A Study to Assess the Efficacy and Safety of Dupilumab in Participants With Severe Atopic Dermatitis (AD) That Are Not Controlled With Oral Cyclosporine A (CSA) or for Those Who Cannot Take Oral CSA Because it is Not Medically Advisable

NCT02755649 | Completed Phase 3 Results DMC

• 1 other identifier: R668-AD-1424
• Study Type: interventional
• Target: 325
• Locations: 10 countries
• Sites: 73

Brief Summary

The main objective of the trial is to evaluate the efficacy of 2 dose regimens of dupilumab compared to placebo, administered with concomitant topical corticosteroids (TCS), in adult patients with severe AD who are not adequately controlled with, or are intolerant to, oral Cyclosporine A (CSA), or when this treatment is currently not medically advisable. The secondary objective is to assess the safety and tolerability of 2 dose regimens of dupilumab compared to placebo, administered with concomitant TCS, in adult patients with severe AD who are not adequately controlled with, or are intolerant to, oral CSA, or when this treatment is currently not medically advisable.

Conditions

Atopic Dermatitis

Outcome Measures

Primary Outcomes (1)

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

  The EASI score is used to measure the severity and extent of atopic dermatitis (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-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. The analysis population for efficacy analyses is the Full Analysis Set (FAS) which included all randomized participants. Efficacy analyses were based on the treatment allocated (as randomized).

  Baseline, Week 16

Secondary Outcomes (18)

• Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16

  Baseline, Week 16

• Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) at Week 16

  Baseline, Week 16

• Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 16

  Baseline, Week 16

• Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus NRS From Baseline to Week 16

  Baseline to Week 16

• Change From Baseline in Percent Body Surface Area (BSA) Involvement With Atopic Dermatitis (AD) at Week 16

  Baseline, Week 16

Study Arms (3)

Placebo QW + TCS

EXPERIMENTAL

Participants received one subcutaneous (SC) injection of dupilumab matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).

Drug: Matching Placebo

Dupilumab 300 mg Q2W + TCS

EXPERIMENTAL

Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).

Drug: Dupilumab

Dupilumab 300 mg QW + TCS

EXPERIMENTAL

Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety (\[Week 28, end of study (EOS) period\]).

Drug: Dupilumab

Interventions

Dupilumab DRUG

Also known as: DUPIXENT®, REGN668, SAR231893

Dupilumab 300 mg Q2W + TCS; Dupilumab 300 mg QW + TCS

Matching Placebo DRUG

Placebo QW + TCS

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
• Severe, Chronic AD, (according to American Academy of Dermatology Consensus Criteria \[Eichenfield 2014\]) for whom treatment with potent TCS is indicated
• EASI score ≥20 at the screening and baseline visits
• IGA score ≥3 (on the 0 to 4 IGA scale) 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 TCS
• Have applied a stable dose of topical emollient (moisturizer) twice daily for at least the 7 consecutive days immediately before the baseline visit
• Documented history by a physician of either:
• No prior CSA exposure and not currently a candidate for CSA treatment due to:
• medical contraindications (eg, uncontrolled hypertension on medication), or
• use of prohibited concomitant medications (eg, statins, digoxin, macrolide, antibiotics, barbiturates, anti-seizure, nonsteroidal anti-inflammatory drugs, diuretics, angiotensin-converting-enzyme inhibitors, St John's Wort, etc), or
• increased susceptibility to CSA-induced renal damage (elevated creatinine) and liver damage (elevated function tests), or
• increased risk of serious infections, or
• hypersensitivity to CSA active substance or excipients OR
• Previously exposed to CSA, and CSA treatment should not be continued or restarted due to:

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 is longer, before the screening visit
• Hypersensitivity and/or intolerance to corticosteroids or to any other ingredients contained in the TCS product used in the study
• Systemic CSA, systemic corticosteroids, or phototherapy within 4 weeks prior to screening, and azathioprine (AZA), methotrexate (MTX), mycophenolate mofetil (MMF), or Janus kinase (JAK) inhibitors within 8 weeks prior to screening
• Treatment with TCI within 1 week before the screening visit
• Treatment with biologics as follows:
• Any cell-depleting agents including but not limited to rituximab: within 6 months before the screening visit, or until lymphocyte count returns to normal, whichever is longer
• Other biologics: within 5 half-lives (if known) or 16 weeks prior to the screening visit, whichever is longer
• Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the screening visit
• Treatment with a live (attenuated) vaccine within 12 weeks before the screening
• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the screening or superficial skin infections within 1 week before the screening visit. NOTE: patients may be rescreened no sooner than 2 weeks after infection resolves
• Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, tuberculosis \[TB\], histoplasmosis, Listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution; or unusually frequent, recurrent, or prolonged infections, per investigator judgment
• Presence of any 1 of the following TB criteria:
• A positive tuberculin skin test at the screening visit
• A positive blood QuantiFERON®-TB or T-Spot test at the screening visit

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (73)

Site 1

Vienna, Austria

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Vienna, Austria

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Brussels, Belgium

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Leuven, Belgium

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Loverval, Belgium

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Site 1

Berlin, Germany

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Berlin, Germany

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Berlin, Germany

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Site 4

Berlin, Germany

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Site 5

Berlin, Germany

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Site 6

Berlin, Germany

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Berlin, Germany

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Bochum, Germany

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Dresden, Germany

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Dresden, Germany

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Dresden, Germany

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Erlangen, Germany

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Frankfurt am Main, Germany

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Hamburg, Germany

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Hamburg, Germany

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Heidelberg, Germany

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Kiel, Germany

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Langenau, Germany

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Leipzig, Germany

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Lübeck, Germany

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Magdeburg, Germany

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Mahlow, Germany

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Mainz, Germany

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München, Germany

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München, Germany

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Münster, Germany

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Osnabrück, Germany

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Selters, Germany

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Stuttgart, Germany

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Tübingen, Germany

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Dublin, Ireland

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Amsterdam, Netherlands

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Utrecht, Netherlands

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Bialystok, Poland

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Bydgoszcz, Poland

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Bydgoszcz, Poland

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Gdansk, Poland

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Katowice, Poland

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Katowice, Poland

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Katowice, Poland

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Kielce, Poland

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Krakow, Poland

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Krakow, Poland

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Lodz, Poland

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Lodz, Poland

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Lodz, Poland

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Lublin, Poland

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Szczecin, Poland

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Warsaw, Poland

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Warsaw, Poland

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Warsaw, Poland

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Wroclaw, Poland

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Wroclaw, Poland

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Zgierz, Poland

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Chelyabinsk, Russia

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Kazan', Russia

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Moscow, Russia

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Ryazan, Russia

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Saint Petersburg, Russia

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Košice, Slovakia

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Svidník, Slovakia

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Site 1

Barcelona, Spain

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Barcelona, Spain

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London, United Kingdom

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London, United Kingdom

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Oxford, United Kingdom

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Portsmouth, United Kingdom

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Sheffield, United Kingdom

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Related Publications (8)

• 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

• Mickevicius T, Pink AE, Bhogal M, O'Brart D, Robbie SJ. Dupilumab-Induced, Tralokinumab-Induced, and Belantamab Mafodotin-Induced Adverse Ocular Events-Incidence, Etiology, and Management. Cornea. 2023 Apr 1;42(4):507-519. doi: 10.1097/ICO.0000000000003162. Epub 2022 Dec 15.

  PMID: 36525340 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

• 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

• 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

• de Bruin-Weller M, Graham NMH, Pirozzi G, Shumel B. Could conjunctivitis in patients with atopic dermatitis treated with dupilumab be caused by colonization with Demodex and increased interleukin-17 levels?: reply from the authors. Br J Dermatol. 2018 May;178(5):1220-1221. doi: 10.1111/bjd.16348. Epub 2018 Mar 2. No abstract available.

  PMID: 29336016 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 Administrator
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

844-734-6643

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2016
• First Posted: April 29, 2016
• Study Start: January 31, 2016
• Primary Completion: January 4, 2017
• Study Completion: March 31, 2017
• Last Updated: August 20, 2020
• Results First Posted: August 20, 2020

Record last verified: 2020-08

Locations

GB (5); AU (2); IE (1); DE (30); NL (2); ES (2); PL (21); RU (5); SL (2); BE (3)