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.

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.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Other: Placebo; Biological: Lebrikizumab

• Study Type: Interventional
• Enrollment (Actual): 445
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • DCC Sveti Georgi
  • Sofia, Bulgaria, 1606
    • Military Medical Academy
  • Sofia, Bulgaria, 1408
    • Diagnostic and Consultation Center 14
  • Sofia, Bulgaria, 1606
    • Euro Derma clinic
  • Sofia, Bulgaria, 1618
    • Medical centre Alitera-Med EOOD
  • Sofia, Bulgaria, 1432
    • Alexandrovska University Hospital
• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3R 6A7
      • Dr. Chih-Ho Hong Medical Inc.
  • Ontario
    • Barrie, Ontario, Canada, L4M 7G1
      • Simcoderm Medical & Surgical Dermatology Centre
    • Markham, Ontario, Canada, L3P1X2
      • Lynderm Research Inc.
    • North York, Ontario, Canada, M2M4J5
      • North York Research Inc.
    • Ottawa, Ontario, Canada, K1G 6C6
      • Ottawa Allergy Research Corp
    • Waterloo, Ontario, Canada, N2J 1C4
      • K. Papp Clinical Research
• Germany
  • Augsburg, Germany, 86150
    • Praxis Dr. Michael Dietlen
  • Berlin, Germany, 10789
    • ISA GmbH
  • Berlin, Germany, 13055
    • Praxis für Ganzheitliche Dermatologie im Ärztehaus
  • Berlin, Germany, 10117
    • Charité Universitätsmedizin Berlin Campus Buch
  • Hamburg, Germany, 20537
    • TFS Trial Form Support GmbH
  • Hamburg, Germany, 20246
    • Universitatsklinikum Hamburg
  • Baden-Württemberg
    • Friedrichshafen, Baden-Württemberg, Germany, 88045
      • Derma-Study-Center Friedrichshafen Gmbh
    • Langenau, Baden-Württemberg, Germany, 89129
      • Studienzentrum Dr.Beate Schwarz
    • Stuttgart, Baden-Württemberg, Germany, 70499
      • Hautarztpraxis am Löwenmarkt
  • Bayern
    • Augsburg, Bayern, Germany, 86179
      • Licca Fachklinik
  • Hessen
    • Darmstadt, Hessen, Germany, 64283
      • Rosenpark Research Geschäftsbereich der Rosenparkklinik GmbH
    • Frankfurt am Main, Hessen, Germany, 60590
      • Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
  • Niedersachsen
    • Buxtehude, Niedersachsen, Germany, 21614
      • Elbe Klinikum Buxtehude
    • Osnabrück, Niedersachsen, Germany, 49074
      • Klinische Forschung Osnabrück
  • Nordrhein-Westfalen
    • Bad Bentheim, Nordrhein-Westfalen, Germany, 48455
      • Fachklinik Bad Bentheim
    • Bochum, Nordrhein-Westfalen, Germany, 44793
      • Hautzentrum im Jahrhunderthaus
    • Münster, Nordrhein-Westfalen, Germany, 48149
      • Universitätsklinikum Münster
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Universität Leipzig - Universitätsklinikum
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • SIBAmed Studienzentrum GmbH & Co. KG
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Universitätsklinikum Schleswig-Holstein
• Mexico
  • Aguascalientes, Mexico, 20130
    • Derma Norte del Bajío, S.C.
  • Michoacan Morelia
    • Morelia, Michoacan Morelia, Mexico, CP 58249
      • Clinica De Enfermedades Cronicas y Procedimientos Especiales
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore, 169078
    • Singapore General Hospital
  • Singapore, Singapore, 229899
    • Kk Women'S and Childrens Hospital
  • Singapore, Singapore, 308205
    • National Skin Centre NSC
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Institutional Review B
  • New Taipei City, Taiwan, 235
    • Taipei Medical University- Shuang Ho Hospital
  • Taichung, Taiwan, 402
    • Chung Shan Medical University Hospital
  • Taichung City, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taoyuan City, Taiwan, 33305
    • Chang Gung Memorial Hospital - Linkou
  • Kaohsiung City
    • Niaosong Dist, Kaohsiung City, Taiwan, 833
      • Kaohsiung Chang Gung Memorial Hospital
• Ukraine
  • Kharkiv, Ukraine, 61038
    • Municipal Healthcare Institution Kharkiv City Dermatoverenologic Dispensary N2
  • Rivne, Ukraine, 39028
    • Rivne Regional Dermatology and Venereology Dispensary
  • Uzhhorod, Ukraine, 88002
    • Treatment-diagnostic center PE "Asclepius"
  • Zaporizhzhya, Ukraine, 69000
    • Community Institution Zaporizhzhya Regional Dermatovenereology Clinical Hospital of Zaporizhzhya Regional Council
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85255
      • Investigate MD
  • Arkansas
    • Rogers, Arkansas, United States, 72758
      • Northwest Arkansas Clinical Trials Center
  • California
    • Bakersfield, California, United States, 93309
      • Bakersfield Dermatology and Skin Cancer Medical Group
    • Fremont, California, United States, 94538
      • Center for Dermatology Clinical Research, Inc.
    • Fresno, California, United States, 93720
      • Woodward Centre
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
    • Los Angeles, California, United States, 90057
      • LA Universal Research Center, INC
    • San Diego, California, United States, 92123
      • University Clinical Trials, Inc.
    • San Luis Obispo, California, United States, 93405
      • San Luis Dermatology & Laser Clinic
  • Florida
    • Fort Myers, Florida, United States, 33916-9452
      • Clinical Physiology Associates, Clinical Study Center
    • Hialeah, Florida, United States, 33012
      • Direct Helpers Medical Center
    • Hialeah, Florida, United States, 33016
      • The Community Research of South Florida
    • Jacksonville, Florida, United States, 32256
      • Solutions Through Advanced Research, Inc.
  • Georgia
    • Albany, Georgia, United States, 31707
      • Georgia Pollens Clinical Research Centers, Inc
    • Marietta, Georgia, United States, 30060
      • Marietta Dermatology Clinical Research
    • Sandy Springs, Georgia, United States, 30328
      • Advanced Medical Research
  • Illinois
    • Rolling Meadows, Illinois, United States, 60008
      • Arlington Dermatology
    • Skokie, Illinois, United States, 60077
      • NorthShore University HealthSystem
  • Kansas
    • Overland Park, Kansas, United States, 66215
      • Kansas City Dermatology, PA
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Meridian Clinical Research
  • Massachusetts
    • Beverly, Massachusetts, United States, 01915
      • ActivMed Practices and Research
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Great Lakes Research Group, Inc.
    • Clarkston, Michigan, United States, 48346
      • Clarkston Skin Research
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Associated Skin Care Specialists
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Central Dermatology PC
  • New York
    • Kew Gardens, New York, United States, 11415
      • Forest Hills Dermatology Group
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • OnSite Clinical Solutions
    • Wilmington, North Carolina, United States, 28405
      • Wilmington Dermatology Center
  • Pennsylvania
    • Exton, Pennsylvania, United States, 19341
      • Dermatology and Skin Surgery Center
    • Hazleton, Pennsylvania, United States, 18201
      • DermDox
    • Upper Saint Clair, Pennsylvania, United States, 15241
      • Peak Research LLC
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Dermatology & Laser Center of Charleston
    • Greenville, South Carolina, United States, 29601
      • Palmetto Clinical Trial Services
  • Texas
    • Arlington, Texas, United States, 76011
      • Arlington Research Center, Inc
    • Fort Worth, Texas, United States, 76244
      • Innovate Research, LLC
    • Pflugerville, Texas, United States, 78660
      • Austin Institute for Clinical Research
  • Utah
    • Murray, Utah, United States, 84107
      • University of Utah MidValley Dematology
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Clinical Research, Inc.
  • Washington
    • Seattle, Washington, United States, 98101
      • Dermatology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Induction 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.	Other: Placebo; Subcutaneous Injection
Experimental: Lebrikizumab Q2W; Induction 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.	Biological: Lebrikizumab; Subcutaneous injection; Other Names: LY3650150; DRM06
Experimental: Lebrikizumab Q4W; 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 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.	Other: Placebo; Subcutaneous Injection; Biological: Lebrikizumab; Subcutaneous injection; Other Names: LY3650150; DRM06
Experimental: Escape Arm (Lebrikizumab Q2W); Maintenance 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.	Biological: Lebrikizumab; Subcutaneous injection; Other Names: LY3650150; DRM06

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 2	The IGA measures the investigator's global assessment of the participant's overall severity of their 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 2
Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 4	The IGA measures the investigator's global assessment of the participant's overall severity of their 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 4
Percentage of Participants With a Pruritus NRS Score of ≥4-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."	Baseline to Week 16
Percentage of Participants With a Pruritus NRS Score of ≥5-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."	Baseline to Week 16
Change From Baseline in Percent Body Surface Area (BSA) at Week 16	The BSA affected by AD will be assessed for 4 separate body regions: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. BSA was calculated using the participant's palm using the 1% rule, 1 palm was equivalent to 1% with estimates of the number of palms it takes to cover the affected AD area. Maximum number of palms were 10 palms for head and neck (10%), 20 palms for upper extremities (20%), 30 palms for trunk, including axilla and groin (30%), 40 palms for lower extremities, including buttocks (40%). Percent of BSA for a body region was calculated as = total number of palms in a body region * % surface area equivalent to 1 palm. Overall percent BSA of all 4 body regions ranges from 0% to 100 % with higher values representing greater severity of AD.	Baseline, Week 16
Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16	The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment, over the previous week. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life. LS Mean was calculated using the ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.	Baseline, Week 16
Percentage of Participants With a DLQI Total Score of ≥4-point at Baseline Achieving ≥4-point Improvement in DLQI From Baseline to Week 16	The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment, over the previous week. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life.	Baseline to Week 16
Change From Baseline in Sleep-loss Score at Week 16	Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale [0 (not at all) to 4 (unable to sleep at all)]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary. LS Mean was calculated using ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.	Baseline, Week 16
Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."	Baseline to Week 1
Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."	Baseline to Week 2
Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."	Baseline to Week 4
Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."	Baseline to Week 1
Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."	Baseline to Week 2
Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."	Baseline to Week 4
Percentage of Participants From Those With a Pruritus NRS of ≥4-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."	Baseline to Week 52
Percentage of Participants From Those With a Pruritus NRS of ≥5-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."	Baseline to Week 52
Change From Baseline in EQ-5D-5L at Week 16 - Visual Analog Scale (VAS)	The EQ-5D-5L is a 2-part measurement. The second part is assessed using a VAS that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.	Baseline, Week 16
Percentage Change in Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable." Least Squares (LS) Mean was calculated using analysis of covariance (ANCOVA) model with treatment and randomization strata (region, disease severity, age) as fixed factors and baseline value as covariate.	Baseline, Week 16
Percentage of Participants Achieving ≥4-point Improvement in DLQI From Baseline to Week 16	The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment, over the previous week. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life.	Baseline to Week 16
Percentage Change in Sleep-loss Score From Baseline to Week 16	Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale [0 (not at all) to 4 (unable to sleep at all)]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary. LS Mean was calculated using ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.	Baseline, Week 16
Percentage of Participants With a Sleep-loss Score ≥2 Points at Baseline Who Achieve a ≥2 Points Reduction From Baseline to Week 16	Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale [0 (not at all) to 4 (unable to sleep at all)]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary.	Baseline to Week 16
Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16	POEM is a 7-item, validated, questionnaire used by the participant to assess disease symptoms over the last week. The participant is asked to respond to 7 questions on skin dryness, itching, flaking, cracking, sleep loss, bleeding and weeping. All 7 answers carry equal weight with a total possible score from 0 to 28 (answers scored as: No days=0; 1-2 days = 1; 3-4 days = 2; 5-6 days = 3; everyday = 4). A high score is indicative of a poor quality of life. POEM responses will be captured using an electronic diary and transferred into the clinical database. LS Mean was calculated using MMRM model using treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit as covariates, geographic region, age group, baseline IGA (3 versus 4) score as fixed.	Baseline, Week 16
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety at Week 16-Adolescents	PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.	Baseline, Week 16
Change From Baseline in PROMIS Anxiety at Week 16 - Adults	PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.	Baseline, Week 16
Change From Baseline in PROMIS Depression at Week 16- Adolescents	PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.	Baseline, Week 16
Change From Baseline in PROMIS Depression at Week 16- Adults	PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.	Baseline, Week 16
Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 16 in Participants Who Have Self-reported Comorbid Asthma	The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze) enquire about the frequency and/or severity of symptoms over the previous week. The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/ limitation) scale. The ACQ-5 score is the average of the individual item scores and ranges from 0 (totally controlled) to 6 (severely uncontrolled). Higher scores indicate lower asthma control. LS Mean was calculated using ANCOVA with treatment, geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.	Baseline, Week 16
Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16	The CDLQI questionnaire is designed for use in children (4 to 16 years of age). It consists of 10 items that are grouped into 6 domains: symptoms & feelings, leisure, school or holidays, personal relationships, sleep, & treatment. The scoring of each question is: Very much =3; Quite a lot = 2; Only a little = 1; Not at all = 0. CDLQI total score is calculated by summing all 10 items responses, and has a range of 0 to 30 (higher scores are indicative of greater impairment). LS Mean was calculated using MMRM model which includes treatment, baseline value, visit, the interaction of the baseline value-by-visit as covariates, the interaction of treatment by-visit, geographic region, age group, and baseline IGA (3 versus 4) score as fixed factors.	Baseline, Week 16
Percentage of Participants With an 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 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 EASI-90 (≥90% 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-90 responder is defined as a participant who achieves a ≥ 90% reduction from baseline in the EASI score.	Baseline to Week 16
Percentage Change 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). LS Mean was calculated using ANCOVA model with treatment, stratification factors of geographic region, age group, baseline IGA score (IGA 3 versus 4) as fixed factors baseline value as covariate.	Baseline, Week 16
Percentage of Participants Achieving EASI-90 From Baseline to Week 4	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-90 responder is defined as a participant who achieves a ≥ 90% reduction from baseline in the EASI score.	Baseline to Week 4
Percentage Change in SCORing Atopic Dermatitis (SCORAD) From Baseline to Week 16	SCORAD is validated tool for assessing the extent and intensity of AD, it consists of 3 components: A=extent of AD as a percentage of each defined body area and reported as sum of all areas, with maximum score of 100%. B=severity of 6 specific symptoms of AD (redness, swelling, oozing/crusting, excoriation, skin thickening/lichenification, dryness) assessed using following scale: none=0, mild=1, moderate=2, or severe=3 for maximum of 18 total points. C=subjective assessment of itch and sleeplessness recorded by participant on visual analog scale (VAS), where 0=no itch/no sleeplessness and 10=worst imaginable itch/sleeplessness with maximum score of 20. SCORAD total score is calculated: A/5+7*B/2+ C to give total score range of 0 to 103, where 0=no disease to 103=severe disease. LS Mean was calculated using ANCOVA model with treatment group and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.	Baseline, Week 16
Pharmacokinetics (PK): Trough Serum Concentrations of Lebrikizumab in Maintenance Period (C-trough)	C-trough was the concentration of study drug in the blood immediately before the next dose was administered. Trough serum concentration of Lebrikizumab was assessed at predose week 52.	Predose at Week 52
Percentage of Participants From Those Re-randomized Having Achieved EASI-75 at Week 16 Who Continue to Exhibit EASI-75 at Week 52 (EASI-75 Calculated Relative to Baseline EASI Score)	The EASI assesses objective physician estimates of 2 dimensions of AD - 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% reduction from baseline in the EASI score.	Baseline to Week 52
Percentage of Participants From Those Re-randomized Having Achieved IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 16 Who Continue to Exhibit an IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 52	The IGA measures the investigator's global assessment of the participant's overall severity of their 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 52
Percentage Change in SCORAD (From Those Re-randomized Having Achieved EASI-75 at Week 16) From Baseline at Week 52	SCORAD is a validated tool for assessing the extent and intensity of AD, it consists of 3 components: A=extent of AD as a percentage of each defined body area and reported as sum of all areas, with maximum score of 100%. B=severity of 6 specific symptoms of AD (redness, swelling, oozing/crusting, excoriation, skin thickening/lichenification, dryness) assessed using following scale: none=0, mild=1, moderate=2, or severe=3 for maximum of 18 total points. C=subjective assessment of itch and sleeplessness recorded by participant on VAS, where 0=no itch/no sleeplessness and 10=worst imaginable itch/sleeplessness with maximum score of 20. SCORAD total score is calculated: A/5+7*B/2+ C to give total score range of 0 to 103, where 0=no disease to 103=severe disease. LS Mean was calculated using ANCOVA model with treatment group and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.	Baseline, Week 52
Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 16 - Health State Index	The European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a is a 2-part questionnaire which measure health status of the participant. The first component (Health state) is a descriptive system of the respondent's health comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1. A higher score indicates better health state. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.	Baseline, Week 16

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Dermira, Inc.
• Investigators: 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

Publications and helpful links

Helpful Links

• Evaluation of the Efficacy and Safety of Lebrikizumab (LY3650150) in Moderate to Severe Atopic Dermatitis (ADvocate2)

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2019
• Primary Completion (Actual): July 12, 2021
• Study Completion (Actual): April 28, 2022

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: November 25, 2019
• First Posted (Actual): November 26, 2019

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Eczema; Dermatitis, Atopic; Skin Diseases; Dermatitis
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: 17802; 2019-002933-12 (EudraCT Number); J2T-DM-KGAC (Other Identifier: Eli Lilly and Company); DRM06-AD05 (Other Identifier: Dermira, Inc)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing 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.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No