Study of Dupilumab Monotherapy Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis

NCT02277743 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: R668-AD-1334
• Study Type: interventional
• Target: 671
• Locations: 9 countries
• Sites: 99

Brief Summary

This is a randomized, double-blind, placebo-controlled, parallel group study to confirm the efficacy and safety of Dupilumab monotherapy in adults with moderate-to-severe atopic dermatitis (AD).

Conditions

Dermatitis, Atopic

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points at Week 16

  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" and a reduction from baseline of ≥2 points at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 16 were considered as non-responders.

  Week 16

Secondary Outcomes (20)

• Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16

  Week 16

• Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16

  Baseline to Week 16

• Percentage of Participants With Improvement (Reduction ≥3 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16

  Baseline to Week 16

• Percent Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16

  Baseline to Week 16

• Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4

  Baseline to Week 4

Study Arms (3)

Placebo

EXPERIMENTAL

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 (for Dupilumab)

Dupilumab 300 mg once weekly (qw)

EXPERIMENTAL

Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15.

Drug: Dupilumab

Dupilumab 300 mg every 2 weeks (q2w)

EXPERIMENTAL

Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15.

Drug: Dupilumab; Drug: Placebo (for Dupilumab)

Interventions

Dupilumab DRUG

Subcutaneous injection alternated among the different quadrants of the abdomen, upper thighs and upper arms

Also known as: REGN668, SAR231893, DUPIXENT®

Dupilumab 300 mg every 2 weeks (q2w); Dupilumab 300 mg once weekly (qw)

Placebo (for Dupilumab) DRUG

Subcutaneous injection alternated among the different quadrants of the abdomen, upper thighs and upper arms

Dupilumab 300 mg every 2 weeks (q2w); Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, 18 years or older
• Chronic AD (according to American Academy of Dermatology Consensus Criteria Eichenfield 2014) that has been present for at least 3 years before the screening visit;
• Eczema Area and Severity Index (EASI) Score ≥16 at the screening and baseline visits;
• Investigator's Global Assessment (IGA) Score ≥3 (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) at the screening and baseline visits;
• ≥10% body surface area (BSA) of AD involvement at the screening and baseline visits;
• Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable (e.g, because of important side effects or safety risks).

You may not qualify if:

• Participation in a prior Dupilumab clinical study;
• Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever was longer, before the baseline visit;
• Having used any of the following treatments within 4 weeks before the baseline visit, or any condition that, in the opinion of the investigator, was likely to require such treatment(s) during the first 4 weeks of study treatment:
• Immunosuppressive/ immunomodulating drugs (e.g, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.);
• Phototherapy for AD
• Treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within 1 week before the baseline visit;
• Treatment with biologics as follows:
• Any cell-depleting agents including but not limited to rituximab: within 6 months before the baseline visit, or until lymphocyte count returns to normal, whichever was longer
• Other biologics: within 5 half-lives (if known) or 16 weeks prior to baseline visit, whichever was longer
• Regular use (more than 2 visits per week) of a tanning booth/ parlor within 4 weeks of the screening visit;
• Planned or anticipated use of any prohibited medications and procedures during study treatment;
• Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit;
• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit. NOTE: Participants might be rescreened after infection resolves;
• Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g, tuberculosis \[TB\], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per investigator judgment;
• History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening;

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (101)

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Birmingham, Alabama, United States

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Fort Smith, Arkansas, United States

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Rogers, Arkansas, United States

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Clovis, California, United States

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Lomita, California, United States

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Los Angeles, California, United States

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Oceanside, California, United States

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Palmdale, California, United States

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Rolling Hills Estates, California, United States

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San Diego, California, United States

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Santa Monica, California, United States

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Stockton, California, United States

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Boca Raton, Florida, United States

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Clearwater, Florida, United States

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Fort Lauderdale, Florida, United States

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Miami, Florida, United States

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Miami Lakes, Florida, United States

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Pensacola, Florida, United States

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Tampa, Florida, United States

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Newnan, Georgia, United States

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Chicago, Illinois, United States

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Normal, Illinois, United States

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Evansville, Indiana, United States

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Indianapolis, Indiana, United States

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Louisville, Kentucky, United States

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Boston, Massachusetts, United States

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Troy, Michigan, United States

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St Louis, Missouri, United States

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Newington, New Hampshire, United States

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East Windsor, New Jersey, United States

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Buffalo, New York, United States

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Corning, New York, United States

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New Hyde Park, New York, United States

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Rochester, New York, United States

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High Point, North Carolina, United States

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Bethlehem, Pennsylvania, United States

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Upland, Pennsylvania, United States

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Chattanooga, Tennessee, United States

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Knoxville, Tennessee, United States

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San Antonio, Texas, United States

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Waco, Texas, United States

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Ogden, Utah, United States

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Newport News, Virginia, United States

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Norfolk, Virginia, United States

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Spokane, Washington, United States

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Dupnitsa, Bulgaria

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Plovdiv, Bulgaria

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Sofia, Bulgaria

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Winnepeg, Manitoba, Canada

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Bathurst, New Brunswick, Canada

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Hamilton, Ontario, Canada

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Mississauga, Ontario, Canada

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Newmarket, Ontario, Canada

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Ottawa, Ontario, Canada

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Richmond Hill, Ontario, Canada

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Toronto, Ontario, Canada

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Copenhagen, Denmark

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Hellerup, Denmark

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Tallinn, Estonia

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Tartu, Estonia

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Helsinki, Finland

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Tampere, Finland

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Turku, Finland

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Berlin, Germany

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Bielefed, Germany

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Blaubeuren Abbey, Germany

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Erlangen, Germany

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Halle, Germany

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Hamburg, Germany

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Hanover, Germany

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München, Germany

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Münster, Germany

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Osnabrück, Germany

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Schwerin, Germany

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Stuttgart, Germany

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Kurume, Fukuoka, Japan

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Fukuyama, Hiroshima, Japan

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Inashiki, Ibaraki, Japan

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Yokohama, Kanagawa, Japan

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Habikino, Osaka, Japan

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Neyagawa, Osaka, Japan

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Sakai, Osaka, Japan

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Takatsuki, Osaka, Japan

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Hamamatsu, Shizuoka, Japan

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Bunkyo-ku, Tokyo, Japan

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Chuo-ku, Tokyo, Japan

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Nerima-ku, Tokyo, Japan

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Shinagawa, Tokyo, Japan

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Shinjuku, Tokyo, Japan

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Kofu, Yamanashi, Japan

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Gifu, Japan

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Hiroshima, Japan

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Kyoto, Japan

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Osaka, Japan

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Singapore, Singapore

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Alcañiz, Spain

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Alicante, Spain

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Barcelona, Spain

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Madrid, Spain

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Seville, Spain

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Valencia, Spain

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Related Publications (18)

• Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, Silverberg JI, Deleuran M, Kataoka Y, Lacour JP, Kingo K, Worm M, Poulin Y, Wollenberg A, Soo Y, Graham NM, Pirozzi G, Akinlade B, Staudinger H, Mastey V, Eckert L, Gadkari A, Stahl N, Yancopoulos GD, Ardeleanu M; SOLO 1 and SOLO 2 Investigators. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med. 2016 Dec 15;375(24):2335-2348. doi: 10.1056/NEJMoa1610020. Epub 2016 Sep 30.

  PMID: 27690741 RESULT

• Langley RG, Gherardi G, Coleman A, Ardeleanu M, Rodriguez-Marco A, Levy S, Bansal A, Chen Z, Rossi AB, Shumel B, Khokhar FA. The Safety Data of Dupilumab for the Treatment of Moderate-to-Severe Atopic Dermatitis in Infants, Children, Adolescents, and Adults. Am J Clin Dermatol. 2025 Nov;26(6):981-1002. doi: 10.1007/s40257-025-00952-w. Epub 2025 Sep 24.

  PMID: 40993471 DERIVED

• Kamal MA, Kosloski MP, Lai CH, Partridge MA, Rajadhyaksha M, Kanamaluru V, Bansal A, Shabbir A, Shumel B, Ardeleanu M, Richards SM, Yan H, Xu CR, Rodriguez-Marco A, Xiao J, Khokhar FA, Gherardi G, Babilonia E, Maloney J, Mortensen E, Akinlade B, Braunstein N, Stahl N, Torri A, Davis JD, DiCioccio AT. Immunogenicity of dupilumab in adult and pediatric patients with atopic dermatitis. Front Immunol. 2024 Nov 11;15:1466372. doi: 10.3389/fimmu.2024.1466372. eCollection 2024.

  PMID: 39588375 DERIVED

• Silverberg JI, Lynde CW, Abuabara K, Patruno C, de Benedetto A, Zhang H, Thomas RB, Bego-Le-Bagousse G, Khokhar FA, Vakil J, Marco AR, Levit NA. Efficacy and Safety of Dupilumab Maintained in Adults >/= 60 Years of Age with Moderate-to-Severe Atopic Dermatitis: Analysis of Pooled Data from Four Randomized Clinical Trials. Am J Clin Dermatol. 2023 May;24(3):469-483. doi: 10.1007/s40257-022-00754-4. Epub 2023 Feb 20.

  PMID: 36808602 DERIVED

• Paller AS, Silverberg JI, Cork MJ, Guttman-Yassky E, Lockshin B, Irvine AD, Kim MB, Kabashima K, Chen Z, Lu Y, Bansal A, Rossi AB, Shabbir A. Efficacy and Safety of Dupilumab in Patients With Erythrodermic Atopic Dermatitis: A Post Hoc Analysis of 6 Randomized Clinical Trials. JAMA Dermatol. 2023 Mar 1;159(3):255-266. doi: 10.1001/jamadermatol.2022.6192.

  PMID: 36723913 DERIVED

• Silverberg JI, Boguniewicz M, Hanifin J, Papp KA, Zhang H, Rossi AB, Levit NA. Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis is Efficacious Regardless of Age of Disease Onset: a Post Hoc Analysis of Two Phase 3 Clinical Trials. Dermatol Ther (Heidelb). 2022 Dec;12(12):2731-2746. doi: 10.1007/s13555-022-00822-x. Epub 2022 Oct 21.

  PMID: 36269503 DERIVED

• Wechsler ME, Klion AD, Paggiaro P, Nair P, Staumont-Salle D, Radwan A, Johnson RR, Kapoor U, Khokhar FA, Daizadeh N, Chen Z, Laws E, Ortiz B, Jacob-Nara JA, Mannent LP, Rowe PJ, Deniz Y. Effect of Dupilumab on Blood Eosinophil Counts in Patients With Asthma, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis, or Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2022 Oct;10(10):2695-2709. doi: 10.1016/j.jaip.2022.05.019. Epub 2022 May 28.

  PMID: 35636689 DERIVED

• Armstrong A, Blauvelt A, Simpson EL, Smith CH, Herranz P, Kataoka Y, Seo SJ, Ferrucci SM, Chao J, Chen Z, Rossi AB, Shumel B, Tomondy P. Continued Treatment with Dupilumab is Associated with Improved Efficacy in Adults with Moderate-to-Severe Atopic Dermatitis Not Achieving Optimal Responses with Short-Term Treatment. Dermatol Ther (Heidelb). 2022 Jan;12(1):195-202. doi: 10.1007/s13555-021-00643-4. Epub 2021 Dec 13.

  PMID: 34897582 DERIVED

• Paller AS, Tan JKL, Bagel J, Rossi AB, Shumel B, Zhang H, Abramova A. IGAxBSA composite for assessing disease severity and response in patients with atopic dermatitis. Br J Dermatol. 2022 Mar;186(3):496-507. doi: 10.1111/bjd.20872. Epub 2022 Feb 25.

  PMID: 34726270 DERIVED

• Griffiths C, de Bruin-Weller M, Deleuran M, Fargnoli MC, Staumont-Salle D, Hong CH, Sanchez-Carazo J, Foley P, Seo SJ, Msihid J, Chen Z, Cyr SL, Rossi AB. Dupilumab in Adults with Moderate-to-Severe Atopic Dermatitis and Prior Use of Systemic Non-Steroidal Immunosuppressants: Analysis of Four Phase 3 Trials. Dermatol Ther (Heidelb). 2021 Aug;11(4):1357-1372. doi: 10.1007/s13555-021-00558-0. Epub 2021 Jun 18.

  PMID: 34142350 DERIVED

• Hamilton JD, Harel S, Swanson BN, Brian W, Chen Z, Rice MS, Amin N, Ardeleanu M, Radin A, Shumel B, Ruddy M, Patel N, Pirozzi G, Mannent L, Graham NMH. Dupilumab suppresses type 2 inflammatory biomarkers across multiple atopic, allergic diseases. Clin Exp Allergy. 2021 Jul;51(7):915-931. doi: 10.1111/cea.13954. Epub 2021 Jun 26.

  PMID: 34037993 DERIVED

• Boguniewicz M, Beck LA, Sher L, Guttman-Yassky E, Thaci D, Blauvelt A, Worm M, Corren J, Soong W, Lio P, Rossi AB, Lu Y, Chao J, Eckert L, Gadkari A, Hultsch T, Ruddy M, Mannent LP, Graham NMH, Pirozzi G, Chen Z, Ardeleanu M. Dupilumab Improves Asthma and Sinonasal Outcomes in Adults with Moderate to Severe Atopic Dermatitis. J Allergy Clin Immunol Pract. 2021 Mar;9(3):1212-1223.e6. doi: 10.1016/j.jaip.2020.12.059. Epub 2021 Jan 13.

  PMID: 33453450 DERIVED

• Silverberg JI, Simpson EL, Guttman-Yassky E, Cork MJ, de Bruin-Weller M, Yosipovitch G, Eckert L, Chen Z, Ardeleanu M, Shumel B, Hultsch T, Rossi AB, Hamilton JD, Orengo JM, Ruddy M, Graham NMH, Pirozzi G, Gadkari A. Dupilumab Significantly Modulates Pain and Discomfort in Patients With Atopic Dermatitis: A Post Hoc Analysis of 5 Randomized Clinical Trials. Dermatitis. 2021 Oct 1;32(1S):S81-S91. doi: 10.1097/DER.0000000000000698.

  PMID: 33165005 DERIVED

• Alexis AF, Rendon M, Silverberg JI, Pariser DM, Lockshin B, Griffiths CE, Weisman J, Wollenberg A, Chen Z, Davis JD, Li M, Eckert L, Gadkari A, Shumel B, Rossi AB, Graham NM, Ardeleanu M. Efficacy of Dupilumab in Different Racial Subgroups of Adults With Moderate-to-Severe Atopic Dermatitis in Three Randomized, Placebo-Controlled Phase 3 Trials. J Drugs Dermatol. 2019 Aug 1;18(8):804-813.

  PMID: 31424712 DERIVED

• Wollenberg A, Beck LA, Blauvelt A, Simpson EL, Chen Z, Chen Q, Shumel B, Khokhar FA, Hultsch T, Rizova E, Rossi AB, Graham NMH, Pirozzi G, Lu Y, Ardeleanu M. Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS). Br J Dermatol. 2020 May;182(5):1120-1135. doi: 10.1111/bjd.18434. Epub 2019 Dec 1.

  PMID: 31407311 DERIVED

• Eichenfield LF, Bieber T, Beck LA, Simpson EL, Thaci D, de Bruin-Weller M, Deleuran M, Silverberg JI, Ferrandiz C, Folster-Holst R, Chen Z, Graham NMH, Pirozzi G, Akinlade B, Yancopoulos GD, Ardeleanu M. Infections in Dupilumab Clinical Trials in Atopic Dermatitis: A Comprehensive Pooled Analysis. Am J Clin Dermatol. 2019 Jun;20(3):443-456. doi: 10.1007/s40257-019-00445-7.

  PMID: 31066001 DERIVED

• Silverberg JI, Simpson EL, Ardeleanu M, Thaci D, Barbarot S, Bagel J, Chen Z, Eckert L, Chao J, Korotzer A, Rizova E, Rossi AB, Lu Y, Graham NMH, Hultsch T, Pirozzi G, Akinlade B. Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator's Global Assessment: a pooled analysis of data from two phase III trials. Br J Dermatol. 2019 Jul;181(1):80-87. doi: 10.1111/bjd.17791. Epub 2019 Apr 11.

  PMID: 30791102 DERIVED

• Simpson EL. Dupilumab Improves General Health-Related Quality-of-Life in Patients with Moderate-to-Severe Atopic Dermatitis: Pooled Results from Two Randomized, Controlled Phase 3 Clinical Trials. Dermatol Ther (Heidelb). 2017 Jun;7(2):243-248. doi: 10.1007/s13555-017-0181-6. Epub 2017 May 13.

  PMID: 28503712 DERIVED

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Clinical Trial Management
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2014
• First Posted: October 29, 2014
• Study Start: October 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: February 1, 2016
• Last Updated: November 21, 2017
• Results First Posted: November 21, 2017

Record last verified: 2017-11

Locations

ES (6); DK (2); SG (1); DE (12); JP (19); BU (3); CA (8); US (45); FI (3)