Study to Determine the Safety and Effectiveness of Dupilumab for Treatment of Atopic Dermatitis (AD)

• ClinicalTrials.gov Identifier: NCT01979016
• Recruitment Status: Completed
• First Posted: November 8, 2013
• Results First Posted: March 18, 2020
• Last Update Posted: March 18, 2020
• Sponsor: Regeneron Pharmaceuticals
• Collaborator: Sanofi
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

Brief Summary:

The primary objective of the study was to assess the efficacy of Dupilumab, compared to placebo, in adult patients with moderate-to-severe atopic dermatitis (AD).

Condition or disease	Intervention/treatment	Phase
Atopic Dermatitis (AD)	Drug: Dupilumab; Drug: Placebo; Other: Background treatment	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Investigating the Efficacy, Safety, Serum Concentration and Biomarker Profile of Dupilumab Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis
• Actual Study Start Date: December 31, 2013
• Actual Primary Completion Date: December 31, 2014
• Actual Study Completion Date: January 31, 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Placebo qw; Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection once weekly (qw) from Week 1 to Week 15.	Drug: Placebo; Matching placebo; Other: Background treatment; Participants were required to apply stable doses of a topical emollient (moisturizer) twice daily for at least 7 days before the baseline visit and at least 7 days after the baseline visit (day -7 to day 8).; Other Name: Topical emollient
Experimental: Dupilumab 200 mg qw; Two subcutaneous injections of Dupilumab 200 milligram (mg) (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.	Drug: Dupilumab; Other Names: REGN668; SAR231893; Dupixent; Other: Background treatment; Participants were required to apply stable doses of a topical emollient (moisturizer) twice daily for at least 7 days before the baseline visit and at least 7 days after the baseline visit (day -7 to day 8).; Other Name: Topical emollient

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in the Eczema Area Severity Index Score (EASI) to Week 16 [ Time Frame: Baseline to Week 16 ]
   The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema (E), infiltration (I), excoriation (Ex) and lichenification (L) 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 medication use were set to missing and missing values imputed by last observation carried forward (LOCF).

Secondary Outcome Measures :

1. Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" at Week 16 [ Time Frame: 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). Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were considered as non-responders.
2. Percentage of Participants Who Achieved IGA Score Reduction From Baseline of ≥2 Points at Week 16 [ Time Frame: Baseline to 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. Participants with reduction in IGA score from baseline of ≥2 points at Week 16 were reported. Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were treated as non-responders.
3. Absolute Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16 [ Time Frame: Baseline to Week 16 ]
   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 missing values were imputed by LOCF.
4. Percent Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16 [ Time Frame: Baseline to Week 16 ]
   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 missing values were imputed by LOCF.
5. Absolute Change From Baseline in EASI Score to Week 16 [ Time Frame: Baseline to Week 16 ]
   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 medication use were set to missing and missing values were imputed by LOCF.
6. Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16 [ Time Frame: Baseline to Week 16 ]
   SCORAD was a clinical tool for assessing the severity of atopic dermatitis 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.) were assessed and scored. Total score ranged from 0 (absent disease) to 103 (severe disease). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.
7. Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16 [ Time Frame: Baseline to Week 16 ]
   SCORAD is a clinical tool for assessing the severity of atopic dermatitis 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 medication use were set to missing and missing values were imputed by LOCF.
8. Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score ( EASI-50, EASI-75, and EASI-90 Respectively) at Week 16 [ Time Frame: Baseline to Week 16 ]
   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 ranged from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50, EASI-75 and EASI-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% respectively, overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.
9. Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 [ Time Frame: Baseline to Week 16 ]
   SCORAD was a clinical tool for assessing the severity of atopic dermatitis 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.) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). SCORAD-50, SCORAD-75 and SCORAD-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% respectively, overall improvement in SCORAD score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing SCORAD score at Week 16 were counted as non-responders.
10. Absolute Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16 [ Time Frame: Baseline to Week 16 ]
    POEM was a 7-item questionnaire that assessed disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.
11. Percent Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16 [ Time Frame: Baseline to Week 16 ]
    POEM was a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.
12. Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16 [ Time Frame: Baseline to Week 16 ]
    Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).Values after first rescue medication use were set to missing and missing values were imputed by LOCF.
13. Changes From Baseline in GISS Cumulative Score to Week 16 [ Time Frame: Baseline to Week 16 ]
    Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Male or female, 18 years or older;
2. Chronic AD that had been present for at least 3 years before the screening visit;
3. Patients with documented recent history (within 6 months before the screening visit) of inadequate response to out-patient treatment with topical medications, or for whom topical treatments were otherwise inadvisable;
4. Willing and able to comply with all clinic visits and study-related procedures.

Exclusion Criteria:

1. Prior participation in a Dupilumab clinical trial;
2. Treatment with an investigational drug within 8 weeks or within 5 half-lives before the baseline visit;

3. The following treatments within 4 weeks before the baseline visit, or any condition that, in the opinion of the investigator, will likely require such treatment(s) during the first 4 weeks of study treatment:

   • Systemic corticosteroids;
   • Immunosuppressive/immunomodulating drugs;
   • Phototherapy for AD;
4. Treatment with topical corticosteroids, tacrolimus and/or pimecrolimus within 1 week before the baseline visit;
5. Treatment with certain biologics;
6. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks before the baseline visit;
7. Planned major surgical procedure during the participant's participation in this study;
8. Participant was a member of the investigational team or his/her immediate family;
9. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit
10. Pregnant or breast-feeding women or women planning to become pregnant or breastfeed during the study;

Note: The information listed above is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial therefore not all inclusion/exclusion criteria are listed.

Contacts and Locations

Locations

United States, Illinois

Chicago, Illinois, United States

United States, New York

New York, New York, United States

United States, Texas

Dallas, Texas, United States

Canada, Quebec

Montreal, Quebec, Canada

Sponsors and Collaborators

Regeneron Pharmaceuticals

Sanofi

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Callewaert C, Nakatsuji T, Knight R, Kosciolek T, Vrbanac A, Kotol P, Ardeleanu M, Hultsch T, Guttman-Yassky E, Bissonnette R, Silverberg JI, Krueger J, Menter A, Graham NMH, Pirozzi G, Hamilton JD, Gallo RL. IL-4Rα Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis. J Invest Dermatol. 2020 Jan;140(1):191-202.e7. doi: 10.1016/j.jid.2019.05.024. Epub 2019 Jun 25.

Guttman-Yassky E, Bissonnette R, Ungar B, Suárez-Fariñas M, Ardeleanu M, Esaki H, Suprun M, Estrada Y, Xu H, Peng X, Silverberg JI, Menter A, Krueger JG, Zhang R, Chaudhry U, Swanson B, Graham NMH, Pirozzi G, Yancopoulos GD, D Hamilton JD. Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. J Allergy Clin Immunol. 2019 Jan;143(1):155-172. doi: 10.1016/j.jaci.2018.08.022. Epub 2018 Sep 5.

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01979016
• Other Study ID Numbers: R668-AD-1307
• First Posted: November 8, 2013
• Results First Posted: March 18, 2020
• Last Update Posted: March 18, 2020
• Last Verified: March 2020

Additional relevant MeSH terms:

Dermatitis, Atopic; Dermatitis; Eczema; Skin Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Emollients; Dermatologic Agents