Infection and Infestations or SOC = Skin and Subcutaneous Tissue Disorders. Blinded adjudication was performed and finalized by the study medical monitor before database lock.

Time frame: Baseline up to Week 52

Population: All safety analysis were performed on SAF that included all randomized participants who received any study drug, and was analyzed as-treated.

The EASI score was used to measure the severity and extent of 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.

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

The EASI score was used to measure the severity and extent of 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.

Time frame: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

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).

Time frame: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

SCORAD was a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

SCORAD was a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).

Time frame: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.

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).

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

Pruritus NRS was an assessment tool that was 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 \[0 = no itch; 10 = worst itch imaginable\]).

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

Pruritus NRS was an assessment tool that was 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 \[0 = no itch; 10 = worst itch imaginable\]).

Time frame: Baseline to Week 2

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

Proportion of topical AD medication-free days through Week 52 was calculated as the number of days that a participant used neither topical corticosteroid (TCS)/ topical calcineurin inhibitors (TCI) nor system rescue therapy divided by the study days of each period.

Time frame: Baseline to Week 52

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).

ACQ-5 questionnaire was a validated questionnaire comprising of 5 questions for asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath, and wheeze. Participants were asked to rate their asthma symptoms during the previous week on a 7-point scale as 0=no impairment, 6=maximum impairment. ACQ-5 score was the mean of the 5 questions and range between 0 (totally controlled) and 6 (severely uncontrolled) (a higher score indicated lower asthma control). The ACQ-5 questionnaire was administered only to the participants with a medical history of asthma.

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with ACQ-5 value at baseline.

The SNOT 22 was a validated measure of health related quality of life in sinonasal disease. It was a 22 item questionnaire with each item assigned a score ranging from 0-5. The total score may range from 0 (no disease) -110 (worst disease) (lower scores represent better health related quality of life). The SNOT-22 was administered only to participants with chronic inflammatory conditions of the nasal mucosa and/or paranasal sinuses.

Time frame: Baseline to Week 16

Population: All efficacy analyses were performed on the FAS, which included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized). Here, number of participants analyzed = participants with available data for this endpoint.