Clinical trial NCT02277743: Study of Dupilumab Monotherapy Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis
Official title: A Phase 3 Confirmatory Study Investigating the Efficacy and Safety of Dupilumab Monotherapy Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dermatitis, Atopic
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2014-10-29
Enrollment: 671
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

1. Male or female, 18 years or older
2. 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;
3. Eczema Area and Severity Index (EASI) Score ≥16 at the screening and baseline visits;
4. 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;
5. ≥10% body surface area (BSA) of AD involvement at the screening and baseline visits;
6. 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).

Exclusion Criteria:

1. Participation in a prior Dupilumab clinical study;
2. Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever was longer, before the baseline visit;
3. 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
4. Treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within 1 week before the baseline visit;
5. 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
6. Regular use (more than 2 visits per week) of a tanning booth/ parlor within 4 weeks of the screening visit;
7. Planned or anticipated use of any prohibited medications and procedures during study treatment;
8. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit;
9. 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;
10. 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;
11. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening;
12. Positive with hepatitis B surface antigen (HBsAg) or hepatitis C antibody at the screening visit;
13. Participant was a member of the investigational team or his/her immediate family;
14. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study;
15. Women unwilling to use adequate birth control, if of reproductive potential and sexually active.

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

Primary outcomes:
measure: Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Percentage of Participants With Improvement (Reduction ≥3 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Percent Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16
timeFrame: Baseline to Week 16
measure: Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4
timeFrame: Baseline to Week 4
measure: Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2
timeFrame: Baseline to Week 2
measure: Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16
timeFrame: Baseline to Week 16
measure: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16
timeFrame: Baseline to Week 16
measure: Percentage of Participants With Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Eczema Area and Severity Index-90 (EASI-90) (≥90% Improvement From Baseline) at Week 16
timeFrame: Week 16
measure: Change From Baseline in Percent Body Surface Area (BSA) to Week 16
timeFrame: Baseline to Week 16
measure: Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16
timeFrame: Baseline to Week 16
measure: Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16
timeFrame: Baseline to Week 16
measure: Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16
timeFrame: Baseline to Week 16
measure: Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16
timeFrame: Baseline to Week 16
measure: Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 16
timeFrame: Baseline to Week 16
measure: Percent Change From Baseline in Peak Daily Pruritus NRS Score to Week 2
timeFrame: Baseline to Week 2
measure: Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) Requiring Systemic Treatment
timeFrame: Baseline up to Week 16
measure: Percentage of Participants With Treatment Emergent Serious Adverse Events (TESAEs) From Baseline Through Week 16
timeFrame: Baseline up to Week 16
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Treatment Discontinuation From Baseline Through Week 16
timeFrame: Baseline up to Week 16
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Fort Smith
country: United States
state: Arkansas
city: Rogers
country: United States
state: Arkansas
city: Clovis
country: United States
state: California
city: Lomita
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Oceanside
country: United States
state: California
city: Palmdale
country: United States
state: California
city: Rolling Hills Estates
country: United States
state: California
city: San Diego
country: United States
state: California
city: Santa Monica
country: United States
state: California
city: Stockton
country: United States
state: California
city: Boca Raton
country: United States
state: Florida
city: Clearwater
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Miami Lakes
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Pensacola
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Newnan
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Normal
country: United States
state: Illinois
city: Evansville
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Louisville
country: United States
state: Kentucky
city: Boston
country: United States
state: Massachusetts
city: Troy
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Newington
country: United States
state: New Hampshire
city: East Windsor
country: United States
state: New Jersey
city: Buffalo
country: United States
state: New York
city: Corning
country: United States
state: New York
city: New Hyde Park
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: High Point
country: United States
state: North Carolina
city: Bethlehem
country: United States
state: Pennsylvania
city: Upland
country: United States
state: Pennsylvania
city: Chattanooga
country: United States
state: Tennessee
city: Knoxville
country: United States
state: Tennessee
city: San Antonio
country: United States
state: Texas
city: Waco
country: United States
state: Texas
city: Ogden
country: United States
state: Utah
city: Newport News
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Dupnitsa
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Winnepeg
country: Canada
state: Manitoba
city: Bathurst
country: Canada
state: New Brunswick
city: Hamilton
country: Canada
state: Ontario
city: Mississauga
country: Canada
state: Ontario
city: Newmarket
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Richmond Hill
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Copenhagen
country: Denmark
city: Hellerup
country: Denmark
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Helsinki
country: Finland
city: Tampere
country: Finland
city: Turku
country: Finland
city: Berlin
country: Germany
city: Bielefed
country: Germany
city: Blaubeuren
country: Germany
city: Erlangen
country: Germany
city: Halle
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Muenster
country: Germany
city: Munchen
country: Germany
city: Osnabruck
country: Germany
city: Schwerin
country: Germany
city: Stuttgart
country: Germany
city: Kurume
country: Japan
state: Fukuoka
city: Fukuyama
country: Japan
state: Hiroshima
city: Inashiki
country: Japan
state: Ibaraki
city: Yokohama
country: Japan
state: Kanagawa
city: Habikino
country: Japan
state: Osaka
city: Neyagawa
country: Japan
state: Osaka
city: Sakai
country: Japan
state: Osaka
city: Takatsuki
country: Japan
state: Osaka
city: Hamamatsu
country: Japan
state: Shizuoka
city: Bunkyo-ku
country: Japan
state: Tokyo
city: Chuo-ku
country: Japan
state: Tokyo
city: Nerima-ku
country: Japan
state: Tokyo
city: Shinagawa
country: Japan
state: Tokyo
city: Shinjuku
country: Japan
state: Tokyo
city: Kofu
country: Japan
state: Yamanashi
city: Gifu
country: Japan
city: Hiroshima
country: Japan
city: Kyoto
country: Japan
city: Osaka
country: Japan
city: Singapore
country: Singapore
city: Alcaniz
country: Spain
city: Alicante
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: 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.
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citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.