Evaluation of the Efficacy and Safety of Lebrikizumab (LY3650150) in Moderate to Severe Atopic Dermatitis (ADvocate1)
A Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Lebrikizumab in Patients With Moderate to Severe Atopic Dermatitis
4 other identifiers
interventional
424
9 countries
93
Brief Summary
This is a randomized, double-blind, placebo-controlled, parallel-group study which is 52 weeks in duration. The study is designed to confirm the safety and efficacy of lebrikizumab as monotherapy for treatment of moderate-to-severe atopic dermatitis utilizing a 16-week induction treatment period and a 36-week long-term maintenance treatment period.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Sep 2019
Typical duration for phase_3
93 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 24, 2019
CompletedFirst Submitted
Initial submission to the registry
October 29, 2019
CompletedFirst Posted
Study publicly available on registry
October 31, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 21, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
May 3, 2022
CompletedResults Posted
Study results publicly available
August 29, 2022
CompletedNovember 30, 2022
November 1, 2022
1.7 years
October 29, 2019
June 20, 2022
November 2, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16
The IGA measures the investigator's global assessment of the participant's overall severity of their Atopic Dermatitis (AD), based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Baseline to Week 16
Percentage of Participants Achieving Eczema Area And Severity Index (EASI-75) (≥75% Reduction in EASI Score) From Baseline to Week 16
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent, i.e., percentage of skin affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI-75 score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe). The EASI-75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the EASI score.
Baseline to Week 16
Secondary Outcomes (38)
Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 2
Baseline to Week 2
Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 4
Baseline to Week 4
Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 in Adults
Baseline to Week 16
Percentage of Participants Achieving EASI-90 (≥90% Reduction in EASI Score) From Baseline to Week 16
Baseline to Week 16
Percent Change in Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
Baseline, Week 16
- +33 more secondary outcomes
Study Arms (4)
Placebo
PLACEBO COMPARATORInduction Period (Baseline-Week 16): Two subcutaneous (SC) injections of Placebo as a loading dose at Baseline and Week 2 followed by a single injection every 2 weeks (Q2W) from Week 4 until Week 14. Maintenance Period (Week 16-Week 52): Two placebo SC injections as loading dose on Week 16 and Week 18. One placebo SC injection Q2W until Week 50.
Lebrikizumab 250 Q2W
EXPERIMENTALInduction Period (Baseline-Week 16): 500 milligram (mg) Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 visits followed by a single 250 mg Lebrikizumab injection Q2W from Week 4 until Week 14. Maintenance Period (Week 16-Week 52): One 250 mg Lebrikizumab SC injection Q2W until Week 50. For participants who received placebo in the Induction Period, the maintenance loading dose is: Two 250 mg Lebrikizumab SC injections on Week 16. Two 250 mg Lebrikizumab SC injections on Week 18. To maintain the blind, for participants who received Lebrikizumab in the Induction Period, the maintenance loading dose is: One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 16. One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 18.
Lebrikizumab 250 Q4W
EXPERIMENTALMaintenance Period (Week 16-Week 52): One 250 mg Lebrikizumab SC injection every 4 weeks (Q4W) on Weeks 20, 24, 28, 32, 36, 40, 44, and 48. One placebo SC injection Q4W on Weeks 22, 26, 30, 34, 38, 42, 46, and 50. For participants who received placebo in the Induction Period, the maintenance loading dose is: Two 250 mg Lebrikizumab SC injections on Week 16. Two placebo injections on Week 18. To maintain the blind, for participants who received Lebrikizumab in the Induction Period, the maintenance loading dose is: One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 16. Two placebo injections on Week 18
Escape Arm (Lebrikizumab Q2W)
EXPERIMENTALMaintenance Period (Week 16-Week 52): Blinded loading doses based on prior treatment assignment will be administered, followed by one 250 mg Lebrikizumab SC injection Q2W until Week 50 in an open-label fashion. For participants who received placebo in the Induction Period, the loading dose is: Two 250 mg Lebrikizumab SC injections on Week 16. Two 250 mg Lebrikizumab SC injections on Week 18. To maintain the loading dose blind, for participants who received Lebrikizumab in the Induction Period, the loading dose is: One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 16. One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 18. For participants who do not maintain an acceptable response during the Maintenance Period and entered the Escape Arm, the loading doses will be administrated at entry and 2 weeks after entry based on the treatment assignment prior to entering escape arm.
Interventions
Subcutaneous injection
Subcutaneous Injection
Eligibility Criteria
You may qualify if:
- Male or female adults and adolescents (≥12 years and ≥40 kg)
- Chronic atopic dermatitis (according to American Academy of Dermatology Consensus Criteria) that has been present for ≥1 year before the screening visit
- Eczema Area and Severity Index (EASI) score ≥16 at the baseline visit
- Investigator Global Assessment (IGA) score ≥3 (scale of 0 to 4) at the baseline visit
- ≥10% body surface area (BSA) of atopic dermatitis involvement at the baseline visit
- History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable
You may not qualify if:
- Prior treatment with dupilumab or tralokinumab
- Treatment with topical corticosteroids, calcineurin inhibitors or phosphodiesterase-4 inhibitors such as crisaborole within 1 week prior to the baseline visit
- Treatment with any of the following agents within 4 weeks prior to the baseline visit:
- Immunosuppressive/immunomodulating drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.)
- Phototherapy and photochemotherapy (PUVA) for AD
- Treatment with the following prior to the baseline visit:
- An investigational drug within 8 weeks or within 5 half-lives (if known) of baseline, whichever is longer
- Cell-depleting biologics, including to rituximab, within 6 months of baseline
- Other biologics within 5 half-lives (if known) or 16 weeks of baseline, whichever is longer
- Treatment with a live (attenuated) vaccine within 12 weeks of the baseline visit or planned during the study
- Uncontrolled chronic disease that might require bursts of oral corticosteroids, e.g., co-morbid severe uncontrolled asthma
- Evidence of active acute or chronic hepatitis
- History of human immunodeficiency virus (HIV) infection or positive HIV serology
- History of malignancy, including mycosis fungoides, within 5 years before the screening visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin
- Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eli Lilly and Companylead
- Dermira, Inc.collaborator
Study Sites (94)
Johnson Dermatology
Fort Smith, Arkansas, 72916, United States
Wallace Medical Group, Inc.
Beverly Hills, California, 90211, United States
California Dermatology & Clinical Research Institute
Encinitas, California, 92024, United States
Belle Aimee Skincare Clinic
Fountain Valley, California, 92708, United States
Dermatology Research Associates
Los Angeles, California, 90045, United States
ACRC Studies
San Diego, California, 92119, United States
Central Connecticut Dermatology
Cromwell, Connecticut, 06416, United States
St. Francis Medical Institute
Clearwater, Florida, 33765, United States
Community Research Foundation Inc
Miami, Florida, 33145, United States
ForCare Clinical Research
Tampa, Florida, 33613-1244, United States
IACT Health - VHC
Columbus, Georgia, 31903, United States
The Indiana Clinical Trials Center
Plainfield, Indiana, 46168, United States
Skin Sciences, PLLC
Louisville, Kentucky, 40217, United States
Beacon Clinical Research, LLC
Quincy, Massachusetts, 02169, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
St Joseph Dermatology and Vein Clinic
Saint Joseph, Michigan, 49085, United States
MediSearch Clinical Trials
Saint Joseph, Missouri, 64506, United States
JDR Dermatology Research
Las Vegas, Nevada, 89148, United States
ALLCUTIS Research
Portsmouth, New Hampshire, 03801, United States
Icahn Sch of Med at Mt. Sinai
New York, New York, 10029, United States
Sadick Research Group
New York, New York, 10075, United States
Wake Research Associates
Raleigh, North Carolina, 27612, United States
Lynn Health Science Institute
Oklahoma City, Oklahoma, 73112, United States
Vital Prospects Clinical Research Institute, P.C.
Tulsa, Oklahoma, 74136, United States
Clinical Research Institute
Medford, Oregon, 97504, United States
Oregon Medical Research Center
Portland, Oregon, 97223, United States
Clinical Partners, LLC
Johnston, Rhode Island, 02919, United States
Bellaire Dermatology
Bellaire, Texas, 77401, United States
Progressive Clinical Research
San Antonio, Texas, 78213, United States
Premier Clinical Research
Spokane, Washington, 99202, United States
The St. George Hospital
Kogarah, New South Wales, 2217, Australia
Holdsworth House Medical Practice
Sydney, New South Wales, 2010, Australia
Skin & Cancer Foundation Australia
Westmead, New South Wales, 2145, Australia
The Skin Centre
Benowa, Queensland, 4217, Australia
Veracity Clinical Research Pty Ltd
Woolloongabba, Queensland, 4102, Australia
Eastern Clinical Research Unit
Box Hill, Victoria, 3128, Australia
Emeritus Research
Camberwell, Victoria, 3124, Australia
Skin Health Institute Inc.
Carlton, Victoria, 3053, Australia
Sinclair Dermatology
East Melbourne, Victoria, 3002, Australia
Fremantle Dermatology
Fremantle, Western Australia, 6160, Australia
Burswood Dermatology
Victoria Park, Western Australia, 06100, Australia
CARe Clinic
Red Deer, Alberta, T4P1K4, Canada
CCA Medical Research
Ajax, Ontario, L1S7K8, Canada
Skin Health
Cobourg, Ontario, K9A 0Z4, Canada
Dermatology and Dermatologic Surgery
Ottawa, Ontario, K2G6E2, Canada
The Centre for Dermatology
Richmond Hill, Ontario, L4B 1A5, Canada
Kliiniliste uuringute Keskus OU
Tartu, 50160, Estonia
Hopital Saint-Louis
Paris, Cedex 10, 75475, France
CHU de Bordeaux Hopital Saint Andre
Bordeaux, 33075, France
CHU DIJON - Hopital le Bocage
Dijon, 21079, France
Cabinet MĂ©dical
Martigues, 13500, France
Hopital Larrey
Toulouse, 31059, France
Clinic of Dermatology and STD
Riga, LV-1001, Latvia
Health Center 4, Affiliate Diagnostic Center
Riga, LV-1003, Latvia
Health and Aesthetics LTD
Riga, LV-1009, Latvia
Latvian Dermatology Institute
Riga, LV-1011, Latvia
Smite Aija - Practice in Dermatology Venereology
Talsi, LV-3201, Latvia
JSC "CD8 Alergology Clinic"
Kaunas, LT-44192, Lithuania
Hospital of Lithuanian University of Health Sciences Kauno klinikos
Kaunas, LT-50161, Lithuania
Jsc Renmeda
Vilnius, LT-07195, Lithuania
JSC "Center for Diagnosis and Treatment of Allergic Diseases"
Vilnius, LT-08109, Lithuania
Children's Hospital, Affiliate of Vilnius University Hospital Santaros klinikos
Vilnius, LT-08406, Lithuania
Inlita (Santaros CTC)
Vilnius, LT-08406, Lithuania
Vilnius University Hospital Santaros klinikos
Vilnius, LT-08441, Lithuania
Diamond Clinic
Krakow, Lesser Poland Voivodeship, 31-559, Poland
Alergo-Med Specjalistyczna Przychodnia Lekarska Sp Z O.O.
TarnĂ³w, Malopolska, 33100, Poland
Centralny Szpital Kliniczny MSWiA
Warsaw, Masovian Voivodeship, 02-507, Poland
Zespol Naukowo - Leczniczy "Iwolang" Sp. z o.o.
Iwonicz-ZdrĂ³j, Podkarpackie Voivodeship, 38-440, Poland
Centrum Medyczne Angelius Provita
Katowice, Silesian Voivodeship, 40-611, Poland
Twoja Przychodnia - Szczecinskie Centrum Medyczne
Szczecin, West Pomeranian Voivodeship, 71-434, Poland
GynCentrum Sp z o.o.
Katowice, 40-851, Poland
Specjalistyczny Osrodek Alergologiczno-Internistyczny ALL-ME
Krakow, 31-023, Poland
Samodzielny Publiczny Szpital Kliniczny nr 1
Lublin, 20-081, Poland
Centrum Alergologii Teresa Hofman
Poznan, 60-214, Poland
Clinical Research Group Sp. z o.o.
Warsaw, 01-142, Poland
CityClinic Przychodnia Lekarsko-Psychologiczna
Wroclaw, 50-566, Poland
Korea University Ansan Hospital
Ansan-si, Gyeonggi-do, 15355, South Korea
Pusan National University Hospital
Pusan, Korea, 49241, South Korea
Hanyang University Medical Center
Seoul, Korea, 04763, South Korea
Ulsan University Hospital
Ulsan, Korea, 44033, South Korea
Ajou University Hospital
Suwon, Kyung Gi-Do, Korea, 16499, South Korea
Soon Chun Hyang University Seoul Hospital
Seoul, Yongsan-gu, 04401, South Korea
Incheon St. Mary's Hospital
Incheon, 21431, South Korea
Severance Hospital
Seoul, 03722, South Korea
Konkuk University Medical Center
Seoul, 05030, South Korea
Chungang University Hospital
Seoul, 06973, South Korea
Hallym University Kangnam Sacred Heart Hospital
Seoul, 07441, South Korea
Sant Joan de Deu Serveis En Salut Mental
SANT BOI de Llobrega, Barcelona, 08830, Spain
Hospital De Basurto
Bilbao, Vizcaya, 48013, Spain
Hospital General Universitario Alicante
Alicante, 03010, Spain
Hospital Germans Trias i Pujol
Badalona, 08916, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041, Spain
Hospital Infanta Leonor
Madrid, 28031, Spain
Hospital Universitario Virgen Macarena
Seville, 41009, Spain
Related Publications (11)
Sher ER, Golant A, de Bruin-Weller M, Carrascosa JM, Mehta V, Bieber T, Dawson Z, Atwater AR, Zhong J, Rodriguez Calleja L, Boguniewicz M. Lebrikizumab is efficacious in adults and adolescents with moderate-to-severe atopic dermatitis regardless of atopic comorbidities. Ann Allergy Asthma Immunol. 2025 Dec 21:S1081-1206(25)01389-4. doi: 10.1016/j.anai.2025.12.017. Online ahead of print.
PMID: 41435984DERIVEDSilverberg JI, Wollenberg A, Stein Gold L, Yosipovitch G, Lio P, Vestergaard C, Stander S, Carrascosa JM, Gallo G, Casillas M, Ding Y, Yang FE, Pierce E, Agell H, Del Rosso J. Lebrikizumab provides stable skin response with no or minimal fluctuations for up to 2 years in patients with atopic dermatitis. Clin Exp Dermatol. 2025 Nov 8:llaf490. doi: 10.1093/ced/llaf490. Online ahead of print.
PMID: 41206702DERIVEDGuttman-Yassky E, Sun Z, Mena LR, Hahn N, Nickoloff BJ, Preuss C, Siu K, Natalie CR, Gallo G, Wolf E, Eyerich K, Aparici M, Benschop RJ, Okragly A. Lebrikizumab Rapidly Lowers Inflammatory Biomarkers with Clinical Correlations in Moderate-to-Severe Atopic Dermatitis. Dermatol Ther (Heidelb). 2025 Sep;15(9):2595-2614. doi: 10.1007/s13555-025-01481-4. Epub 2025 Jul 15.
PMID: 40663228DERIVEDSimpson E, Fernandez-Penas P, de Bruin-Weller M, Lio PA, Chu CY, Ezzedine K, Agell H, Casillas M, Ding Y, Yang FE, Pierce E, Bieber T. Improvement Across Dimensions of Disease with Lebrikizumab Use in Atopic Dermatitis: Two Phase 3, Randomized, Double-Blind, Placebo-Controlled Monotherapy Trials (ADvocate1 and ADvocate2). Adv Ther. 2025 Jan;42(1):132-143. doi: 10.1007/s12325-024-02974-y. Epub 2024 Sep 9.
PMID: 39249591DERIVEDSilverberg JI, Wollenberg A, Stein Gold L, Del Rosso J, Yosipovitch G, Lio P, Carrascosa JM, Gallo G, Ding Y, Xu Z, Casillas M, Pierce E, Agell H, Stander S. Patients with Moderate-to-Severe Atopic Dermatitis Maintain Stable Response with No or Minimal Fluctuations with 1 Year of Lebrikizumab Treatment. Dermatol Ther (Heidelb). 2024 Aug;14(8):2249-2260. doi: 10.1007/s13555-024-01226-9. Epub 2024 Aug 10.
PMID: 39123054DERIVEDYosipovitch G, Lio P, Legat FJ, Chovatiya R, Deleuran M, Pierce E, Casillas M, Ding Y, Yang FE, Bardolet L, Stander S. Stable Response and Sustained Improvement of Itch and Sleep Symptoms in Patients with Atopic Dermatitis Treated with Lebrikizumab over 52 Weeks. Dermatol Ther (Heidelb). 2024 Aug;14(8):2171-2180. doi: 10.1007/s13555-024-01225-w. Epub 2024 Jul 13.
PMID: 39002092DERIVEDLio PA, Armstrong A, Gutermuth J, Nosbaum A, Sofen H, Gil EG, Casillas M, Chen S, Sun L, Pierce E, Elmaraghy H, Dawson Z, Torres T. Lebrikizumab Improves Quality of Life and Patient-Reported Symptoms of Anxiety and Depression in Patients with Moderate-to-Severe Atopic Dermatitis. Dermatol Ther (Heidelb). 2024 Jul;14(7):1929-1943. doi: 10.1007/s13555-024-01199-9. Epub 2024 Jun 26.
PMID: 38922484DERIVEDSimpson EL, de Bruin-Weller M, Hong HC, Staumont-Salle D, Blauvelt A, Eyerich K, Gooderham M, Shahriari M, Mallbris L, Atwater AR, Rueda MJ, Ding Y, Liu Z, Agell H, Silverberg JI. Lebrikizumab Provides Rapid Clinical Responses Across All Eczema Area and Severity Index Body Regions and Clinical Signs in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis. Dermatol Ther (Heidelb). 2024 May;14(5):1145-1160. doi: 10.1007/s13555-024-01158-4. Epub 2024 May 3.
PMID: 38700646DERIVEDSoung J, Stander S, Gutermuth J, Pau-Charles I, Dawson Z, Yang FE, Sun L, Pierce E, Elmaraghy H, Stein-Gold L. Lebrikizumab monotherapy impacts on quality of life scores through improved itch and sleep interference in two Phase 3 trials. J Dermatolog Treat. 2024 Dec;35(1):2329240. doi: 10.1080/09546634.2024.2329240. Epub 2024 Apr 28.
PMID: 38679419DERIVEDBlauvelt A, Thyssen JP, Guttman-Yassky E, Bieber T, Serra-Baldrich E, Simpson E, Rosmarin D, Elmaraghy H, Meskimen E, Natalie CR, Liu Z, Xu C, Pierce E, Morgan-Cox M, Garcia Gil E, Silverberg JI. Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: 52-week results of two randomized double-blinded placebo-controlled phase III trials. Br J Dermatol. 2023 May 24;188(6):740-748. doi: 10.1093/bjd/ljad022.
PMID: 36994947DERIVEDSilverberg JI, Guttman-Yassky E, Thaci D, Irvine AD, Stein Gold L, Blauvelt A, Simpson EL, Chu CY, Liu Z, Gontijo Lima R, Pillai SG, Seneschal J; ADvocate1 and ADvocate2 Investigators. Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis. N Engl J Med. 2023 Mar 23;388(12):1080-1091. doi: 10.1056/NEJMoa2206714. Epub 2023 Mar 15.
PMID: 36920778DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical officer
- Organization
- Eli Lilly and Company
Study Officials
- STUDY DIRECTOR
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Double-blind
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 29, 2019
First Posted
October 31, 2019
Study Start
September 24, 2019
Primary Completion
June 21, 2021
Study Completion
May 3, 2022
Last Updated
November 30, 2022
Results First Posted
August 29, 2022
Record last verified: 2022-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
- Access Criteria
- A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.