A Study of Lebrikizumab (LY3650150) in Combination With Topical Corticosteroids in Japanese Participants With Moderate-to-Severe Atopic Dermatitis (ADhere-J)

A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Lebrikizumab When Used in Combination With Topical Corticosteroid Treatment in Japanese Patients With Moderate-to-Severe Atopic Dermatitis

The main purpose of this study is to evaluate the efficacy and safety of lebrikizumab in combination with a topical corticosteroids in Japanese participants with atopic dermatitis.

Study Overview

• Status: Completed
• Conditions: Skin Diseases; Skin Diseases, Genetic; Dermatitis; Eczema; Dermatitis, Atopic
• Intervention / Treatment: Drug: Placebo; Drug: Lebrikizumab; Drug: Topical Corticosteroid

• Study Type: Interventional
• Enrollment (Actual): 286
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 819-0167
    • Matsuda Tomoko Dermatological Clinic
  • Kyoto-shi, Japan, 602 8566
    • Kyoto Furitsu Medical University Hospital
  • Osaka, Japan, 545-8586
    • Osaka City University Hospital
  • Osaka, Japan, 554-0021
    • Goto Dermatology Clinic
  • Chiba
    • Ainokawa, Ichikawa-shi, Chiba, Japan, 272-0143
      • Yanagihara dermatology clinic
    • Ichikawa-shi, Chiba, Japan, 272-0033
      • Kawashima Dermatology Clinic
    • Matsudo, Chiba, Japan, 270-2223
      • Charme Clinique
  • Fukuoka
    • Chikushino-city, Fukuoka, Japan, 818-0083
      • Yasumoto Dermatology Clinic
    • Fukutsu, Fukuoka, Japan, 811-3217
      • Hino Dermatology Clinic
  • Hiroshima-ken
    • Hiroshima-shi, Hiroshima-ken, Japan, 734-8551
      • Hiroshima University Hospital
  • Hokkaido
    • Obihiro, Hokkaido, Japan, 080-0013
      • Takagi Dermatology
    • Sapporo, Hokkaido, Japan, 060-0063
      • Sapporo Skin Clinic
    • Sapporo-shi, Hokkaido, Japan, 060-0807
      • Kobayashi Skin Clinic
  • Hyogo
    • Kobe, Hyogo, Japan, 657-0846
      • Dermatology Shimizu Clinic
  • Ibaraki
    • Inashiki-gun, Ibaraki, Japan, 300-0395
      • Ibaraki Medical Center
  • Ishikawa
    • Nonoichi-shi, Ishikawa, Japan, 921-8801
      • Kaji Dermatology Clinic
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 211-0063
      • Kosugi Dermatology Clinic
    • Nishi-ku, Yokohama-city, Kanagawa, Japan, 220-6208
      • Queen's Square Dermatology and Allergology
    • Yokohama-shi, Kanagawa, Japan, 221-0825
      • Nomura Dermatology Clinic
  • Kumamoto
    • Kashima-machi, Kamimashiki-gun, Kumamoto, Japan, 861-3101
      • Noguchi Dermatology
    • Kumamoto Shi, Kumamoto, Japan, 860-0066
      • Jyouzanhihuka・Hinyoukika Clinic
  • Osaka
    • Habikino, Osaka, Japan, 583-8588
      • Osaka Habikino Medical Center
    • Izumiotsu-shi, Osaka, Japan, 595-0025
      • Mochida Dermatology Clinic
    • Sakai City, Osaka, Japan, 593-8324
      • Kume Clinic
    • Takatsuki, Osaka, Japan, 569-0824
      • Yoshikawa Dermatology Clinic
  • Saitama
    • Ohmiya-ku,Saitama-shi, Saitama, Japan, 330-0854
      • Sanrui Dermatology Clinic
  • Tochigi
    • Shimotsuga-Gun, Tochigi, Japan, 321 0293
      • Dokkyo Medical University Hospital
  • Tokyo
    • Chiyoda-ku, Tokyo, Japan, 101-0021
      • Akihabara Skin Clinic
    • Edogawa-ku, Tokyo, Japan, 133-0057
      • Sumire Dermatology Clinic
    • Koto-ku, Tokyo, Japan, 136-0074
      • Maruyama Dermatology Clinic
    • Machida-shi, Tokyo, Japan, 194-0013
      • Hamaguchi Skin Clinic
    • Minato-Ku, Tokyo, Japan, 108-0014
      • Mita Dermatology Clinic
    • Ota-ku, Tokyo, Japan, 143-0023
      • Tanpopo Dermatology Clinic
    • Shinjuku, Tokyo, Japan, 169-0075
      • Yamate Dermatological Clinic
    • Sumida-ku, Tokyo, Japan, 130-0014
      • Yoshihara Dermatology Clinic
    • Tachikawa-shi, Tokyo, Japan, 190-0023
      • Tachikawa Dermatology Clinic
  • Toyama
    • Takaoka-shi, Toyama, Japan, 9330871
      • Shirasaki Clinic

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Have chronic Atopic Dermatitis (AD) that has been present for ≥1 year before the screening.

• Have moderate-to-severe AD, including all of the following:

  • EASI score ≥16 at the baseline
  • IGA score ≥3 (scale of 0 to 4) at the baseline
  • AD involvement on ≥10% of Body Surface Area (BSA) at the baseline

• Have a documented history provided by a physician and/or investigator of inadequate response to existing topical medications within 6 months preceding screening as defined by at least 1 of the following:

  • Inability to achieve good disease control, defined as mild disease or better (for example, IGA ≤2) after use of at least a medium-potency topical corticosteroids (TCS) for at least 4 weeks, or for the maximum duration recommended by the product prescribing information (for example, 14 days for super-potent TCS), whichever is shorter. Topical corticosteroids may be used with or without Topical calcineurin inhibitors (TCI) and/or topical Janus Kinase (JAK) inhibitors.
  • Participants who failed systemic therapies intended to treat AD within 6 months preceding screening, such as cyclosporine, methotrexate (MTX), azathioprine, and mycophenolate mofetil (MMF), will also be considered as surrogates for having inadequate response to topical therapy.
• Body weight ≥40 kilogram (kg)

Exclusion Criteria:

• Have a history of anaphylaxis
• Have uncontrolled chronic disease that might require bursts of oral corticosteroids for example, comorbid severe uncontrolled asthma within the past 12 months requiring systemic corticosteroid treatment or hospitalization for >24 hours at baseline.
• Have an active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline or superficial skin infections within 1 week before the baseline.
• Evidence of acute or chronic hepatitis or known liver cirrhosis.
• Have a history of pneumocystis pneumonia (PCP) or a positive beta-D-glucan test at screening and a confirmed diagnosis of PCP.
• Have a history of human immunodeficiency virus (HIV) infection or positive HIV serology at screening.
• Have presence of skin comorbidities (for example, sclerosis, psoriasis, or lupus erythematosus) that may interfere with study assessments.
• Have presence of significant uncontrolled neuropsychiatric disorder.
• Have been exposed to a live vaccine within 12 weeks prior to baseline or are expected to need/receive a live vaccine during the study or up to 125 days after the last dose of study drug.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lebrikizumab 250 mg Every 4 weeks (Q4W); Participants received 500 mg of Lebrikizumab (2 x 250 mg) subcutaneous (SC) injections as a loading dose at Baseline followed by 250 mg of Lebrikizumab administered SC Q4W from Week 4 until Week 12, in combination with topical corticosteroid. Week 16 responders entered maintenance period and continued with the same treatment. Week 16 non responders entered Escape Arm and received Lebrikizumab 250 mg Q2W until Week 68.	Drug: Lebrikizumab; Administered SC; Other Names: LY3650150; Drug: Topical Corticosteroid; Self-applied
Experimental: Lebrikizumab 250 mg Every 2 weeks (Q2W); Participants received 500 mg of Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by 250 mg of Lebrikizumab administered SC Q2W from Week 4 until Week 14, in combination with topical corticosteroid. Week 16 responders entered maintenance period and were randomly allocated to receive 250 mg lebrikizumab Q2W or 250 mg lebrikizumab Q4W, in a 1:1 ratio. Week 16 non responders entered Escape Arm and received Lebrikizumab 250 mg Q2W until Week 68.	Drug: Lebrikizumab; Administered SC; Other Names: LY3650150; Drug: Topical Corticosteroid; Self-applied
Placebo Comparator: Placebo; Participants received two SC injections of Placebo as a loading dose at Baseline in combination with topical corticosteroid and Week 2 followed by a single injection Q2W from Week 4 until Week 14. Week 16 responders entered maintenance period and continued with the same treatment. Week 16 non responders entered Escape Arm and received Lebrikizumab 250 mg Q2W until Week 68.	Drug: Placebo; Administered SC; Drug: Topical Corticosteroid; Self-applied

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an Investigators 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 Severity Index-75 (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
Percent Change in Eczema Area Severity Index (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). Least Square (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 to Week 16
Percentage of Participants Achieving EASI-90 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 Participants With an Itch Numeric Rating Scale (NRS) Score of ≥4-points at Baseline Who Achieve A ≥4-point Reduction From Baseline to Week 1	The Itch Numeric Rating Scale (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 to Week 1
Percentage of Participants With an Itch NRS Score of ≥4-points at Baseline Who Achieve A ≥4-point Reduction From Baseline to Week 2	The Itch Numeric Rating Scale (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 to Week 2
Percentage of Participants With an Itch NRS Score of ≥4-points at Baseline Who Achieve A ≥4-point Reduction From Baseline to Week 4	The Itch Numeric Rating Scale (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 to Week 4
Percentage of Participants With an Itch NRS Score of ≥4-points at Baseline Who Achieve A ≥4-point Reduction From Baseline to Week 16	The Itch Numeric Rating Scale (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 to Week 16

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 Lebrikizumab (LY3650150) in Combination With Topical Corticosteroids in Japanese Participants With Moderate-to-Severe Atopic Dermatitis (ADhere-J)

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2021
• Primary Completion (Actual): July 31, 2022
• Study Completion (Actual): February 1, 2023

Study Registration Dates

• First Submitted: February 10, 2021
• First Submitted That Met QC Criteria: February 17, 2021
• First Posted (Actual): February 18, 2021

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Corticosteroids
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Skin Diseases; Dermatitis, Atopic; Genetic Diseases, Inborn; Skin Diseases, Genetic
• Other Study ID Numbers: 17953; J2T-JE-KGAL (Other Identifier: Eli Lilly and Company)

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
• product manufactured in and exported from the U.S.: Yes