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

NCT ID: NCT04146363

Last Updated: 2022-11-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 424 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-24
• Study Completion Date: 2022-05-03

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.

Conditions

Atopic Dermatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Subcutaneous Injection

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.

Group Type: EXPERIMENTAL

Lebrikizumab

Intervention Type: BIOLOGICAL

Subcutaneous injection

Placebo

Intervention Type: OTHER

Subcutaneous Injection

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

Group Type: EXPERIMENTAL

Lebrikizumab

Intervention Type: BIOLOGICAL

Subcutaneous injection

Placebo

Intervention Type: OTHER

Subcutaneous Injection

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.

Group Type: EXPERIMENTAL

Lebrikizumab

Intervention Type: BIOLOGICAL

Subcutaneous injection

Placebo

Intervention Type: OTHER

Subcutaneous Injection

Interventions

Lebrikizumab

Subcutaneous injection

Intervention Type: BIOLOGICAL

Placebo

Subcutaneous Injection

Intervention Type: OTHER

Other Intervention Names

LY3650150; DRM06

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dermira, Inc.

INDUSTRY

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

Johnson Dermatology

Fort Smith, Arkansas, United States

Wallace Medical Group, Inc.

Beverly Hills, California, United States

California Dermatology & Clinical Research Institute

Encinitas, California, United States

Belle Aimee Skincare Clinic

Fountain Valley, California, United States

Dermatology Research Associates

Los Angeles, California, United States

ACRC Studies

San Diego, California, United States

Central Connecticut Dermatology

Cromwell, Connecticut, United States

St. Francis Medical Institute

Clearwater, Florida, United States

Community Research Foundation Inc

Miami, Florida, United States

ForCare Clinical Research

Tampa, Florida, United States

IACT Health - VHC

Columbus, Georgia, United States

The Indiana Clinical Trials Center

Plainfield, Indiana, United States

Skin Sciences, PLLC

Louisville, Kentucky, United States

Beacon Clinical Research, LLC

Quincy, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

St Joseph Dermatology and Vein Clinic

Saint Joseph, Michigan, United States

MediSearch Clinical Trials

Saint Joseph, Missouri, United States

JDR Dermatology Research

Las Vegas, Nevada, United States

ALLCUTIS Research

Portsmouth, New Hampshire, United States

Icahn Sch of Med at Mt. Sinai

New York, New York, United States

Sadick Research Group

New York, New York, United States

Wake Research Associates

Raleigh, North Carolina, United States

Lynn Health Science Institute

Oklahoma City, Oklahoma, United States

Vital Prospects Clinical Research Institute, P.C.

Tulsa, Oklahoma, United States

Clinical Research Institute

Medford, Oregon, United States

Oregon Medical Research Center

Portland, Oregon, United States

Clinical Partners, LLC

Johnston, Rhode Island, United States

Bellaire Dermatology

Bellaire, Texas, United States

Progressive Clinical Research

San Antonio, Texas, United States

Premier Clinical Research

Spokane, Washington, United States

The St. George Hospital

Kogarah, New South Wales, Australia

Holdsworth House Medical Practice

Sydney, New South Wales, Australia

Skin & Cancer Foundation Australia

Westmead, New South Wales, Australia

The Skin Centre

Benowa, Queensland, Australia

Veracity Clinical Research Pty Ltd

Woolloongabba, Queensland, Australia

Eastern Clinical Research Unit

Box Hill, Victoria, Australia

Emeritus Research

Camberwell, Victoria, Australia

Skin Health Institute Inc.

Carlton, Victoria, Australia

Sinclair Dermatology

East Melbourne, Victoria, Australia

Fremantle Dermatology

Fremantle, Western Australia, Australia

Burswood Dermatology

Victoria Park, Western Australia, Australia

CARe Clinic

Red Deer, Alberta, Canada

CCA Medical Research

Ajax, Ontario, Canada

Skin Health

Cobourg, Ontario, Canada

Dermatology and Dermatologic Surgery

Ottawa, Ontario, Canada

The Centre for Dermatology

Richmond Hill, Ontario, Canada

Kliiniliste uuringute Keskus OU

Tartu, , Estonia

Hopital Saint-Louis

Paris, Cedex 10, France

CHU de Bordeaux Hopital Saint Andre

Bordeaux, , France

CHU DIJON - Hopital le Bocage

Dijon, , France

Cabinet Médical

Martigues, , France

Hopital Larrey

Toulouse, , France

Clinic of Dermatology and STD

Riga, , Latvia

Health Center 4, Affiliate Diagnostic Center

Riga, , Latvia

Health and Aesthetics LTD

Riga, , Latvia

Latvian Dermatology Institute

Riga, , Latvia

Smite Aija - Practice in Dermatology Venereology

Talsi, , Latvia

JSC "CD8 Alergology Clinic"

Kaunas, , Lithuania

Hospital of Lithuanian University of Health Sciences Kauno klinikos

Kaunas, , Lithuania

Jsc Renmeda

Vilnius, , Lithuania

JSC "Center for Diagnosis and Treatment of Allergic Diseases"

Vilnius, , Lithuania

Children's Hospital, Affiliate of Vilnius University Hospital Santaros klinikos

Vilnius, , Lithuania

Inlita (Santaros CTC)

Vilnius, , Lithuania

Vilnius University Hospital Santaros klinikos

Vilnius, , Lithuania

Diamond Clinic

Krakow, Lesser Poland Voivodeship, Poland

Alergo-Med Specjalistyczna Przychodnia Lekarska Sp Z O.O.

Tarnów, Malopolska, Poland

Centralny Szpital Kliniczny MSWiA

Warsaw, Masovian Voivodeship, Poland

Zespol Naukowo - Leczniczy "Iwolang" Sp. z o.o.

Iwonicz-Zdrój, Podkarpackie Voivodeship, Poland

Centrum Medyczne Angelius Provita

Katowice, Silesian Voivodeship, Poland

Twoja Przychodnia - Szczecinskie Centrum Medyczne

Szczecin, West Pomeranian Voivodeship, Poland

GynCentrum Sp z o.o.

Katowice, , Poland

Specjalistyczny Osrodek Alergologiczno-Internistyczny ALL-ME

Krakow, , Poland

Samodzielny Publiczny Szpital Kliniczny nr 1

Lublin, , Poland

Centrum Alergologii Teresa Hofman

Poznan, , Poland

Clinical Research Group Sp. z o.o.

Warsaw, , Poland

CityClinic Przychodnia Lekarsko-Psychologiczna

Wroclaw, , Poland

Korea University Ansan Hospital

Ansan-si, Gyeonggi-do, South Korea

Pusan National University Hospital

Pusan, Korea, South Korea

Hanyang University Medical Center

Seoul, Korea, South Korea

Ulsan University Hospital

Ulsan, Korea, South Korea

Ajou University Hospital

Suwon, Kyung Gi-Do, Korea, South Korea

Soon Chun Hyang University Seoul Hospital

Seoul, Yongsan-gu, South Korea

Incheon St. Mary's Hospital

Incheon, , South Korea

Severance Hospital

Seoul, , South Korea

Konkuk University Medical Center

Seoul, , South Korea

Chungang University Hospital

Seoul, , South Korea

Hallym University Kangnam Sacred Heart Hospital

Seoul, , South Korea

Sant Joan de Deu Serveis En Salut Mental

SANT BOI de Llobrega, Barcelona, Spain

Hospital De Basurto

Bilbao, Vizcaya, Spain

Hospital General Universitario Alicante

Alicante, , Spain

Hospital Germans Trias i Pujol

Badalona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Infanta Leonor

Madrid, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Countries

United States; Australia; Canada; Estonia; France; Latvia; Lithuania; Poland; South Korea; Spain

References

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Reference Type: DERIVED

PMID: 40663228 (View on PubMed)

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Reference Type: DERIVED

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Lio 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.

Reference Type: DERIVED

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Simpson 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.

Reference Type: DERIVED

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Reference Type: DERIVED

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Blauvelt 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.

Reference Type: DERIVED

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://trials.lillytrialguide.com/en-US/trial/6duv4kD1B48RPwp63igF1U

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

Other Identifiers

2019-002932-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

J2T-DM-KGAB

Identifier Type: OTHER

Identifier Source: secondary_id

DRM06-AD04

Identifier Type: OTHER

Identifier Source: secondary_id

17801

Identifier Type: -

Identifier Source: org_study_id