Study to Assess the Safety of Dupilumab (REGN668/SAR231893) Administered Concomitantly With Topical Corticosteroids (TCS) in Patients With Moderate-to-severe Atopic Dermatitis (AD)

A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Assess the Safety of REGN668 Administered Concomitantly With Topical Corticosteroids to Patients With Moderate-to-Severe Atopic Dermatitis

The purpose of this study was to assess the safety of Dupilumab administered concomitantly with topical corticosteroids (TCS) in patients with moderate-to-severe atopic dermatitis (AD).

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Placebo (for Dupilumab); Other: Topical Corticosteroid (TCS); Drug: Dupilumab

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
  • Dresden, Germany
  • Duelmen, Germany
  • Frankfurt, Germany
  • Gera, Germany
  • Langenau, Germany
  • Munster, Germany
• Hungary
  • Szeged-Hungary, 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:

1. Male and female patients aged 18 years or older
2. Chronic AD that had been present for at least 2 years

Exclusion Criteria:

1. Prior treatment with Dupilumab
2. Hypersensitivity to corticosteroids or to any other ingredients contained by the TCS product used in the study
3. AD lesions located on face, flexural, and genital areas
4. Certain treatments and medical procedures, undertaken within a particular time frame prior to the baseline visit, preclude eligibility for participation in the study
5. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit
6. Treatment with an investigational drug within 8 weeks
7. Known history of human immunodeficiency virus (HIV) infection
8. Presence of certain laboratory abnormalities at the screening visit
9. History of certain opportunistic infections or certain clinical parasite infections
10. History of malignancy within 5 years before the baseline visit, with certain exceptions
11. Pregnant or breast-feeding women
12. Travel within 12 months of study start to areas endemic for parasitic infections, such as developing countries in Africa and the tropical and subtropical regions of Asia
13. History of alcohol or drug abuse within 2 years of the screening visit
14. Any medical or psychiatric condition which, in the opinion of the investigator or the sponsor's medical monitor, would place the patient at risk, interfere with participation in the study, or interfere with the interpretation of study results

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
Experimental: Placebo QW; Placebo (for Dupilumab) once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent topical corticosteroid (TCS) for up to 28 days	Drug: Placebo (for Dupilumab); Placebo (for Dupilumab) once weekly (QW) for 4 weeks; Other: Topical Corticosteroid (TCS); TCS such as methylprednisolone aceponate 0.1%, mometasone furoate 0.1%, or betamethasone valerate 0.1%
Experimental: Dupilumab 300 mg QW; Dupilumab 300 mg once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days	Other: Topical Corticosteroid (TCS); TCS such as methylprednisolone aceponate 0.1%, mometasone furoate 0.1%, or betamethasone valerate 0.1%; Drug: Dupilumab; Dupilumab 300 mg once weekly (QW) for 4 weeks; Other Names: Dupixent; REGN668; SAR231893

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)	Any untoward medical occurrence in a subject who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (from start of administration of first dose of study drug to the end of study [up to Day 78]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.	Baseline up to the end of study (up to Day 78)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Score: Reduction of ≥50 at Day 29 - Censored Last Observation Carried Forward (LOCF)	The EASI score was used to measure the severity and extent of atopic dermatitis (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 range from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. The efficacy data were set to missing after prohibited medication was used or after the participant was discontinued from the study. Then, all missing values were imputed by simple LOCF.	Day 29
Percent Change in Pruritus Numerical Rating Scale (NRS) From Day 1 (Baseline) to Day 29 (Week 4)	Pruritus NRS was an assessment tool that was used to report the intensity of 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]).	Baseline up to Day 29
Percentage of Participants Achieving an Investigator's Global Assessment (IGA) Score of "0" or "1" at Day 29	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).	Day 29
Percent Change in Investigator's Global Assessment (IGA) Score From Day 1 (Baseline) to Day 29 (Week 4) - Censored LOCF	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). The efficacy data were set to missing after prohibited medication was used or after the participant was discontinued from the study. Then, all missing values were imputed by simple LOCF.	Baseline up to Day 29
Percent Change in Eczema Area and Severity Index (EASI) Score From Day 1 (Baseline) to Day 29 (Week 4) - Censored LOCF	EASI score was used to measure the severity and extent of atopic dermatitis (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. The efficacy data were set to missing after prohibited medication was used or after the participant was discontinued from the study. Then, all missing values were imputed by simple LOCF.	Baseline up to Day 29

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.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: July 9, 2012
• First Submitted That Met QC Criteria: July 11, 2012
• First Posted (Estimate): July 12, 2012

Study Record Updates

• Last Update Posted (Actual): October 13, 2017
• Last Update Submitted That Met QC Criteria: May 22, 2017
• Last Verified: May 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; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: R668-AD-1121