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

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): 424
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • The St. George Hospital
    • Sydney, New South Wales, Australia, 2010
      • Holdsworth House Medical Practice
    • Westmead, New South Wales, Australia, 2145
      • Skin & Cancer Foundation Australia
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • The Skin Centre
    • Woolloongabba, Queensland, Australia, 4102
      • Veracity Clinical Research Pty Ltd
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Clinical Research Unit
    • Camberwell, Victoria, Australia, 3124
      • Emeritus Research
    • Carlton, Victoria, Australia, 3053
      • Skin Health Institute Inc.
    • East Melbourne, Victoria, Australia, 3002
      • Sinclair Dermatology
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
      • Fremantle Dermatology
    • Victoria Park, Western Australia, Australia, 06100
      • Burswood Dermatology
• Canada
  • Alberta
    • Red Deer, Alberta, Canada, T4P1K4
      • CARe Clinic
  • Ontario
    • Ajax, Ontario, Canada, L1S7K8
      • CCA Medical Research
    • Cobourg, Ontario, Canada, K9A 0Z4
      • Skin Health
    • Ottawa, Ontario, Canada, K2G6E2
      • Dermatology and Dermatologic Surgery
    • Richmond Hill, Ontario, Canada, L4B 1A5
      • The Centre for Dermatology
• Estonia
  • Tartu, Estonia, 50160
    • Kliiniliste Uuringute Keskus OU
• France
  • Bordeaux Cedex, France, 33075
    • CHU de Bordeaux Hôpital Saint André
  • Dijon Cedex, France, 21079
    • CHU DIJON - Hopital le Bocage
  • Martigues, France, 13500
    • Cabinet Medical
  • Toulouse cedex 9, France, 31059
    • Hôpital Larrey
  • Cedex 10
    • Paris, Cedex 10, France, 75475
      • Hôpital Saint-Louis
• Korea, Republic of
  • Incheon, Korea, Republic of, 21431
    • Incheon St. Mary's Hospital
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 07441
    • Hallym University Kangnam Sacred Heart Hospital
  • Seoul, Korea, Republic of, 06973
    • Chungang University Hospital
  • Gyeonggi-do
    • Ansan-si, Gyeonggi-do, Korea, Republic of, 15355
      • Korea University Ansan Hospital
  • Korea
    • Pusan, Korea, Korea, Republic of, 49241
      • Pusan National University Hospital
    • Seoul, Korea, Korea, Republic of, 04763
      • Hanyang University Medical Center
    • Ulsan, Korea, Korea, Republic of, 44033
      • Ulsan University Hospital
  • Kyung Gi-Do, Korea
    • Suwon-si, Kyung Gi-Do, Korea, Korea, Republic of, 16499
      • Ajou University Hospital
  • Yongsan-gu
    • Seoul, Yongsan-gu, Korea, Republic of, 04401
      • Soon Chun Hyang University Seoul Hospital
• Latvia
  • Riga, Latvia, LV-1001
    • Clinic of Dermatology and STD
  • Riga, Latvia, LV-1009
    • Health and Aesthetics Ltd
  • Riga, Latvia, LV-1011
    • Latvian Dermatology Institute
  • Riga, Latvia, LV-1003
    • Health Center 4, Affiliate Diagnostic Center
  • Talsi, Latvia, LV-3201
    • Smite Aija - Practice in Dermatology Venereology
• Lithuania
  • Kaunas, Lithuania, LT-44192
    • JSC "CD8 Alergology Clinic"
  • Kaunas, Lithuania, LT-50161
    • Hospital of Lithuanian University of Health Sciences Kauno klinikos
  • Vilnius, Lithuania, LT-07195
    • Jsc Renmeda
  • Vilnius, Lithuania, LT-08109
    • JSC "Center for Diagnosis and Treatment of Allergic Diseases"
  • Vilnius, Lithuania, LT-08406
    • Children's Hospital, Affiliate of Vilnius University Hospital Santaros Klinikos
  • Vilnius, Lithuania, LT-08441
    • Vilnius University Hospital Santaros Klinikos
  • Vilnius, Lithuania, LT-08406
    • Inlita (Santaros CTC)
• Poland
  • Katowice, Poland, 40-851
    • GynCentrum Sp z o.o.
  • Krakow, Poland, 31-023
    • Specjalistyczny Osrodek Alergologiczno-Internistyczny ALL-ME
  • Lublin, Poland, 20-081
    • Samodzielny Publiczny Szpital Kliniczny nr 1
  • Poznan, Poland, 60-214
    • Centrum Alergologii Teresa Hofman
  • Warszawa, Poland, 01-142
    • Clinical Research Group Sp. z o.o.
  • Wroclaw, Poland, 50-566
    • CityClinic Przychodnia Lekarsko-Psychologiczna
  • Malopolska
    • Tarnow, Malopolska, Poland, 33100
      • Alergo-Med Specjalistyczna Przychodnia Lekarska Sp Z O.O.
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-559
      • Diamond Clinic
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-507
      • Centralny Szpital Kliniczny Mswia
  • Slaskie
    • Katowice, Slaskie, Poland, 40-611
      • Centrum Medyczne Angelius Provita
  • West Pomeranian
    • Szczecin, West Pomeranian, Poland, 71-434
      • Twoja Przychodnia - Szczecinskie Centrum Medyczne
  • Wojewodztwo Podkarpackie
    • Iwonicz Zdroj, Wojewodztwo Podkarpackie, Poland, 38-440
      • Zespol Naukowo - Leczniczy "Iwolang" Sp. z o.o.
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario Alicante
  • Badalona, Spain, 08916
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Madrid, Spain, 28031
    • Hospital Infanta Leonor
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Barcelona
    • SANT BOI DE Llobrega, Barcelona, Spain, 08830
      • Sant Joan de Deu Serveis En Salut Mental
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Hospital de Basurto
• United States
  • Arkansas
    • Fort Smith, Arkansas, United States, 72916
      • Johnson Dermatology
  • California
    • Beverly Hills, California, United States, 90211
      • Wallace Medical Group, Inc.
    • Encinitas, California, United States, 92024
      • California Dermatology & Clinical Research Institute
    • Fountain Valley, California, United States, 92708
      • Belle Aimee Skincare Clinic
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
    • San Diego, California, United States, 92119
      • ACRC Studies
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
      • Central Connecticut Dermatology
  • Florida
    • Clearwater, Florida, United States, 33765
      • St. Francis Medical Institute
    • Miami, Florida, United States, 33145
      • Community Research Foundation Inc
    • Tampa, Florida, United States, 33613-1244
      • Forcare Clinical Research
  • Georgia
    • Columbus, Georgia, United States, 31903
      • IACT Health - VHC
  • Indiana
    • Plainfield, Indiana, United States, 46168
      • The Indiana Clinical Trials Center
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Skin Sciences, PLLC
  • Massachusetts
    • Quincy, Massachusetts, United States, 02169
      • Beacon Clinical Research, LLC
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Saint Joseph, Michigan, United States, 49085
      • St Joseph Dermatology and Vein Clinic
  • Missouri
    • Saint Joseph, Missouri, United States, 64506
      • MediSearch Clinical Trials
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • JDR Dermatology Research
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • Allcutis Research
  • New York
    • New York, New York, United States, 10075
      • Sadick Research Group
    • New York, New York, United States, 10029
      • Icahn Sch of Med at Mt. Sinai
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
    • Tulsa, Oklahoma, United States, 74136
      • Vital Prospects Clinical Research Institute, P.C.
  • Oregon
    • Medford, Oregon, United States, 97504
      • Clinical Research Institute
    • Portland, Oregon, United States, 97223
      • Oregon Medical Research Center
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Clinical Partners, LLC
  • Texas
    • Bellaire, Texas, United States, 77401
      • Bellaire Dermatology
    • San Antonio, Texas, United States, 78213
      • Progressive Clinical Research
  • Washington
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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 250 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 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.	Other: Placebo; Subcutaneous Injection; Biological: Lebrikizumab; Subcutaneous injection; Other Names: LY3650150; DRM06
Experimental: Lebrikizumab 250 Q4W; Maintenance 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	Other: Placebo; Subcutaneous Injection; Biological: Lebrikizumab; Subcutaneous injection; Other Names: LY3650150; DRM06
Experimental: Escape Arm (Lebrikizumab Q2W); Maintenance 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.	Other: Placebo; Subcutaneous Injection; 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 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 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 an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 in Adults	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 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 score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe). The EASI-90 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the EASI score.	Baseline to Week 16
Percent 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 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
Percent Change in EASI Score From Baseline to Week 16	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease, 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 score was obtained by weight-averaging these 4 scores and will range from 0 (none) 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
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
Percentage of Participants Achieving EASI-90 From Baseline to Week 4	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 score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe). The EASI-90 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the EASI score.	Baseline to Week 4
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 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 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
Percent 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
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 Sleep-loss Score ≥2 Points at Baseline Who Achieve a ≥2 Points Reduction From Baseline 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.	Baseline to 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
Percent Change in SCORing Atopic Dermatitis (SCORAD) From Baseline to Week 16	The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. LS Mean was calculated using the 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): Average Serum Concentration of Lebrikizumab at Week 52	PK: Average serum concentration of lebrikizumab at the Week 52 trough timepoint. Serum concentration is a combined measure obtained from Baseline, Week 4, Week 16, Week 32, Week 52 and average measure was reported at week 52.	Predose: Baseline, Week 4, Week 16, Week 32, Week 52
Percentage of Participants From Those Re-randomized Having Achieved EASI-75 at Week 16 Who Continued 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 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 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 and 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 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
Percent Change in SCORAD (Having Achieved EASI-75 at Week 16) From Baseline at Week 52	The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. LS mean was calculated using ANCOVA model with treatment group, baseline value, and stratification factors 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 EQ-5D-5L is a 2-part measurement. The first part is 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, with higher score indicating 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
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
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 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 depression has 8 questions on Emotion Distress-Depression (or Pediatric Depressive 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 depression. 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. The PROMIS measures will be completed by the participant in the study clinic. 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. The PROMIS measures will be completed by the participant in the study clinic. PROMIS depression has 8 questions on Emotion Distress-Depression (or Pediatric Depressive 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 depression. 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 - Adolescents	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

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Evaluation of the Efficacy and Safety of Lebrikizumab (LY3650150) in Moderate to Severe Atopic Dermatitis (ADvocate1)

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2019
• Primary Completion (Actual): June 21, 2021
• Study Completion (Actual): May 3, 2022

Study Registration Dates

• First Submitted: October 29, 2019
• First Submitted That Met QC Criteria: October 30, 2019
• First Posted (Actual): October 31, 2019

Study Record Updates

• Last Update Posted (Actual): November 30, 2022
• Last Update Submitted That Met QC Criteria: November 2, 2022
• Last Verified: November 1, 2022

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: 17801; 2019-002932-10 (EudraCT Number); J2T-DM-KGAB (Other Identifier: Eli Lilly and Company); DRM06-AD04 (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; Statistical Analysis Plan (SAP); Clinical Study Report (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