NCT03738423

Efficacy, Safety, and Pharmacokinetic Profiles of REGN3500 Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis

Terminated Phase 2 Results posted Last updated 10 June 2022

What this trial tests

Phase 2 trial testing REGN3500 in Atopic Dermatitis in 129 participants. Terminated before completion.

Timeline

13 November 2018

Primary endpoint
13 March 2020

24 July 2020

Quick facts

Lead sponsor	Regeneron Pharmaceuticals
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	129
Start date	13 November 2018
Primary completion	13 March 2020
Estimated completion	24 July 2020
Sites	89 locations across Japan, United Kingdom, Germany, Hungary, Poland, South Korea, Canada, Australia

Drugs / interventions tested

• REGN3500 — full drug profile →
• REGN3500-Matching Placebo — full drug profile →

Conditions studied

• Atopic Dermatitis — all drugs for Atopic Dermatitis →

Sponsor

Regeneron Pharmaceuticals — full company profile →

Who can join

Adults 18 to 75, any sex, with Atopic Dermatitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · Week 16

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 was reported. Values after first rescue treatment were set to missing.

Group	Value	95% CI
Placebo Q2W	-33.5	± 41.81
REGN3500 30 mg Q8W	-57.9	± 31.65
REGN3500 100 mg Q4W	-52.7	± 46.64
REGN3500 300 mg Q4W	-80.0	± 10.54
REGN3500 300 mg Q2W	-54.0	± 36.80

Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score Based on All Observed Values Regardless of Rescue Treatment at Week 16 Primary · Week 16

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.

Group	Value	95% CI
Placebo Q2W	-18.9	± 52.01
REGN3500 30 mg Q8W	-46.0	± 45.35
REGN3500 100 mg Q4W	-48.7	± 44.66
REGN3500 300 mg Q4W	-67.0	± 28.74
REGN3500 300 mg Q2W	-56.1	± 35.32

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 Secondary · Week 16

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 reported. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.

Group	Value	95% CI
Placebo Q2W	30.0
REGN3500 30 mg Q8W	71.4
REGN3500 100 mg Q4W	71.4
REGN3500 300 mg Q4W	100
REGN3500 300 mg Q2W	55.6

Percentage of Participants Who Achieved Eczema Area and Severity Index-50 (EASI-50) (Greater Than or Equal to [≥] 50% Improvement From Baseline) Based on All Observed Values Regardless of Rescue Treatment at Week 16 Secondary · Week 16

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.

Group	Value	95% CI
Placebo Q2W	25.0
REGN3500 30 mg Q8W	60.0
REGN3500 100 mg Q4W	62.5
REGN3500 300 mg Q4W	77.8
REGN3500 300 mg Q2W	60.0

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 Secondary · Week 16

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

Group	Value	95% CI
Placebo Q2W	20.0
REGN3500 30 mg Q8W	28.6
REGN3500 100 mg Q4W	28.6
REGN3500 300 mg Q4W	71.4
REGN3500 300 mg Q2W	44.4

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 Secondary · Week 16

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.

Group	Value	95% CI
Placebo Q2W	16.7
REGN3500 30 mg Q8W	30.0
REGN3500 100 mg Q4W	25.0
REGN3500 300 mg Q4W	55.6
REGN3500 300 mg Q2W	40.0

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 Secondary · Week 16

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

Group	Value	95% CI
Placebo Q2W	10.0
REGN3500 30 mg Q8W	14.3
REGN3500 100 mg Q4W	28.6
REGN3500 300 mg Q4W	28.6
REGN3500 300 mg Q2W	33.3

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 Secondary · Week 16

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.

Group	Value	95% CI
Placebo Q2W	8.3
REGN3500 30 mg Q8W	20.0
REGN3500 100 mg Q4W	25.0
REGN3500 300 mg Q4W	22.2
REGN3500 300 mg Q2W	30.0

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 Secondary · Week 16

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 observed values set to missing after rescue treatment was reported.

Group	Value	95% CI
Placebo Q2W	-7.8	± 10.225
REGN3500 30 mg Q8W	-14.64	± 8.489
REGN3500 100 mg Q4W	-14.81	± 12.614
REGN3500 300 mg Q4W	-18.19	± 6.298
REGN3500 300 mg Q2W	-13.79	± 9.534

Absolute Change From Baseline in Eczema Area and Severity Index (EASI) Score Based on All Observed Values Regardless of Rescue Treatment at Week 16 Secondary · Week 16

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.

Group	Value	95% CI
Placebo Q2W	-4.10	± 13.079
REGN3500 30 mg Q8W	-12.07	± 11.764
REGN3500 100 mg Q4W	-13.83	± 12.000
REGN3500 300 mg Q4W	-15.15	± 8.299
REGN3500 300 mg Q2W	-14.68	± 9.410

Percentage of Participants With Both Investigator Global Assessment (IGA) Score 0 or 1 (on 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 Secondary · Week 16

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 a

Group	Value	95% CI
Placebo Q2W	10.0
REGN3500 30 mg Q8W	0.0
REGN3500 100 mg Q4W	28.6
REGN3500 300 mg Q4W	42.9
REGN3500 300 mg Q2W	33.3

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 Secondary · Week 16

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.

Group	Value	95% CI
Placebo Q2W	8.3
REGN3500 30 mg Q8W	0.0
REGN3500 100 mg Q4W	25.0
REGN3500 300 mg Q4W	33.3
REGN3500 300 mg Q2W	30.0

Adverse events — posted to ClinicalTrials.gov

Time frame: 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).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo Q2W

Serious: 0/25 (0%)

Deaths: 0/25

R3500 30 mg Q8W

Serious: 0/26 (0%)

Deaths: 0/26

R3500 100 mg Q4W

Serious: 0/26 (0%)

Deaths: 0/26

R3500 300 mg Q4W

Serious: 1/24 (4%)

Deaths: 0/24

R3500 300 mg Q2W

Serious: 2/26 (8%)

Deaths: 1/26

Serious adverse events (3 terms)

Reaction	System	Placebo Q2W	R3500 30 mg Q8W	R3500 100 mg Q4W	R3500 300 mg Q4W	R3500 300 mg Q2W
Gastroenteritis norovirus	Infections and infestations	—	—	—	—	—
Road traffic accident	Injury, poisoning and procedural complications	—	—	—	—	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	Placebo Q2W	R3500 30 mg Q8W	R3500 100 mg Q4W	R3500 300 mg Q4W	R3500 300 mg Q2W
Dermatitis atopic	Skin and subcutaneous tissue disorders	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—
Toothache	Gastrointestinal disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—

Most-reported serious reactions: Gastroenteritis norovirus, Road traffic accident, Breast cancer.

Data from ClinicalTrials.gov NCT03738423 adverse events section.

Sponsor's own description

The primary objective of the study is to assess the efficacy of REGN3500 monotherapy in Atopic dermatitis (AD), as well as understand the dose-response relationship, compared with placebo treatment, in adult patients with moderate-to-severe AD.

Secondary objectives are to:

* Assess the safety and tolerability of subcutaneous (SC) doses of REGN3500 monotherapy in adult patients with moderate-to-severe AD
* Assess the Pharmacokinetics (PK) of REGN3500 in adult patients with moderate-to-severe AD
* Assess the immunogenicity of REGN3500 in adult patients with moderate-to-severe AD

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Atopic dermatitis: an expanding therapeutic pipeline for a complex disease.
   Bieber T. · · 2022 · cited 421× · PMID 34417579 · DOI 10.1038/s41573-021-00266-6
2. The translational revolution in atopic dermatitis: the paradigm shift from pathogenesis to treatment.
   Facheris P, Jeffery J, Del Duca E, Guttman-Yassky E. · · 2023 · cited 150× · PMID 36928371 · DOI 10.1038/s41423-023-00992-4
3. T cell pathology in skin inflammation.
   Sabat R, Wolk K, Loyal L, Döcke WD, et al · · 2019 · cited 134× · PMID 31028434 · DOI 10.1007/s00281-019-00742-7
4. Research Techniques Made Simple: Mouse Models of Atopic Dermatitis.
   Kim D, Kobayashi T, Nagao K. · · 2019 · cited 73× · PMID 31010529 · DOI 10.1016/j.jid.2019.02.014
5. IL33 and Mast Cells-The Key Regulators of Immune Responses in Gastrointestinal Cancers?
   Eissmann MF, Buchert M, Ernst M. · · 2020 · cited 31× · PMID 32719677 · DOI 10.3389/fimmu.2020.01389
6. Unraveling Atopic Dermatitis: Insights into Pathophysiology, Therapeutic Advances, and Future Perspectives.
   Pareek A, Kumari L, Pareek A, Chaudhary S, et al · · 2024 · cited 27× · PMID 38474389 · DOI 10.3390/cells13050425
7. Targeting the Epithelium-Derived Innate Cytokines: From Bench to Bedside.
   Ham J, Shin JW, Ko BC, Kim HY. · · 2022 · cited 21× · PMID 35291657 · DOI 10.4110/in.2022.22.e11
8. A Systematic Review of Atopic Dermatitis: The Intriguing Journey Starting from Physiopathology to Treatment, from Laboratory Bench to Bedside.
   Radi G, Campanti A, Diotallevi F, Martina E, et al · · 2022 · cited 17× · PMID 36359220 · DOI 10.3390/biomedicines10112700