Evaluation of the Efficacy and Safety of Lebrikizumab (LY3650150) in Moderate to Severe Atopic Dermatitis
ADvocate2
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
445
8 countries
89
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 Oct 2019
89 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
October 29, 2019
CompletedFirst Submitted
Initial submission to the registry
November 25, 2019
CompletedFirst Posted
Study publicly available on registry
November 26, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 12, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
April 28, 2022
CompletedResults Posted
Study results publicly available
September 16, 2022
CompletedMay 24, 2023
April 1, 2023
1.7 years
November 25, 2019
July 11, 2022
April 24, 2023
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 AD - disease extent and clinical signs 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 score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI-75 responder is defined as a participant who achieves a ≥ 75% reduction 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
Baseline to Week 16
Percentage of Participants Achieving EASI-90 (≥90% Reduction in EASI Score) From Baseline to Week 16
Baseline to Week 16
Percentage 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 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 and one placebo SC injection as maintenance loading dose on Week 16 and Week 18. One 250 mg Lebrikizumab SC injection Q2W until Week 50.
Lebrikizumab Q4W
EXPERIMENTALMaintenance Period (Week 16-Week 52): One 250 mg Lebrikizumab SC injection and one placebo SC injection as maintenance loading dose on Week 16 and two placebo SC injections on Week 18. 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.
Escape Arm (Lebrikizumab Q2W)
EXPERIMENTALMaintenance Period (Week 16-Week 52): Participants who require topical or systemic rescue treatment for atopic dermatitis during the Induction Period, or are non-responders at Week 16, will be eligible for treatment in an Escape Arm where participants will receive open-label lebrikizumab Q2W from Week 16 through Week 52. In addition, participants who do not maintain an acceptable response during the Maintenance Period (have an EASI score \<50% of baseline), will be eligible for the Escape Arm.
Interventions
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 (89)
Investigate MD
Scottsdale, Arizona, 85255, United States
Northwest Arkansas Clinical Trials Center
Rogers, Arkansas, 72758, United States
Bakersfield Dermatology and Skin Cancer Medical Group
Bakersfield, California, 93309, United States
Center For Dermatology Clinical Research, Inc.
Fremont, California, 94538, United States
Woodward Centre
Fresno, California, 93720, United States
Dermatology Research Associates
Los Angeles, California, 90045, United States
LA Universal Research Center, INC
Los Angeles, California, 90057, United States
University Clinical Trials, Inc.
San Diego, California, 92123, United States
San Luis Dermatology & Laser Clinic
San Luis Obispo, California, 93405, United States
Clinical Physiology Associates, Clinical Study Center
Fort Myers, Florida, 33916-9452, United States
Direct Helpers Medical Center
Hialeah, Florida, 33012, United States
The Community Research of South Florida
Hialeah, Florida, 33016, United States
Solutions Through Advanced Research, Inc.
Jacksonville, Florida, 32256, United States
Georgia Pollens Clinical Research Centers, Inc
Albany, Georgia, 31707, United States
Marietta Dermatology Clinical Research
Marietta, Georgia, 30060, United States
Advanced Medical Research
Sandy Springs, Georgia, 30328, United States
Arlington Dermatology
Rolling Meadows, Illinois, 60008, United States
NorthShore University HealthSystem
Skokie, Illinois, 60077, United States
Kansas City Dermatology, PA
Overland Park, Kansas, 66215, United States
Meridian Clinical Research
Baton Rouge, Louisiana, 70808, United States
ActivMed Practices and Research
Beverly, Massachusetts, 01915, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Great Lakes Research Group, Inc.
Bay City, Michigan, 48706, United States
Clarkston Skin Research
Clarkston, Michigan, 48346, United States
Associated Skin Care Specialists
Fridley, Minnesota, 55432, United States
Central Dermatology PC
St Louis, Missouri, 63117, United States
Forest Hills Dermatology Group
Kew Gardens, New York, 11415, United States
OnSite Clinical Solutions
Charlotte, North Carolina, 28277, United States
Wilmington Dermatology Center
Wilmington, North Carolina, 28405, United States
Dermatology and Skin Surgery Center
Exton, Pennsylvania, 19341, United States
DermDOX
Hazleton, Pennsylvania, 18201, United States
Peak Research LLC
Upper Saint Clair, Pennsylvania, 15241, United States
Dermatology & Laser Center of Charleston
Charleston, South Carolina, 29407, United States
Palmetto Clinical Trial Services
Greenville, South Carolina, 29601, United States
Arlington Research Center, Inc
Arlington, Texas, 76011, United States
Innovate Research, LLC
Fort Worth, Texas, 76244, United States
Austin Institute for Clinical Research
Pflugerville, Texas, 78660, United States
University of Utah MidValley Dematology
Murray, Utah, 84107, United States
Virginia Clinical Research, Inc.
Norfolk, Virginia, 23502, United States
Dermatology Associates
Seattle, Washington, 98101, United States
DCC Sveti Georgi
Plovdiv, 4000, Bulgaria
Diagnostic and Consultation Center 14
Sofia, 1408, Bulgaria
Alexandrovska University Hospital
Sofia, 1432, Bulgaria
Euro Derma clinic
Sofia, 1606, Bulgaria
Military Medical Academy
Sofia, 1606, Bulgaria
Medical centre Alitera-Med EOOD
Sofia, 1618, Bulgaria
Dr. Chih-ho Hong Medical Inc.
Surrey, British Columbia, V3R 6A7, Canada
Simcoderm Medical & Surgical Dermatology Centre
Barrie, Ontario, L4M 7G1, Canada
Lynderm Research Inc.
Markham, Ontario, L3P1X2, Canada
North York Research Inc.
North York, Ontario, M2M4J5, Canada
Ottawa Allergy Research Corp
Ottawa, Ontario, K1G 6C6, Canada
K. Papp Clinical Research
Waterloo, Ontario, N2J 1C4, Canada
Derma-Study-Center Friedrichshafen GmbH
Friedrichshafen, Baden-Wurttemberg, 88045, Germany
Studienzentrum Dr.Beate Schwarz
Langenau, Baden-Wurttemberg, 89129, Germany
Hautarztpraxis am Löwenmarkt
Stuttgart, Baden-Wurttemberg, 70499, Germany
licca Fachklinik
Augsburg, Bavaria, 86179, Germany
Rosenpark Research Geschäftsbereich der Rosenparkklinik GmbH
Darmstadt, Hesse, 64283, Germany
Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
Frankfurt am Main, Hesse, 60590, Germany
Elbe Klinikum Buxtehude
Buxtehude, Lower Saxony, 21614, Germany
Klinische Forschung Osnabrück
Osnabrück, Lower Saxony, 49074, Germany
Fachklinik Bad Bentheim
Bad Bentheim, North Rhine-Westphalia, 48455, Germany
Hautzentrum im Jahrhunderthaus
Bochum, North Rhine-Westphalia, 44793, Germany
Universitätsklinikum Münster
Münster, North Rhine-Westphalia, 48149, Germany
SIBAmed Studienzentrum GmbH & Co. KG
Leipzig, Saxony, 04103, Germany
Universität Leipzig - Universitätsklinikum
Leipzig, Saxony, 04103, Germany
Universitätsklinikum Schleswig-Holstein
Lübeck, Schleswig-Holstein, 23538, Germany
Praxis Dr. Michael Dietlen
Augsburg, 86150, Germany
Charité Universitätsmedizin Berlin Campus Buch
Berlin, 10117, Germany
ISA GmbH
Berlin, 10789, Germany
Praxis für Ganzheitliche Dermatologie im Ärztehaus
Berlin, 13055, Germany
Universitätsklinikum Hamburg
Hamburg, 20246, Germany
TFS Trial Form Support GmbH
Hamburg, 20537, Germany
Clinica De Enfermedades Cronicas y Procedimientos Especiales
Morelia, Michoacan Morelia, CP 58249, Mexico
Derma Norte del Bajío, S.C.
Aguascalientes, 20130, Mexico
National University Hospital
Singapore, 119074, Singapore
Singapore General Hospital
Singapore, 169078, Singapore
Kk Women'S and Childrens Hospital
Singapore, 229899, Singapore
National Skin Centre NSC
Singapore, 308205, Singapore
Kaohsiung Chang Gung Memorial Hospital
Niaosong Dist, Kaohsiung City, 833, Taiwan
Kaohsiung Medical University Chung-Ho Institutional Review B
Kaohsiung City, 807, Taiwan
Taipei Medical University- Shuang Ho Hospital
New Taipei City, 235, Taiwan
Chung Shan Medical University Hospital
Taichung, 402, Taiwan
China Medical University Hospital
Taichung, 40447, Taiwan
National Taiwan University Hospital
Taipei, 10002, Taiwan
Chang Gung Memorial Hospital - Linkou
Taoyuan, 33305, Taiwan
Municipal Healthcare Institution Kharkiv City Dermatoverenologic Dispensary N2
Kharkiv, 61038, Ukraine
Rivne Regional Dermatology and Venereology Dispensary
Rivne, 39028, Ukraine
Treatment-diagnostic center PE "Asclepius"
Uzhhorod, 88002, Ukraine
Community Institution Zaporizhzhya Regional Dermatovenereology Clinical Hospital of Zaporizhzhya Regional Council
Zaporizhzhya, 69000, Ukraine
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)
Limitations and Caveats
One investigational site with eighteen participants was excluded from analysis due to GCP issues.
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
November 25, 2019
First Posted
November 26, 2019
Study Start
October 29, 2019
Primary Completion
July 12, 2021
Study Completion
April 28, 2022
Last Updated
May 24, 2023
Results First Posted
September 16, 2022
Record last verified: 2023-04
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.