Study of Dupilumab in Adult Patients With Extrinsic Moderate-to-Severe Atopic Dermatitis

A Randomized, Double-Blind, Placebo-Controlled, Repeat-Dose Study of the Efficacy, Safety, Tolerability, and Pharmacodynamics of Subcutaneously-Administered REGN668 in Adult Patients With Extrinsic Moderate-to-Severe Atopic Dermatitis

The primary objective was to assess the clinical efficacy of repeated subcutaneous (SC) doses of Dupilumab in adult participants with moderate-to-severe atopic dermatitis (AD).

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Placebo; Drug: Dupilumab

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Nachod, Czechia
  • Svitavy, Czechia
  • Usti nad Labem, Czechia
• France
  • Nice, France
  • Pierre Bénite, France
  • Toulouse, France
• Germany
  • Berlin, Germany
  • Bonn, Germany
  • Frankfurt, Germany
  • Gera, Germany
  • Heidelberg, Germany
  • Kiel, Germany
  • Münster, Germany
• Hungary
  • Kaposvar, Hungary
  • Szeged, Hungary
  • Szekszard, Hungary
  • Szolnok, Hungary
• Poland
  • Gdansk, Poland
  • Lodz, Poland
  • Lublin, Poland
  • Warszawa, Poland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

The inclusion criteria included, but were not limited to the following:

1. Male or female, 18 years or older;
2. Chronic Atopic Dermatitis (AD) for at least 3 years;
3. 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:

1. Prior treatment with REGN668;
2. Presence of certain laboratory abnormalities at the screening visit;
3. Treatment with an investigational drug within 8 weeks ;
4. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit;
5. Certain treatments and medical procedures, undertaken within a particular time-frame prior to the baseline visit, preclude eligibility for participation in the study;
6. Known history of human immunodeficiency virus (HIV) infection;
7. History of malignancy within 5 years before the baseline visit, with certain exceptions;
8. Planned surgical procedure during the length of the patient's participation in this study;
9. History of clinical parasite infection;
10. 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;
11. Pregnant or breast-feeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo (for Dupilumab) once weekly for 12 weeks by subcutaneous (SC) injection.	Drug: Placebo; Subcutaneous injection altered between back of arms, abdomen and upper thighs.
Experimental: Dupilumab 300 mg; Dupilumab 300 mg once weekly for 12 weeks by SC injection.	Drug: Dupilumab; Subcutaneous injection altered between back of arms, abdomen and upper thighs.; Other Names: Dupixent; REGN668/SAR231893

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 12- Last Observation Carried Forward (LOCF)	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. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" at Week 12- LOCF	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). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.	Week 12
Percentage of Participants Who Achieved at Least a 50% Reduction From Baseline in the EASI Score (EASI-50) at Week 12- LOCF	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 12. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.	Week 12
Change From Baseline in EASI Score at Week 12- LOCF	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. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.	Baseline to Week 12
Percent Change From Baseline in IGA Score at Week 12- LOCF	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). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.	Baseline to Week 12
Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 12 - LOCF	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. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.	Baseline to Week 12
Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 12- LOCF	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). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.	Baseline to Week 12
Change From Baseline in Pruritus Numerical Rating Scale (NRS) to Week 12- LOCF	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]). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.	Baseline to Week 12
Change From Baseline in 5-D Pruritus Scale at Week 12	The 5-D Pruritus Scale is a 1-page, 5-question tool used in clinical trials to assess 5 dimensions of background itch: degree, duration, direction, disability, and distribution. Each question corresponds to 1 of the 5 dimensions of itch; participants were to rate their symptoms over the preceding 2-week period on a 1 to 5 scale, with 5 being the most affected. After the summation of individual score, the total score ranges from 5 (least affected) to 25 (most affected).	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi

Publications and helpful links

General Publications

• Beck LA, Thaci D, Hamilton JD, Graham NM, Bieber T, Rocklin R, Ming JE, Ren H, Kao R, Simpson E, Ardeleanu M, Weinstein SP, Pirozzi G, Guttman-Yassky E, Suarez-Farinas M, Hager MD, Stahl N, Yancopoulos GD, Radin AR. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014 Jul 10;371(2):130-9. doi: 10.1056/NEJMoa1314768.
• Tsianakas A, Luger TA, Radin A. Dupilumab treatment improves quality of life in adult patients with moderate-to-severe atopic dermatitis: results from a randomized, placebo-controlled clinical trial. Br J Dermatol. 2018 Feb;178(2):406-414. doi: 10.1111/bjd.15905. Epub 2018 Jan 11.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: March 5, 2012
• First Submitted That Met QC Criteria: March 7, 2012
• First Posted (Estimate): March 8, 2012

Study Record Updates

• Last Update Posted (Actual): August 10, 2018
• Last Update Submitted That Met QC Criteria: November 13, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: R668-AD-1117