A Study of LY3454738 in the Treatment of Adult Participants With Moderate-to-Severe Atopic Dermatitis

A Phase 2, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, 52 Week Study to Evaluate the Efficacy and Safety of LY3454738 in the Treatment of Adult Patients With Moderate-to-Severe Atopic Dermatitis

The main purpose of this study is to describe the efficacy and safety of LY3454738 in adult participants with moderate-to-severe atopic dermatitis (AD).

Study Overview

• Status: Terminated
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Placebo; Drug: LY3454738

• Study Type: Interventional
• Enrollment (Actual): 234
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G2J 0C4
    • ALPHA Recherche Clinique
  • Alberta
    • Calgary, Alberta, Canada, T2W 4X9
      • Rejuvenation Dermatology
    • Edmonton, Alberta, Canada, T5J 3S9
      • Rejuvenation Dermatology
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3M 3Z4
      • Wiseman Dermatology Research Inc.
  • Ontario
    • Ajax, Ontario, Canada, L1S 7K8
      • CCA Medical Research
    • Hamilton, Ontario, Canada, L8S 1G5
      • Hamilton Allergy
    • Markham, Ontario, Canada, L3P 1X3
      • Lynderm Research Inc.
    • Toronto, Ontario, Canada, M4E 1R7
      • FACET Dermatology
• China
  • Wuhan, China, 430060
    • Renmin Hospital of Wuhan University
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University
  • Jiangsu
    • Zhenjiang, Jiangsu, China, 212000
      • Affiliated Hospital of Jiangsu University
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200040
      • Huashan Hospital, Fudan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310014
      • Zhejiang Provincial People's Hospital
• Hungary
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
  • Jász-Nagykun-Szolnok
    • Szolnok, Jász-Nagykun-Szolnok, Hungary, 5000
      • Allergo-Derm Bakos Kft
  • Somogy County
    • Kaposvár, Somogy County, Hungary, 7400
      • Somogy Megyei Kaposi Mor Oktato Korhaz
  • Vas County
    • Szombathely, Vas County, Hungary, 9700
      • Markusovszky Egyetemi Oktatokorhaz
  • Veszprém City
    • Veszprém, Veszprém City, Hungary, 8200
      • Medmare Bt
• Japan
  • Fukuoka
    • Chikushino-shi, Fukuoka, Japan, 818-0083
      • Yasumoto Dermatology Clinic
  • Hokkaido
    • Obihiro-shi, Hokkaido, Japan, 080-0013
      • Takagi Dermatological Clinic
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 221-0825
      • Nomura Dermatology Clinic
  • Osaka
    • Sakai, Osaka, Japan, 593-8324
      • Dermatology and Ophthalmology Kume Clinic
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 103-0025
      • Nihonbashi Sakura Clinic
    • Tachikawa, Tokyo, Japan, 190-0023
      • Tachikawa Dermatology Clinic
• Mexico
  • Chihuahua City, Mexico, 31207
    • Scientia Investigacion Clinica S.C.
  • Oaxaca City, Mexico, 68020
    • Centro de Investigacion Clinica de Oaxaca
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44630
      • Centro de Atención en Enfermedades Inflamatorias CATEI
  • Mexico City
    • Cuauhtémoc, Ciudad de México, Mexico City, Mexico, 06100
      • Cryptex Investigación Clínica S.A. de C.V.
    • Mexico City, Mexico City, Mexico, 06700
      • Trials in Medicine
    • Mexico City, Mexico City, Mexico, 03100
      • RM Pharma Specialists
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64718
      • Eukarya PharmaSite
• Poland
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-559
      • Diamond Clinic
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 00-874
      • MICS Centrum Medyczne Warszawa
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-375
      • Specderm Poznanska
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-546
      • Centrum Badan Klinicznych PI-House sp. z o.o.
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 90-265
      • "DERMED" Centrum Medyczne Sp. z o.o.
    • Lodz, Łódź Voivodeship, Poland, 90-436
      • Dermoklinika - Centrum Medyczne spółka cywilna M. Kierstan, J. Narbutt, A. Lesiak
• South Korea
  • Incheon-gwangyeoksi [Incheon]
    • Bupyeong-gu, Incheon-gwangyeoksi [Incheon], South Korea, 21431
      • The Catholic University of Korea, Incheon St. Mary's Hospital
  • Kyǒnggi-do
    • Ansan-si, Kyǒnggi-do, South Korea, 15355
      • Korea University Ansan Hospital
  • Pusan-Kwangyǒkshi
    • Busan, Pusan-Kwangyǒkshi, South Korea, 49241
      • Pusan National University Hospital
  • Seoul-teukbyeolsi [Seoul]
    • Dongjak-gu, Seoul-teukbyeolsi [Seoul], South Korea, 06973
      • Chung-Ang University Hospital
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 01812
      • National medical center
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 07441
      • Hallym University Kangnam Sacred Heart Hospital
• Taiwan
  • Hsinchu, Taiwan, 300
    • National Taiwan University Hospital - Hsinchu branch
  • New Taipei City, Taiwan, 235
    • Taipei Medical University Shuang Ho Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan District, Taiwan, 333
    • Chang Gung Medical Foundation-Linkou Branch
  • Kaohsiung
    • Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan, 83301
      • Chang Gung Memorial Hospital at Kaohsiung
  • New Taipei
    • New Taipei City, New Taipei, Taiwan, 236
      • New Taipei Municipal TuCheng Hospital
  • Taichung
    • Taichung, Taichung, Taiwan, 402
      • Chung Shan Medical University Hospital
  • Taipei
    • Taipei City, Taipei, Taiwan, 114
      • Tri-Service General Hospital
• United States
  • Arkansas
    • Fort Smith, Arkansas, United States, 72916
      • Johnson Dermatology
    • North Little Rock, Arkansas, United States, 72217
      • Arkansas Research Trials
  • California
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
  • Florida
    • Hollywood, Florida, United States, 33024
      • Encore Medical Research
    • Winter Park, Florida, United States, 32789
      • Conquest Research
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Allergy and Asthma Specialist
  • Michigan
    • Troy, Michigan, United States, 48084
      • Revival Research Institute, LLC
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • ActivMed Practices & Research, Inc.
  • New Jersey
    • Kenilworth, New Jersey, United States, 07033
      • Metropolitan Dermatology - Clark
  • Oregon
    • Portland, Oregon, United States, 97210
      • Oregon Dermatology and Research Center
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • DermDox Centers for Dermatology
  • Texas
    • San Antonio, Texas, United States, 78213
      • Progressive Clinical Research
    • Webster, Texas, United States, 77598
      • Center for Clinical Studies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Are candidates for systemic therapy.

ISA specific:

• Have moderate-to-severe AD, defined as meeting all of the following criteria, at the first dosing visit:

  • EASI score greater than or equal to (≥)16
  • vIGA-AD score ≥3, and
  • ≥10% of BSA involvement (per EASI BSA).
• Have applied at least 1 emollient every day for at least 2 weeks before the day of the first dose of study intervention in this ISA and agree to daily use of at least 1 emollient continuously throughout the study.

Exclusion Criteria:

ISA specific:

• Have, in the screening period, any of the skin conditions, infections, or medical conditions listed under master IMMB.
• Are currently being treated with topical or systemic therapy
• Recent treatment with experimental (biologics and/or small molecules) - doesn't apply for subset of participants who must have been exposed to biologics and/or small molecules.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo administered subcutaneously (SC) every two weeks (Q2W) from baseline to Week 14. Week 16 responders entered maintenance period and received placebo SC every four weeks (Q4W) until Week 40. Week 16 non-responders entered escape arm and received 800 milligrams (mg) of LY3454738 administered SC Q4W until Week 40.	Drug: Placebo; Administered SC; Drug: LY3454738; Administered SC
Experimental: 75 mg LY3454738; Participants received 75 mg of LY3454738 administered SC Q2W from baseline until Week 14. Week 16 responders entered maintenance period and received 150 mg of LY3454738 administered SC Q4W until Week 40. Week 16 non-responders entered escape arm and received 800 mg of LY3454738 administered SC Q4W until Week 40.	Drug: LY3454738; Administered SC
Experimental: 300 mg LY3454738; Participants received 300 mg of LY3454738 administered SC Q2W from baseline until Week 14. Week 16 responders entered maintenance period and continued receiving 300 mg of LY3454738 administered SC Q4W until Week 40. Week 16 non-responders entered escape arm and received 800 mg of LY3454738 administered SC Q4W until Week 40.	Drug: LY3454738; Administered SC
Experimental: 800 mg LY3454738; Participants received 800 mg of LY3454738 administered SC Q2W from baseline until Week 14. Week 16 responders entered maintenance period and were re-randomized to either receive 800 mg of LY3454738 or placebo administered SC Q4W until Week 40. Week 16 non-responders entered escape arm and received 800 mg of LY3454738 administered SC Q4W until Week 40.	Drug: LY3454738; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Biologic and Small Molecule Naive Participants Achieving Eczema Area and Severity Index (EASI) 75 (≥75% Reduction in EASI Score) at 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.	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Biologic and Small Molecule Naive Participants Achieving EASI-50 (≥ 50% Reduction in EASI Score) at 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-50 responder is defined as a participant who achieves a ≥ 50% reduction from baseline in the EASI score.	Week 16
Percentage of Biologic and Small Molecule Naive Participants Achieving EASI-90 (≥ 90% Reduction in EASI Score) at 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.	Week 16
Percentage of Biologic and Small Molecule Naive Participants Achieving SCORing Atopic Dermatitis (SCORAD) 75 at 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 a visual analogue scales (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. The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score.	Week 16
Percentage of Biologic and Small Molecule Naive Participants Achieving SCORAD-90 at 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 a visual analogue scales (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. The SCORAD90 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the SCORAD score.	Week 16
Percentage of Biologic and Small Molecule Naive Participants Achieving Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 at Week 16	vIGA-AD is a standardized clinical tool used to measure the severity of AD. It is a static 5-point scale ranging from 0 to 4, used to grade overall disease severity. Higher viGA-AD scores represent more severe disease. The scale is as below: 0-Clear: No inflammatory signs of atopic dermatitis (erythema, induration/papulation, lichenification, oozing/crusting). Post-inflammatory hyperpigmentation and/or hypopigmentation may be present.; 1-Almost Clear: Barely perceptible erythema, induration/papulation, and/or lichenification. No oozing/crusting.; 2-Mild: Slight but definite erythema (pink), induration/papulation, and/or lichenification. No oozing/crusting.; 3-Moderate: Clearly perceptible erythema (dull red), induration/papulation, and/or lichenification. Oozing and crusting may be present.; 4-Severe: Marked erythema (deep or bright red), induration/papulation, and/or lichenification. Disease is widespread in extent. Oozing or crusting may be present.	Week 16
Percentage of Biologic and Small Molecule Naive Participants Achieving ≥4-point Improvement From Baseline in Itch Numeric Rating Scale (NRS) in the Subset of Biologic and Small Molecule Naive Participants With ≥4-point Itch NRS at Baseline	Percentage of biologic and small molecule naive participants achieving ≥4-point improvement from baseline in Itch NRS in the Subset of biologic and small molecule naive participants with ≥4-point Itch NRS at Baseline were reported. The Itch NRS is a 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, Week 16
Mean Percent Change From Baseline in EASI in Biologic and Small Molecule Naive Participants	Mean percent change from baseline in EASI in biologic and small molecule naive participants was reported.	Baseline, Week 16
Mean Percent Change From Baseline in SCORAD in Biologic and Small Molecule Naive Participants	Mean percent change from baseline in SCORAD in biologic and small molecule naive participants was reported.	Baseline, Week 16
Percentage of Biologic and Small Molecule Experienced Participants Achieving EASI-75 at 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.	Week 16
Pharmacokinetics (PK): Serum Trough Concentrations of LY3454738 at Week 16	PK: Serum trough concentrations of LY3454738 were reported.	Day 113 post Day 1 Dose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• 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

• A Study of LY3454738 in the Treatment of Adult Participants With Moderate-to-Severe Atopic Dermatitis

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2023
• Primary Completion (Actual): October 10, 2024
• Study Completion (Actual): March 14, 2025

Study Registration Dates

• First Submitted: June 12, 2023
• First Submitted That Met QC Criteria: June 12, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Genetic; Skin Diseases, Eczematous; Dermatitis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Dermatitis, Atopic
• Other Study ID Numbers: 18569; J4E-MC-FR01 (Other Identifier: Eli Lilly and Company); FR01 ISA (Other Identifier: Eli Lilly and Company); J4E-MC-IMMB Master Protocol (Other Identifier: Eli Lilly and Company); 2022-502888-38-00 (Other Identifier: EU Trial Number)

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 European Union (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