Clinical trial NCT02277769: Study of Dupilumab (REGN668/SAR231893) 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: 708
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. Chronic AD that has been present for at least 3 years before the screening visit;
2. ≥10% body surface area (BSA) of AD involvement at the screening and baseline visits;
3. 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 (eg, 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 is 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, is likely to require such treatment(s) during the first 4 weeks of study treatment:

   * Immunosuppressive/ immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.)
   * Phototherapy for AD
4. Regular use (more than 2 visits per week) of a tanning booth/ parlor within 4 weeks of the screening visit;
5. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit;
6. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening;
7. Positive with hepatitis B surface antigen (HBsAg) or hepatitis C antibody at the screening visit;
8. Active chronic or acute infection requiring systemic treatment within 2 weeks before the baseline visit;
9. Known or suspected history of immunosuppression;
10. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study;
11. 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 Weekly Average of Peak Daily 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) in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Percent Change From Baseline in Weekly Average of Peak 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 Weekly Average of 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: Anniston
country: United States
state: Alabama
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Bakersfield
country: United States
state: California
city: Costa Mesa
country: United States
state: California
city: Fremont
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Orange
country: United States
state: California
city: Roseville
country: United States
state: California
city: Temecula
country: United States
state: California
city: Trumbull
country: United States
state: Connecticut
city: Miami
country: United States
state: Florida
city: Oviedo
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Alpharetta
country: United States
state: Georgia
city: Atlanta
country: United States
state: Georgia
city: Columbus
country: United States
state: Georgia
city: Buffalo Grove
country: United States
state: Illinois
city: Plainfield
country: United States
state: Indiana
city: West Des Moines
country: United States
state: Iowa
city: Overland Park
country: United States
state: Kansas
city: Rockville
country: United States
state: Maryland
city: Washington Park
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Farmington Hills
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Plymouth
country: United States
state: Minnesota
city: Saint Joseph
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Billings
country: United States
state: Montana
city: Bozeman
country: United States
state: Montana
city: Las Vegas
country: United States
state: Nevada
city: Verona
country: United States
state: New Jersey
city: Forest Hills
country: United States
state: New York
city: New York
country: United States
state: New York
city: Smithtown
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Tulsa
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Jenkintown
country: United States
state: Pennsylvania
city: Greer
country: United States
state: South Carolina
city: Arlington
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Bellaire
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Surrey
country: Canada
state: British Columbia
city: St. John's
country: Canada
state: Newfoundland and Labrador
city: Ajax
country: Canada
state: Ontario
city: Mississauga
country: Canada
state: Ontario
city: Oakville
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Peterborough
country: Canada
state: Ontario
city: Richmond Hill
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Lille Cedex
country: France
city: Marseille
country: France
city: Nantes
country: France
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Darmstadt
country: Germany
city: Friedrichshafen
country: Germany
city: Hamburg
country: Germany
city: Kiel
country: Germany
city: Hong Kong
country: Hong Kong
city: Lucca
country: Italy
city: Pisa
country: Italy
city: Roma
country: Italy
city: Busan
country: Korea, Republic of
city: Gyeonggi-do
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Vilnius
country: Lithuania
city: Elblag
country: Poland
city: Gdansk
country: Poland
city: Katowice
country: Poland
city: Poznan
country: Poland
city: Torun
country: Poland
city: Warsaw
country: Poland
city: Stockholm
country: Sweden
city: London
country: United Kingdom
city: Plymouth
country: United Kingdom
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.