Efficacy and Safety of REGN3500 Monotherapy and Combination of REGN3500 Plus Dupilumab in Adult Patients With Moderate-to-Severe Atopic Dermatitis

The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, induration, 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. Percent change from baseline in EASI score at Week 16 based on observed values set to missing after rescue treatment was reported. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

The EASI score was used to measure the severity and extent of AD and measures erythema, induration, 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. Absolute change from baseline in EASI score at Week 16 based on all observed values regardless of rescue treatment was reported.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

The EASI score was used to measure the severity and extent of AD and measures erythema, induration, 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. Absolute change from baseline in EASI score at Week 16 was reported.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

BSA affected by AD will be assessed for each section of the body using the rule of nines (the possible highest score for each region is: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]) and will be reported as a percentage of all major body sections combined. The proportion assigned to different body regions is different in younger children as compared to older children (head and neck area is assigned a higher proportion in younger children as compared to older children). Due to study discontinuation, not all planned participants were enrolled. For those already enrolled, the study drug was discontinued and participants were transitioned to post-treatment follow-up period. A large amount of data remained uncollected as not all enrolled participants completed all planned study visits and procedures for assessments for some endpoints. Therefore, this endpoint was removed and no data was collected for this outcome measure.

Time frame: Week 16

Population: Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

Pruritus NRS was an assessment tool used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, using an electronic questionnaire (e-diary). 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 \[0 = no itch; 10 = worst itch imaginable\]). Absolute change from baseline in weekly average of daily Peak Pruritus NRS score at Week 16 based on all observed values regardless of rescue treatment was reported.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

Pruritus NRS was an assessment tool used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, using an electronic questionnaire (e-diary). 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 \[0 = no itch; 10 = worst itch imaginable\]). Absolute change from baseline in weekly average of daily Peak Pruritus NRS score at Week 16 based on observed values set to missing after rescue treatment was reported.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

Treatment-Emergent (TE) ADA: any positive post baseline assay response when baseline results were negative/missing. TE ADA responses were further classified as: - persistent (treatment-emergent positive ADA response detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period \[based on nominal sampling time\], with no ADA-negative samples in-between, regardless of any missing samples or a positive response at the last ADA sampling time point),- indeterminate (a positive assay response at the last collection time point only, regardless of any missing samples), - transient (not persistent/indeterminate, regardless of any missing samples). Here, Number of Participants Analysed signifies those participants who were evaluable for this endpoint.

Time frame: Baseline up to Week 36

Population: The ADA analysis set (AAS) included all participants who received any study drug and had at least 1 non-missing ADA result in the respective ADA assays, after the first dose of the study drug.

Adverse Event (AE): any untoward medical occurrence in a participant administered a study drug which may/may not have a causal relationship with study drug. Serious AE (SAE): any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial/prolonged in-participant hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. TEAE: AEs starting/worsening after first intake of study drug. TEAEs included: SAEs and Non-SAEs. AESI included: Anaphylactic reactions; Systemic/severe hypersensitivity reactions; Malignancy; Helminthic infections; Suicide-related events; Severe injection site reactions; Mycosis fungoides/other forms of cutaneous T-cell lymphoma; any clinical endoparasitosis; Conjunctivitis and significant Alanine aminotransferase (ALT) elevation. Number of participants with TEAEs, Serious TEAES and AESIs from baseline up to Week 16 were reported.

Time frame: Baseline up to Week 16

Population: Safety analysis set (SAF) included all randomized participants who received any study drug and was based on the treatment received (as treated).

AE: any untoward medical occurrence in a participant administered a study drug which may/may not have a causal relationship with study drug. SAE: any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial/prolonged in-participant hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. TEAE: AEs starting/worsening after first intake of study drug. TEAEs included both SAEs and Non-SAEs. AESI included: Anaphylactic reactions; Systemic/severe hypersensitivity reactions; Malignancy; Helminthic infections; Suicide-related events; Severe injection site reactions; Mycosis fungoides/other forms of cutaneous T-cell lymphoma; any clinical endoparasitosis; Conjunctivitis and significant ALT elevation. Number of participants with TEAEs, Serious TEAES and AESIs from baseline up to Week 36 were reported.

Time frame: Baseline up to Week 36

Population: SAF included all randomized participants who received any study drug and was based on the treatment received (as treated).

The EASI score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Percentage of participants who achieved EASI-50 (≥50% Improvement from baseline) at Week 16 were based on all observed values regardless of rescue treatment were reported.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

The EASI score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Percentage of participants who achieved EASI-50 (≥50% Improvement from baseline) at Week 16 based on observed values set to missing after rescue treatment were reported. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

The EASI score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Percentage of participants who achieved EASI-75 (≥75% Improvement from baseline) at Week 16 based on all observed values regardless of rescue treatment were reported.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

The EASI score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Percentage of participants who achieved EASI-75 (≥75% Improvement from baseline) at Week 16 based on observed values set to missing after rescue treatment were reported. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders. Percentage of participants who achieved EASI-75 (\>= 75% Improvement from baseline) at Week 16 based on observed values set to missing after rescue treatment were reported. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

The EASI score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Percentage of participants who achieved EASI-90 (≥90% Improvement from baseline) at Week 16 based on all observed values regardless of rescue treatment were reported.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

The EASI score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Percentage of participants who achieved EASI-90 (≥90% Improvement from baseline) at Week 16 based on observed values set to missing after rescue treatment were reported. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

IGA was 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 was an IGA score of 0 (clear) or 1 (almost clear). Participants with both IGA score of 0 or 1 and a reduction from baseline of ≥2 points at Week 16 based on all observed values regardless of rescue treatment were reported.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

IGA was 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 was an IGA score of 0 (clear) or 1 (almost clear). Participants with both IGA score of 0 or 1 and a reduction from baseline of \>= 2 points at Week 16 based on observed values set to missing after rescue treatment were reported. Values after first rescue treatment were set to missing and participants with missing IGA score at Week 16 were counted as non-responders.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

Pruritus NRS was an assessment tool used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, using an electronic questionnaire (e-diary). 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 \[0 = no itch; 10 = worst itch imaginable\]). Percentage of participants with improvement of weekly average of daily peak pruritus NRS from baseline to Week 16 based on all observed values regardless of rescue treatment were reported.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

Pruritus NRS was an assessment tool used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, using an electronic questionnaire (e-diary). 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 \[0 = no itch; 10 = worst itch imaginable\]). Percentage of participants with improvement of weekly average of daily peak pruritus NRS from baseline to Week 16 based on observed values set to missing after rescue treatment were reported. Values after first rescue treatment were set to missing and participants with missing NRS at Week 16 were counted as non-responders.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

The EASI score was used to measure the severity and extent of AD and measures erythema, induration, 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. Percent change from baseline in EASI score at Week 16 based on all observed values regardless of rescue treatment was reported.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

Pruritus NRS was an assessment tool used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, using an electronic questionnaire (e-diary). 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 \[0 = no itch; 10 = worst itch imaginable\]). Percent change from baseline in weekly average of daily peak pruritus NRS score at Week 16 based on all observed values regardless of rescue treatment was reported.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

Pruritus NRS was an assessment tool used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, using an electronic questionnaire (e-diary). 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 \[0 = no itch; 10 = worst itch imaginable\]). Percent change from baseline in weekly average of daily peak pruritus NRS score at Week 16 based on observed values set to missing after rescue treatment was reported. Values after first rescue treatment were set to missing and participants with missing NRS score at Week 16 were counted as non-responders.

Time frame: Week 16

Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.~Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

The SCORAD index is a clinical tool for assessing the severity of atopic dermatitis (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). Due to study discontinuation, not all planned participants were enrolled. For those already enrolled, the study drug was discontinued and participants were transitioned to post-treatment follow-up period. A large amount of data remained uncollected as not all enrolled participants completed all planned study visits and procedures for assessments for some endpoints. Therefore, this endpoint was removed and no data was collected for this outcome measure.

Time frame: Week 16

Population: Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.

Serum Concentration of Functional Dupilumab was reported.

Time frame: Baseline (Week 0), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, and 36

Population: Data were reported for Dupilumab 300 gm Q2W and REGN3500 300 mg + Dupilumab 200 mg Q2W arms only. Pharmacokinetic (PK) analysis set included all randomized participants who received any study drug (active or placebo \[safety analysis set\]) and who had at least 1 non-missing study drug concentration result following the first dose of study drug. Here, Number Analyzed signifies those participants who were evaluable at given time points.

Serum Concentration of Functional REGN3500 was reported. Data was reported for REGN3500 300 mg Q2W and REGN3500 300 mg + Dupilumab 300 mg Q2W arms only

Time frame: Baseline (Week 0), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, and 36

Population: Pharmacokinetic (PK) analysis set included all randomized participants who received any study drug (active or placebo \[safety analysis set\]) and who had at least 1 non-missing study drug concentration result following the first dose of study drug. Here, Number Analyzed signifies those participants who were evaluable at given time points.

Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? Due to study discontinuation, not all planned participants were enrolled. For those already enrolled, the study drug was discontinued and participants were transitioned to post-treatment follow-up period. A large amount of data remained uncollected as not all enrolled participants completed all planned study visits and procedures for assessments for some endpoints. Therefore, this endpoint was removed and no data was collected for this outcome measure.

Time frame: Week 16

Population: Due to premature discontinuation, all statistical analyses were descriptive, and no hypothesis testing was performed.