NCT02395133

A Study to Confirm the Efficacy and Safety of Different Dupilumab Dose Regimens in Adults With Atopic Dermatitis (AD)

Completed Phase 3 Results posted

What this trial tests

Phase 3 trial testing Dupilumab in Atopic Dermatitis in 422 participants. Completed in 18 October 2016.

Timeline

25 March 2015

18 October 2016

Quick facts

Lead sponsor	Regeneron Pharmaceuticals
Phase	Phase 3
Status	Completed
Enrollment	422
Start date	25 March 2015
Estimated completion	18 October 2016

Drugs / interventions tested

• Dupilumab (DUPILUMAB) — full drug profile →
• Placebo

Conditions studied

• Atopic Dermatitis — all drugs for Atopic Dermatitis →

Sponsor

Regeneron Pharmaceuticals — full company profile →

Who can join

Eligibility, any sex, with Atopic Dermatitis.

Results — posted to ClinicalTrials.gov

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

Difference Between Current Study Baseline and Week 36 in Percent Change in EASI From Parent Study Baseline (NCT02277743 and NCT02277769) Primary · Baseline (Parent Study), Baseline (Current Study) and Week 36 (Current study)

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Difference of percent change in EASI between current study baseline and week 36 in from parent study baseline (NCT02277743 and NCT02277769) was reported. Values after first rescue treatment used were set to missing before multiple imputation (MI).

Group	Value	95% CI
Placebo QW	21.67	± 3.134
Dupilumab 300 mg Q8W	6.84	± 2.434
Dupilumab 300 mg Q4W	3.84	± 2.283
Dupilumab 300 mg Q2W/QW	0.06	± 1.736

Percentage of Participants With Eczema Area and Severity Index >= 75% [EASI-75] at Baseline of Current Study Maintaining EASI-75 at Week 36 Primary · Week 36

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved \>=75% overall improvement in EASI score at Week 36. Values after first rescue treatment used were set to missing. Patients with missing value at week 36 were considered as a non-responder.

Group	Value	95% CI
Placebo QW	30.4
Dupilumab 300 mg Q8W	54.9
Dupilumab 300 mg Q4W	58.3
Dupilumab 300 mg Q2W/QW	71.6

Percentage of Participants Maintaining Investigator Global Assessment (IGA) Response Within 1 Point of Baseline at Week 36 Secondary · Baseline, Week 36

IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score of 0 or 1 at baseline and maintaining within 1 point of baseline were reported as responders. Values after first rescue treatment used were set to missing. Participants with missing value at a visit were considered as a non-responder.

Group	Value	95% CI
Placebo QW	28.6
Dupilumab 300 mg Q8W	50.0
Dupilumab 300 mg Q4W	62.1
Dupilumab 300 mg Q2W/QW	70.6

Percentage of Participants Maintaining Investigator Global Assessment (IGA) Response at 0 or 1 Point at Week 36 Secondary · Week 36

IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score of 0 or 1 at week 36 were reported as responders. Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 36 were considered as non-responders.

Group	Value	95% CI
Placebo QW	14.3
Dupilumab 300 mg Q8W	32.8
Dupilumab 300 mg Q4W	43.9
Dupilumab 300 mg Q2W/QW	54.0

Percentage of Participants With Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score Increased by 3 or More Points From Baseline to Week 35 Secondary · Baseline up to Week 35

Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 35 were considered as non-responders.

Group	Value	95% CI
Placebo QW	70.0
Dupilumab 300 mg Q8W	55.6
Dupilumab 300 mg Q4W	49.4
Dupilumab 300 mg Q2W/QW	33.9

Time to First Event of Investigator's Global Assessment (IGA) >= 2 for Participants With IGA 0 or 1 at Baseline Secondary · Baseline up to Week 36

IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear).

Group	Value	95% CI
Placebo QW	57	56 – 58
Dupilumab 300 mg Q8W	85	59 – 113
Dupilumab 300 mg Q4W	80	55 – 85
Dupilumab 300 mg Q2W/QW	114	85 – 169

Percentage of Participants With Increased Investigator's Global Assessment (IGA) Score 3 or 4 at Week 36 Secondary · Week 36

IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 36 were considered as responders (i.e. having a increase 3 or 4 of IGA value).

Group	Value	95% CI
Placebo QW	66.7
Dupilumab 300 mg Q8W	48.4
Dupilumab 300 mg Q4W	34.8
Dupilumab 300 mg Q2W/QW	26.2

Percentage of Participants With Eczema Area and Severity Index-50 (EASI-50) (>= 50% Reduction in EASI Score) at Week 36 Secondary · Week 36

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved \>= 50% overall improvement in EASI score from baseline to Week 36. Values after first rescue treatment were set to missing and participants with missing EASI-50 scores at Week 36 were considered as non-res

Group	Value	95% CI
Placebo QW	39.8
Dupilumab 300 mg Q8W	54.8
Dupilumab 300 mg Q4W	60.5
Dupilumab 300 mg Q2W/QW	73.4

Absolute Change From Baseline in Eczema Area and Severity Index (EASI) at Week 36 Secondary · Baseline, Week 36

The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Values after first rescue treatment were set to missing and participants with missing Values at Week 36 were imputed by using multiple imputation method.

Group	Value	95% CI
Placebo QW	6.61	± 0.799
Dupilumab 300 mg Q8W	1.75	± 0.738
Dupilumab 300 mg Q4W	1.37	± 0.735
Dupilumab 300 mg Q2W/QW	0.09	± 0.511

Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 36 Secondary · Baseline, Week 36

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

Group	Value	95% CI
Placebo QW	18.61	± 2.107
Dupilumab 300 mg Q8W	6.62	± 2.010
Dupilumab 300 mg Q4W	2.25	± 1.899
Dupilumab 300 mg Q2W/QW	0.99	± 1.350

Absolute Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score at Week 35 Secondary · Baseline, Week 35

Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Values after first rescue treatment used were set to missing before MI.

Group	Value	95% CI
Placebo QW	2.5	± 0.29
Dupilumab 300 mg Q8W	1.1	± 0.27
Dupilumab 300 mg Q4W	0.6	± 0.25
Dupilumab 300 mg Q2W/QW	-0.1	± 0.20

Absolute Change From Baseline in Body Surface Area (BSA) Through Week 36 Secondary · Baseline through Week 36

BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]). It was reported as a percentage of all major body sections combined. Values after first rescue treatment used were set to missing (censoring) before MI.

Group	Value	95% CI
Placebo QW	9.16	± 1.642
Dupilumab 300 mg Q8W	2.74	± 1.530
Dupilumab 300 mg Q4W	1.74	± 1.457
Dupilumab 300 mg Q2W/QW	-1.27	± 1.044

Adverse events — posted to ClinicalTrials.gov

Time frame: All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 36) regardless of seriousness or relationship to investigational product.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo QW

Serious: 1/82 (1%)

Deaths: 0/82

Dupilumab 300 mg Q8W

Serious: 3/84 (4%)

Deaths: 0/84

Dupilumab 300 mg Q4W

Serious: 4/87 (5%)

Deaths: 1/87

Dupilumab 300 mg Q2W/QW

Serious: 6/167 (4%)

Deaths: 0/167

Serious adverse events (18 terms)

Reaction	System	Placebo QW	Dupilumab 300 mg Q8W	Dupilumab 300 mg Q4W	Dupilumab 300 mg Q2W/QW
Road traffic accident	Injury, poisoning and procedural complications	—	—	—	—
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—
Tachycardia induced cardiomyopathy	Cardiac disorders	—	—	—	—
Anaphylactic reaction	Immune system disorders	—	—	—	—
Gun shot wound	Injury, poisoning and procedural complications	—	—	—	—
Muscle injury	Injury, poisoning and procedural complications	—	—	—	—
Open fracture	Injury, poisoning and procedural complications	—	—	—	—
Glioblastoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Biochemical pregnancy	Pregnancy, puerperium and perinatal conditions	—	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Dermatitis atopic	Skin and subcutaneous tissue disorders	—	—	—	—
Abortion induced	Surgical and medical procedures	—	—	—	—
Deep vein thrombosis	Vascular disorders	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—
Ligament Rupture	Injury, poisoning and procedural complications	—	—	—	—
Wound Dehiscence	Injury, poisoning and procedural complications	—	—	—	—

Other adverse events (8 terms — click to expand)

Reaction	System	Placebo QW	Dupilumab 300 mg Q8W	Dupilumab 300 mg Q4W	Dupilumab 300 mg Q2W/QW
Dermatitis atopic	Skin and subcutaneous tissue disorders	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Injection site reaction	General disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—
Influenza	Infections and infestations	—	—	—	—
Oral herpes	Infections and infestations	—	—	—	—

Most-reported serious reactions: Road traffic accident, Basal cell carcinoma, Atrial fibrillation, Tachycardia induced cardiomyopathy, Anaphylactic reaction, Gun shot wound, Muscle injury, Open fracture.

Data from ClinicalTrials.gov NCT02395133 adverse events section.

Publications & conference data

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

1. Conjunctivitis in dupilumab clinical trials.
   Akinlade B, Guttman-Yassky E, de Bruin-Weller M, Simpson EL, et al · · 2019 · cited 303× · PMID 30851191 · DOI 10.1111/bjd.17869
2. Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis: A Randomized Clinical Trial.
   Worm M, Simpson EL, Thaçi D, Bissonnette R, et al · · 2020 · cited 160× · PMID 31876900 · DOI 10.1001/jamadermatol.2019.3617
3. Antibodies to watch in 2016.
   Reichert JM. · · 2016 · cited 135× · PMID 26651519 · DOI 10.1080/19420862.2015.1125583
4. Dupilumab Provides Favorable Safety and Sustained Efficacy for up to 3 Years in an Open-Label Study of Adults with Moderate-to-Severe Atopic Dermatitis.
   Beck LA, Thaçi D, Deleuran M, Blauvelt A, et al · · 2020 · cited 94× · PMID 32557382 · DOI 10.1007/s40257-020-00527-x
5. Patient-Reported Outcome Measures in Atopic Dermatitis and Chronic Hand Eczema in Adults.
   Barrett A, Hahn-Pedersen J, Kragh N, Evans E, et al · · 2019 · cited 56× · PMID 31270775 · DOI 10.1007/s40271-019-00373-y
6. Biologic Versus Small Molecule Therapy for Treating Moderate to Severe Atopic Dermatitis: Clinical Considerations.
   Butala S, Castelo-Soccio L, Seshadri R, Simpson EL, et al · · 2023 · cited 42× · PMID 36948491 · DOI 10.1016/j.jaip.2023.03.011
7. Dupilumab: an evidence-based review of its potential in the treatment of atopic dermatitis.
   Eshtiaghi P, Gooderham MJ. · · 2018 · cited 36× · PMID 29503598 · DOI 10.2147/ce.s133661
8. Systemic treatments for eczema: a network meta-analysis.
   Sawangjit R, Dilokthornsakul P, Lloyd-Lavery A, Lai NM, et al · · 2020 · cited 30× · PMID 32927498 · DOI 10.1002/14651858.cd013206.pub2