Safety and Tolerability of Dupilumab in Participants With Moderate to Severe Atopic Dermatitis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety and tolerability of repeated subcutaneous (SC) doses of Dupilumab in participants with moderate-to-severe atopic dermatitis (AD).

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Sequential Ascending, Repeated-Dose Study of the Safety, Tolerability, and Pharmacokinetics of Subcutaneous REGN668 in Patients With Moderate-to-Severe Atopic Dermatitis

Conditions
-----------------
Atopic Dermatitis

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Dupilumab
* Other: Background treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, 18 years or older; Chronic AD diagnosed by the Eichenfield revised criteria of Hannifin and Rajka that had been present for at least 3 years before the screening visit; Eczema Area and Severity Index (EASI) score ≥ 12 at the screening and baseline visits; Investigator's Global Assessment (IGA) score ≥ 3 at the screening and baseline visits; ≥ 10% body surface area (BSA) of AD involvement at the screening and baseline visits; History of inadequate response to a stable (≥ 1 month) regimen of topical corticosteroids or calcineurin inhibitors as treatment for AD within 3 months before the screening visit. Exclusion Criteria: Positive Hepatitis B surface antigen, and/or positive Hepatitis C antibody at the screening visit; Treatment with an investigational drug within 8 weeks or within 5 half-lives, if known, whichever is longer, before the baseline visit; Treatment with leukotriene inhibitors within 4 weeks before the baseline visit; Treatment with systemic corticosteroids within 4 weeks before the baseline visit; Treatment with topical corticosteroids, tacrolimus, and/or pimecrolimus within 1 week before the baseline visit; Systemic treatment for AD with an immunosuppressive/immunomodulating substance within 4 weeks before the baseline visit; Chronic or acute infection requiring treatment with oral or IV antibiotics, antivirals, or antifungals within 4 weeks before the screening visit or superficial skin infections within 1 week before the screening visit; Known history of human immunodeficiency virus (HIV) infection; History of clinical parasite infection, other than treated trichomoniasis; History of malignancy within 5 years before the baseline visit, with the following exceptions: participants with a history of completely treated carcinoma in-situ of cervix, and non-metastatic squamous or basal cell carcinoma of the skin were allowed; Any medical or psychiatric condition which, in the opinion of the investigator or the sponsor's medical monitor, would place the participant at risk, interfere with participation in the study, or interfere with the interpretation of study results; Pregnant or breast-feeding women; Unwilling to use adequate birth control, if of reproductive potential and sexually active.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo<br>Placebo (for Dupilumab) as a single subcutaneous (SC) injection on Day 1, 8, 15, and 22 | Drug: Placebo<br>* A total of 4 doses were administered.<br>Other: Background treatment<br>* Participants were required to apply stable doses of an additive-free, basic bland emollient on the affected areas of the skin twice daily throughout the study.<br>|
| Experimental: Dupilumab 150 mg<br>Dupilumab 150 mg as a single SC injection on Day 1, 8, 15, and 22 | Drug: Dupilumab<br>* A total of 4 doses were administered.<br>* Other names: Dupixent;Other: Background treatment<br>* Participants were required to apply stable doses of an additive-free, basic bland emollient on the affected areas of the skin twice daily throughout the study.<br>|
| Experimental: Dupilumab 300 mg<br>Dupilumab 300 mg as a single SC injection on Day 1, 8, 15, and 22 | Drug: Dupilumab<br>* A total of 4 doses were administered.<br>* Other names: Dupixent;Other: Background treatment<br>* Participants were required to apply stable doses of an additive-free, basic bland emollient on the affected areas of the skin twice daily throughout the study.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant who received investigational medicinal product (IMP) without regard to possibility of causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a study drug, whether or not considered related to the study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study visit [Day 85]). Any TEAE included participants with both serious and non-serious AEs. | Baseline up to end of study (up to Day 85) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of Dupilumab: Peak Plasma Concentration (Cmax) | Maximum Plasma Concentration of functional Dupilumab observed following the fourth (last) dose. | Day 22 (pre-dose), 25, 29, 36, 43, 50, 57, 64, 71 and Day 85 | 
| Pharmacokinetics of Dupilumab: Last Positive (Quantifiable) Concentration (Clast) | Last Positive (Quantifiable) Concentration of Dupilumab. | Day 22 (pre-dose), 25, 29, 36, 43, 50, 57, 64, 71 and Day 85 | 
| Pharmacokinetics of Dupilumab: Time of the Last Positive (Quantifiable) Concentration (Tlast) | Mean time of last measurable concentration of Dupilumab in actual days. | Day 22 (pre-dose), 25, 29, 36, 43, 50, 57, 64, 71 and Day 85 |