Trial Outcomes & Findings for Efficacy and Safety of REGN3500 Monotherapy and Combination of REGN3500 Plus Dupilumab in Adult Patients With Moderate-to-Severe Atopic Dermatitis (NCT NCT03736967)

NCT ID: NCT03736967

Last Updated: 2021-11-01

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 206 participants
• Primary outcome timeframe: Week 16
• Results posted on: 2021-11-01

Participant Flow

A total of 299 participants were screened at sites in Republic of Korea, United States of America, Germany, Poland, Czech Republic, Belgium and Spain. Out of 299 participants, 206 participants met eligibility criteria and randomized in this study.

Participants were randomized in a 1:1:1:1 ratio to 1 of the 4 treatment groups: Placebo every 2 weeks (Q2W); REGN3500 300 milligrams (mg) Q2W; Dupilumab 300 mg Q2W and combination of REGN3500 300 mg and Dupilumab 300 mg Q2W.

Participant milestones

Measure	Placebo Q2W Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Overall Study STARTED	51	52	51	52
Overall Study Treated	50	52	51	52
Overall Study COMPLETED	20	24	27	22
Overall Study NOT COMPLETED	31	28	24	30

Reasons for withdrawal

Measure	Placebo Q2W Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Overall Study Withdrawal by Subject	26	25	23	26
Overall Study Lost to Follow-up	3	2	1	1
Overall Study Physician Decision	1	0	0	1
Overall Study Adverse Event	0	1	0	1
Overall Study Death	0	0	0	1
Overall Study Randomized but never treated	1	0	0	0

Baseline Characteristics

FAS includes all randomized participants and was based on the treatment allocated (as randomized). Here, "Number of Participants Analyzed" signifies those participants who were evaluable at baseline.

Baseline characteristics by cohort

Measure	Placebo Q2W n=51 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=52 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=51 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=52 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.	Total n=206 Participants Total of all reporting groups
Age, Continuous	34.9 Years STANDARD_DEVIATION 14.04 • n=51 Participants	33.3 Years STANDARD_DEVIATION 12.19 • n=52 Participants	38.4 Years STANDARD_DEVIATION 15.89 • n=51 Participants	32.1 Years STANDARD_DEVIATION 12.10 • n=52 Participants	34.7 Years STANDARD_DEVIATION 13.74 • n=206 Participants
Sex: Female, Male Female	19 Participants n=51 Participants	16 Participants n=52 Participants	23 Participants n=51 Participants	22 Participants n=52 Participants	80 Participants n=206 Participants
Sex: Female, Male Male	32 Participants n=51 Participants	36 Participants n=52 Participants	28 Participants n=51 Participants	30 Participants n=52 Participants	126 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=51 Participants	2 Participants n=52 Participants	1 Participants n=51 Participants	1 Participants n=52 Participants	4 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	51 Participants n=51 Participants	48 Participants n=52 Participants	50 Participants n=51 Participants	50 Participants n=52 Participants	199 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=51 Participants	2 Participants n=52 Participants	0 Participants n=51 Participants	1 Participants n=52 Participants	3 Participants n=206 Participants
Race/Ethnicity, Customized White	26 Participants n=51 Participants	29 Participants n=52 Participants	38 Participants n=51 Participants	31 Participants n=52 Participants	124 Participants n=206 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=51 Participants	6 Participants n=52 Participants	3 Participants n=51 Participants	2 Participants n=52 Participants	12 Participants n=206 Participants
Race/Ethnicity, Customized Asian	24 Participants n=51 Participants	16 Participants n=52 Participants	10 Participants n=51 Participants	19 Participants n=52 Participants	69 Participants n=206 Participants
Race/Ethnicity, Customized Other	0 Participants n=51 Participants	1 Participants n=52 Participants	0 Participants n=51 Participants	0 Participants n=52 Participants	1 Participants n=206 Participants
Eczema Area and Severity Index (EASI) Score	28.2 Scores on a Scale STANDARD_DEVIATION 9.54 • n=50 Participants • FAS includes all randomized participants and was based on the treatment allocated (as randomized). Here, "Number of Participants Analyzed" signifies those participants who were evaluable at baseline.	29.9 Scores on a Scale STANDARD_DEVIATION 13.02 • n=52 Participants • FAS includes all randomized participants and was based on the treatment allocated (as randomized). Here, "Number of Participants Analyzed" signifies those participants who were evaluable at baseline.	30.6 Scores on a Scale STANDARD_DEVIATION 13.86 • n=51 Participants • FAS includes all randomized participants and was based on the treatment allocated (as randomized). Here, "Number of Participants Analyzed" signifies those participants who were evaluable at baseline.	29.0 Scores on a Scale STANDARD_DEVIATION 10.74 • n=52 Participants • FAS includes all randomized participants and was based on the treatment allocated (as randomized). Here, "Number of Participants Analyzed" signifies those participants who were evaluable at baseline.	29.4 Scores on a Scale STANDARD_DEVIATION 11.87 • n=205 Participants • FAS includes all randomized participants and was based on the treatment allocated (as randomized). Here, "Number of Participants Analyzed" signifies those participants who were evaluable at baseline.

PRIMARY outcome

Timeframe: 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 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.

Outcome measures

Measure	Placebo Q2W n=19 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=14 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=22 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=20 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score Based on Observed Values Set to Missing After Rescue Treatment at Week 16	-52.4 Percentage of Change Standard Deviation 31.86	-66.6 Percentage of Change Standard Deviation 22.46	-77.8 Percentage of Change Standard Deviation 23.73	-76.9 Percentage of Change Standard Deviation 20.79

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=23 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=23 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=26 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=24 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score Based on All Observed Values Regardless of Rescue Treatment at Week 16	-46.6 Percentage of Change Standard Deviation 36.58	-58.0 Percentage of Change Standard Deviation 29.69	-77.4 Percentage of Change Standard Deviation 22.59	-75.8 Percentage of Change Standard Deviation 19.66

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=19 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=14 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=22 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=20 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Percentage of Participants Who Achieved Eczema Area and Severity Index-50 (EASI-50) (Greater Than or Equal to [≥] 50 Percent [%] Improvement From Baseline) Based on Observed Values Set to Missing After Rescue Treatment at Week 16	57.9 Percentage of Participants	78.6 Percentage of Participants	95.5 Percentage of Participants	85.0 Percentage of Participants

SECONDARY outcome

Timeframe: 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 were based on all observed values regardless of rescue treatment were reported.

Outcome measures

Measure	Placebo Q2W n=23 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=23 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=26 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=24 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Percentage of Participants Who Achieved Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) Based on All Observed Values Regardless of Rescue Treatment at Week 16	52.2 Percentage of Participants	65.2 Percentage of Participants	96.2 Percentage of Participants	87.5 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=19 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=14 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=22 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=20 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Percentage of Participants Who Achieved Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) Based on Observed Values Set to Missing After Rescue Treatment at Week 16	31.6 Percentage of Participants	35.7 Percentage of Participants	63.6 Percentage of Participants	60.0 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=23 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=23 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=26 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=24 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Percentage of Participants Who Achieved Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) Based on All Observed Values Regardless of Rescue Treatment at Week 16	26.1 Percentage of Participants	30.4 Percentage of Participants	61.5 Percentage of Participants	58.3 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=19 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=14 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=22 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=20 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Percentage of Participants Who Achieved Eczema Area and Severity Index-90 (EASI-90) (≥90% Improvement From Baseline) Based on Observed Values Set to Missing After Rescue Treatment at Week 16	10.5 Percentage of Participants	28.6 Percentage of Participants	40.9 Percentage of Participants	35.0 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=23 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=23 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=26 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=24 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Percentage of Participants Who Achieved Eczema Area and Severity Index-90 (EASI-90) (≥90% Improvement From Baseline) Based on All Observed Values Regardless of Rescue Treatment at Week 16	8.7 Percentage of Participants	17.4 Percentage of Participants	38.5 Percentage of Participants	29.2 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=19 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=14 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=22 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=20 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Absolute Change From Baseline in Eczema Area and Severity Index (EASI) Score Based on Observed Values Set to Missing After Rescue Treatment at Week 16	-13.25 Scores on a Scale Standard Deviation 8.073	-18.94 Scores on a Scale Standard Deviation 9.383	-25.40 Scores on a Scale Standard Deviation 15.769	-23.28 Scores on a Scale Standard Deviation 9.177

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=23 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=23 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=26 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=24 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Absolute Change From Baseline in Eczema Area and Severity Index (EASI) Score Based on All Observed Values Regardless of Rescue Treatment at Week 16	-12.18 Scores on a Scale Standard Deviation 9.819	-16.46 Scores on a Scale Standard Deviation 10.002	-24.06 Scores on a Scale Standard Deviation 14.825	-21.82 Scores on a Scale Standard Deviation 9.008

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=19 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=14 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=22 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=20 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Percentage of Participants With Both Investigator Global Assessment (IGA) Score 0 or 1 (on the 0 to 5 IGA Scale) and a Reduction From Baseline of ≥2 Points Based on Observed Values Set to Missing After Rescue Treatment at Week 16	21.1 Percentage of Participants	28.6 Percentage of Participants	36.4 Percentage of Participants	35.0 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=23 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=23 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=26 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=24 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Percentage of Participants With Both IGA Score 0 or 1 (on the 0 to 5 IGA Scale) and a Reduction From Baseline of ≥2 Points Based on All Observed Values Regardless of Rescue Treatment at Week 16	17.4 Percentage of Participants	21.7 Percentage of Participants	38.5 Percentage of Participants	29.2 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=15 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=12 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=17 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=14 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Absolute Change From Baseline in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score Based on Observed Values Set to Missing After Rescue Treatment at Week 16	-2.08 Scores on a Scale Standard Deviation 2.825	-2.90 Scores on a Scale Standard Deviation 1.781	-3.16 Scores on a Scale Standard Deviation 2.607	-3.92 Scores on a Scale Standard Deviation 2.433

SECONDARY outcome

Timeframe: 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 all observed values regardless of rescue treatment was reported.

Outcome measures

Measure	Placebo Q2W n=18 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=15 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=18 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=17 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Absolute Change From Baseline in Weekly Average of Daily Peak Pruritus NRS Score Based on All Observed Values Regardless of Rescue Treatment at Week 16	-2.11 Scores on a Scale Standard Deviation 2.651	-2.87 Scores on a Scale Standard Deviation 1.743	-3.19 Scores on a Scale Standard Deviation 2.532	-3.64 Scores on a Scale Standard Deviation 2.326

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=15 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=12 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=17 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=14 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Percent Change From Baseline in in Weekly Average of Daily Peak Pruritus NRS Score Based on Observed Values Set to Missing After Rescue Treatment at Week 16	-26.6 Percentage of Change Standard Deviation 36.71	-38.0 Percentage of Change Standard Deviation 22.94	-44.9 Percentage of Change Standard Deviation 35.73	-60.2 Percentage of Change Standard Deviation 34.87

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=18 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=15 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=18 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=17 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Percent Change From Baseline in in Weekly Average of Daily Peak Pruritus NRS Score Based on All Observed Values Regardless of Rescue Treatment at Week 16	-27.6 Percentage of Change Standard Deviation 35.04	-37.8 Percentage of Change Standard Deviation 21.88	-45.1 Percentage of Change Standard Deviation 34.68	-55.7 Percentage of Change Standard Deviation 34.22

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=15 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=12 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=17 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=14 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Percentage of Participants With Improvement (Reduction From Baseline) in Weekly Average of Peak Daily Pruritus NRS ≥4 Based on Observed Values Set to Missing After Rescue Treatment at Week 16	26.7 Percentage of Participants	16.7 Percentage of Participants	35.3 Percentage of Participants	50.0 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo Q2W n=18 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=15 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=18 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=17 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Percentage of Participants With Improvement (Reduction From Baseline) in Weekly Average of Peak Daily Pruritus NRS ≥4 Based on All Observed Values Regardless of Rescue Treatment at Week 16	27.8 Percentage of Participants	20.0 Percentage of Participants	33.3 Percentage of Participants	41.2 Percentage of Participants

SECONDARY outcome

Timeframe: Week 16

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 16

Population: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 16

Population: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Measure	Placebo Q2W n=50 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=52 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=51 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=52 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) From Baseline up to Week 16 Participants with TEAEs	25 Participants	24 Participants	29 Participants	22 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) From Baseline up to Week 16 Participants with Serious TEAEs	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) From Baseline up to Week 16 Participants with AESIs	2 Participants	0 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Measure	Placebo Q2W n=50 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=52 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=51 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=52 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) From Baseline up to Week 36 Participants with TEAEs	27 Participants	26 Participants	35 Participants	28 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) From Baseline up to Week 36 Participants with Serious TEAEs	1 Participants	1 Participants	2 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs) From Baseline up to Week 36 Participants with AESIs	2 Participants	0 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo Q2W n=43 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=48 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=44 Participants Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W n=46 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Number of Participants With Positive Treatment-Emergent Anti-drug Antibodies (ADA) to REGN3500 and Dupilumab	0 Participants	0 Participants	3 Participants	6 Participants

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Placebo Q2W n=52 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=52 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Serum Concentration of Functional REGN3500 Week 28	7.31 Milligrams per Liter (mg/L) Standard Deviation 5.49	12.3 Milligrams per Liter (mg/L) Standard Deviation 12.5	—	—
Serum Concentration of Functional REGN3500 Week 32	4.61 Milligrams per Liter (mg/L) Standard Deviation 4.48	5.43 Milligrams per Liter (mg/L) Standard Deviation 4.12	—	—
Serum Concentration of Functional REGN3500 Week 0	0 Milligrams per Liter (mg/L) Standard Deviation 0	0.00373 Milligrams per Liter (mg/L) Standard Deviation 0.0269	—	—
Serum Concentration of Functional REGN3500 Week 2	22.8 Milligrams per Liter (mg/L) Standard Deviation 9.06	25.2 Milligrams per Liter (mg/L) Standard Deviation 9.58	—	—
Serum Concentration of Functional REGN3500 Week 4	41.6 Milligrams per Liter (mg/L) Standard Deviation 14.8	41.9 Milligrams per Liter (mg/L) Standard Deviation 16.4	—	—
Serum Concentration of Functional REGN3500 Week 8	58.8 Milligrams per Liter (mg/L) Standard Deviation 20.5	63.0 Milligrams per Liter (mg/L) Standard Deviation 22.8	—	—
Serum Concentration of Functional REGN3500 Week 12	67.4 Milligrams per Liter (mg/L) Standard Deviation 26.7	74.5 Milligrams per Liter (mg/L) Standard Deviation 25.7	—	—
Serum Concentration of Functional REGN3500 Week 16	73.9 Milligrams per Liter (mg/L) Standard Deviation 31.4	82.4 Milligrams per Liter (mg/L) Standard Deviation 33.5	—	—
Serum Concentration of Functional REGN3500 Week 20	33.3 Milligrams per Liter (mg/L) Standard Deviation 21.9	45.1 Milligrams per Liter (mg/L) Standard Deviation 24.2	—	—
Serum Concentration of Functional REGN3500 Week 24	13.1 Milligrams per Liter (mg/L) Standard Deviation 11.9	23.3 Milligrams per Liter (mg/L) Standard Deviation 14.4	—	—
Serum Concentration of Functional REGN3500 Week 36	2.42 Milligrams per Liter (mg/L) Standard Deviation 2.70	2.79 Milligrams per Liter (mg/L) Standard Deviation 2.48	—	—

SECONDARY outcome

Timeframe: 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 Dupilumab was reported.

Outcome measures

Measure	Placebo Q2W n=51 Participants Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	REGN3500 300 mg Q2W n=52 Participants Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	REGN3500 300 mg + Dupilumab 300 mg Q2W Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Serum Concentration of Functional Dupilumab Week 0	0 mg/L Standard Deviation 0	0.00219 mg/L Standard Deviation 0.0158	—	—
Serum Concentration of Functional Dupilumab Week 2	51.4 mg/L Standard Deviation 19.0	50.6 mg/L Standard Deviation 19.0	—	—
Serum Concentration of Functional Dupilumab Week 4	51.5 mg/L Standard Deviation 23.6	57.6 mg/L Standard Deviation 26.1	—	—
Serum Concentration of Functional Dupilumab Week 8	63.0 mg/L Standard Deviation 32.5	64.9 mg/L Standard Deviation 26.3	—	—
Serum Concentration of Functional Dupilumab Week 12	70.4 mg/L Standard Deviation 37.8	69.6 mg/L Standard Deviation 29.2	—	—
Serum Concentration of Functional Dupilumab Week 16	73.4 mg/L Standard Deviation 39.2	71.6 mg/L Standard Deviation 30.9	—	—
Serum Concentration of Functional Dupilumab Week 20	25.8 mg/L Standard Deviation 26.9	28.0 mg/L Standard Deviation 24.8	—	—
Serum Concentration of Functional Dupilumab Week 24	4.36 mg/L Standard Deviation 8.97	6.50 mg/L Standard Deviation 12.5	—	—
Serum Concentration of Functional Dupilumab Week 28	1.47 mg/L Standard Deviation 3.86	2.39 mg/L Standard Deviation 7.93	—	—
Serum Concentration of Functional Dupilumab Week 32	0.0227 mg/L Standard Deviation 0.0850	0 mg/L Standard Deviation 0	—	—
Serum Concentration of Functional Dupilumab Week 36	0 mg/L Standard Deviation 0	0 mg/L Standard Deviation 0	—	—

Adverse Events

Placebo Q2W

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

R3500 300 mg Q2W

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Dupilumab 300 mg Q2W

Serious events: 2 serious events

Other events: 25 other events

Deaths: 0 deaths

R3500 300 mg and Dupilumab 300 mg Q2W

Serious events: 1 serious events

Other events: 20 other events

Deaths: 1 deaths

Serious adverse events

Measure	Placebo Q2W n=50 participants at risk Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	R3500 300 mg Q2W n=52 participants at risk Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=51 participants at risk Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	R3500 300 mg and Dupilumab 300 mg Q2W n=52 participants at risk Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Infections and infestations Sepsis	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/51 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	1.9% 1/52 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Infections and infestations Tracheobronchitis	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	1.9% 1/52 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/51 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Renal and urinary disorders Goodpasture's syndrome	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/51 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	1.9% 1/52 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Immune system disorders Hypersensitivity	2.0% 1/50 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/51 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Nervous system disorders Cerebrovascular accident	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	1.9% 1/52 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/51 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Nervous system disorders Encephalopathy	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	1.9% 1/52 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/51 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Nervous system disorders Intracranial aneurysm	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	2.0% 1/51 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Nervous system disorders Ruptured cerebral aneurysm	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	2.0% 1/51 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	1.9% 1/52 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/51 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).

Other adverse events

Measure	Placebo Q2W n=50 participants at risk Participants received 2 subcutaneous (SC) injections of placebo matched to REGN3500 and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of placebo matched to REGN3500 and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	R3500 300 mg Q2W n=52 participants at risk Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of placebo matched to Dupilumab (loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 1 SC injection of placebo matched to Dupilumab Q2W up to Week 14.	Dupilumab 300 mg Q2W n=51 participants at risk Participants received 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) and 2 SC injections of placebo matched to REGN3500 on Day 1 and then 1 SC injection of Dupilumab at a dose 300 mg and 2 SC injections of placebo matched to REGN3500 Q2W up to Week 14.	R3500 300 mg and Dupilumab 300 mg Q2W n=52 participants at risk Participants received 2 SC injections of REGN3500 at a dose of 150 mg (300 mg loading dose) and 2 SC injections of Dupilumab at a dose of 300 mg (600 mg loading dose) on Day 1 and then 2 SC injections of REGN3500 at a dose of 150 mg and 1 SC injection of Dupilumab at a dose of 300 mg Q2W up to Week 14.
Infections and infestations Nasopharyngitis	16.0% 8/50 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	9.6% 5/52 • Number of events 5 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	21.6% 11/51 • Number of events 14 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	11.5% 6/52 • Number of events 6 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Infections and infestations Upper respiratory tract infection	2.0% 1/50 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	3.9% 2/51 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	5.8% 3/52 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Infections and infestations Conjunctivitis	2.0% 1/50 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	11.8% 6/51 • Number of events 6 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	1.9% 1/52 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Infections and infestations Oral herpes	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	7.8% 4/51 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	1.9% 1/52 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Infections and infestations Urinary tract infection	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	5.8% 3/52 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	2.0% 1/51 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	0.00% 0/52 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Skin and subcutaneous tissue disorders Dermatitis atopic	14.0% 7/50 • Number of events 9 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	13.5% 7/52 • Number of events 8 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	15.7% 8/51 • Number of events 11 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	19.2% 10/52 • Number of events 11 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Eye disorders Conjunctivitis allergic	0.00% 0/50 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	1.9% 1/52 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	3.9% 2/51 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	5.8% 3/52 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Nervous system disorders Headache	4.0% 2/50 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	1.9% 1/52 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	5.9% 3/51 • Number of events 4 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	1.9% 1/52 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	4.0% 2/50 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	1.9% 1/52 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	5.9% 3/51 • Number of events 3 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).	1.9% 1/52 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the end of study (Week 36) regardless of seriousness or relationship to investigational product (IP).

Additional Information

Clinical Trials Administrator

Regeneron Pharmaceuticals, Inc.

Phone: 844-734-6643

Email: clinicaltrials@regeneron.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
• Publication restrictions are in place

Restriction type: OTHER