A Study of Lebrikizumab in Participants With Persistent Moderate to Severe Atopic Dermatitis

A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Lebrikizumab in Patients With Persistent Moderate to Severe Atopic Dermatitis That is Inadequately Controlled by Topical Corticosteroids

This randomized, double-blind, placebo-controlled study will evaluate the safety and efficacy of lebrikizumab administered subcutaneously (SC) in adult participants with persistent moderate to severe atopic dermatitis (AD) who are inadequately controlled by topical corticosteroids (TCS). The study includes a screening visit, a 2-week run-in period, a 12-week blinded treatment period, and an 8-week safety follow-up period. Following screening visit, eligible participants will enter in run-in period (Days - 14 to - 1) during which a protocol-specified topical therapy regimen will be initiated. At the end of the run-in period, participants who have: 1) demonstrated compliance with the protocol-specified TCS regimen, and 2) who continue to fulfill the eligibility criteria will be randomized.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Lebrikizumab; Drug: Placebo; Drug: TCS Cream

• Study Type: Interventional
• Enrollment (Actual): 212
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • St George Dermatology and Skin Cancer Centre
  • Victoria
    • Carlton, Victoria, Australia, 3053
      • Skin & Cancer Foundation
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital; Dermatology Department
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
      • Fremantle Dermatology
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3A 2N1
      • Institute For Skin Advancement
  • British Columbia
    • Surrey, British Columbia, Canada, V3R 6A7
      • Guildford Dermatology Specialists
  • Ontario
    • Peterborough, Ontario, Canada, K9J 5K2
      • Dr. Melinda Gooderham Medicine Professional Corporation
    • Richmond Hill, Ontario, Canada, L4B 1A5
      • The Centre for Dermatology
    • Waterloo, Ontario, Canada, N2J 1C4
      • K. Papp Clinical Research Inc.
    • Windsor, Ontario, Canada, N8W 1E6
      • XLR8 Medical Research Inc.
  • Quebec
    • Montreal, Quebec, Canada, L2K 4L5
      • Innovaderm Research Inc.
• Czechia
  • Plzen, Czechia, 305 99
    • Faculty Hospital; Department of Dermatology
  • Prague 10, Czechia, 100 34
    • Charles University School of Medicine; Deptartment of Dermatology
  • Usti nad Labem, Czechia, 401 13
    • Masarykova nemocnice o.z; kozni oddeleni
• Finland
  • Helsinki, Finland, 00029
    • Helsinki University Central Hospital; Skin & Allergy Hospital
  • Tampere, Finland, 33520
    • Tampere University Hospital; Dermatology and allergology
  • Turku, Finland, 20250
    • Turku Central University Hospital; Dermatology and allergology
• France
  • Bordeaux, France, 33075
    • Hopital Saint Andre CHU De Bordeaux; Dermatologie
  • Dijon, France, 21079
    • Hopital du Bocage; Dermatologie
  • Nantes, France, 44093
    • Hopital Hotel Dieu Et Hme; Clinique Dermatologique
  • Nice cedex 3, France, 06200
    • Hopital l Archet 2; Ginestriere, Service de; Dermatologie
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon Sud; Dermatologie
• Germany
  • Berlin, Germany, 10117
    • Charite Mitte; Klinik fur Dermatologie
  • Bonn, Germany, 53127
    • Universitätsklinik Bonn
  • Frankfurt, Germany, 60590
    • Klinik Johann Wolfgang von Goethe Uni; Klinik für Dermatologie, Venerologie und Allergologie
  • Gera, Germany, 07548
    • SRH Wald-Klinikum Gera GmbH; Hautkrankheiten und Allergologie
  • Kiel, Germany, 24105
    • UKSH Kiel; Klinik für Dermatologie, Venerologie und Allergologie
  • Mainz, Germany, 55131
    • Universitätsklinikum Mainz
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 06973
    • Chungang University Hospital
• Netherlands
  • Amsterdam, Netherlands, 1100 DD
    • Academisch Medisch Centrum Universiteit Amsterdam; Dermatology and VU University Medical Center
  • Groningen, Netherlands, 9700RB
    • University Medical Center Groningen; Department of Dermatology
  • Utrecht, Netherlands, 3584 CX
    • UMC Utrecht; Dermatology
• Poland
  • Gdańsk, Poland, 80-402
    • Uniwersyteckie Centeum Kliniczne GUMed; Klinika Dermatologii, Wenerologii i Alergologii
  • Lodz, Poland, 90-265
    • DERMED Centrum Medyczne; Sp zoo
  • Szczecin, Poland, 70-322
    • Laser Clinic
  • Tarnow, Poland, 33-100
    • ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. z o. o
  • Wroclaw, Poland, 51-318
    • DERMMEDICA Sp.z o.o.
• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau; Servicio de Dermatologia
  • Madrid, Spain, 28006
    • Hospital Universitario La Princesa, Servicio dermatologia
  • Madrid, Spain, 28007
    • HUGregorio Marañón, Servicio de dermatología
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; servicio dermatologia
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz; Servicio de dermatologia
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia; servicio de dermatología
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra; Servicio de Dermatologia
• Switzerland
  • Bern, Switzerland, 3000
    • Inselspital Bern; Dermatologie
  • Lausanne, Switzerland, 1011
    • CHUV; Dermatologie
  • Zürich, Switzerland, 8091
    • Universitätsspital Zürich; Dermatologische Klinik
• Taiwan
  • Kaohsiung, Taiwan, 83301
    • Chang Gung Medical Foundation;Kaohsiung Branch; Department of Dermatology
  • Tainan, Taiwan, 70403
    • National Cheng-Kung University Hospital; Department of Dermatology
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital; Department of Dermatology
• United Kingdom
  • Dudley, United Kingdom, DY1 2HQ
    • Russells Hall Hospital
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas NHS Foundation Trust, Guys Hospital; Skin Therapy Research Unit
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Newcastle University & The Newcastle upon Tyne Hospitals NHS Foundation Trust
  • Oxford, United Kingdom, OX3 7LJ
    • Churchill Hospital
  • Poole, United Kingdom, BH15 2JB
    • Poole Hospital
  • Salford, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust
• United States
  • California
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associate
    • San Diego, California, United States, 92122
      • UCSD Division of Dermatology
    • San Francisco, California, United States, 94115
      • Univ of Calif-San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado; Anschutz Cancer Pavilion
  • Florida
    • Ormond Beach, Florida, United States, 32174
      • Ameriderm Research
    • Tampa, Florida, United States, 33609
      • Olympian Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Healthcare; Dermatology
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Troy, Michigan, United States, 48084
      • Somerset Skin Centre
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University; Dermatology
  • New York
    • New York, New York, United States, 10075
      • Sadick Research Group
  • Oregon
    • Portland, Oregon, United States, 97239-4501
      • Oregon Health & Science University; Department of Dermatology
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Medical School-Houston
    • San Antonio, Texas, United States, 78229
      • Dermatology Clinical Research Center of San Antonio
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Clinical Research Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• AD diagnosed by the Hanifin/Rajka criteria and that has been present for at least 1 year at screening
• Moderate to severe AD as graded by the Rajka/Langeland criteria at screening
• History of inadequate response to a >/= 1 month (within the 3 months prior to the screening visit) treatment regimen of at least daily TCS and regular emollient for treatment of AD
• EASI score >/= 14 at screening and end of the run-in period
• IGA score >/= 3 (5-point scale) at screening and end of the run-in period
• AD involvement of >/= 10% BSA at screening
• Pruritus VAS score >/= 3 at screening

Exclusion Criteria:

• Past and/or current use of any anti-interleukin (IL)-13 or anti-IL-4/IL-13 therapy, including lebrikizumab
• Use of an investigational agent within 4 weeks prior to screening or within 5 half-lives of the investigational agent, whichever is longer
• History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
• Use of any complementary, alternative, or homeopathic medicines including, but not limited to, phytotherapies, traditional or non-traditional herbal medications, essential fatty acids, or acupuncture within 7 days prior to the run-in period or need for such medications during the study
• Evidence of other skin conditions; including, but not limited to, T-cell lymphoma or allergic contact dermatitis
• Evidence of, or ongoing treatment (including topical antibiotics) for active skin infection at screening
• Other recent infections meeting protocol criteria
• Active tuberculosis requiring treatment within the 12 months prior to Visit 1
• Evidence of acute or chronic hepatitis or known liver cirrhosis
• Known immunodeficiency, including human immunodeficiency virus (HIV) infection
• Use of a topical calcineurin inhibitor (TCI) at the time of screening, unless the participant is willing to stop TCI use during the study (including the run-in period) and, in the investigator's opinion, it is safe to do so
• Clinically significant abnormality on screening electrocardiogram (ECG) or laboratory tests that, in the opinion of the investigator, may pose an additional risk in administering study drug or TCS to the participant
• Known current malignancy or current evaluation for a potential malignancy, including basal or squamous cell carcinoma of the skin or carcinoma in situ
• History of malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer

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
Experimental: Lebrikizumab 250 mg Single Dose + TCS Cream; Participants will receive lebrikizumab 250 milligrams (mg) SC single dose on Day 1 followed by placebo on Week 4 and Week 8. Participants will continue to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.	Drug: Lebrikizumab; Lebrikizumab will be administered SC as per the schedule specified in the respective arms.; Drug: Placebo; Placebo matching to lebrikizumab will be administered as per the schedule specified in the respective arms.; Drug: TCS Cream; TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily
Experimental: Lebrikizumab 125 mg Single Dose + TCS Cream; Participants will receive lebrikizumab 125 mg SC single dose on Day 1 followed by placebo on Week 4 and Week 8. Participants will continue to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.	Drug: Lebrikizumab; Lebrikizumab will be administered SC as per the schedule specified in the respective arms.; Drug: Placebo; Placebo matching to lebrikizumab will be administered as per the schedule specified in the respective arms.; Drug: TCS Cream; TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily
Experimental: Lebrikizumab 125 mg Q4W + TCS Cream; Participants will receive lebrikizumab 125 mg SC every 4 weeks (Q4W) for a total of 3 doses. Participants will continue to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.	Drug: Lebrikizumab; Lebrikizumab will be administered SC as per the schedule specified in the respective arms.; Drug: TCS Cream; TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily
Placebo Comparator: Placebo Q4W + TCS Cream; Participants will receive placebo Q4W for a total of 3 doses. Participants will continue to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.	Drug: Placebo; Placebo matching to lebrikizumab will be administered as per the schedule specified in the respective arms.; Drug: TCS Cream; TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Achieving a 50 Percent (%) Reduction From Baseline in Eczema Area and Severity Index (EASI) Score (EASI-50) at Week 12	Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in EASI Score at Week 12	Baseline, Week 12
Absolute Change From Baseline in EASI Score at Week 12	Baseline, Week 12
Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 12	Week 12
Percentage of Participants Achieving an Investigator's Global Assessment (IGA) score of 0 or 1 at Week 12	Week 12
Percentage of Participants With a Greater Than or Equal to (>/=) 2 Point Reduction From Baseline in IGA at Week 12	Week 12
Absolute Change From Baseline in IGA at Week 12	Baseline, Week 12
Percentage of Participants Achieving an Investigator Global Signs Assessment (IGSA) Score of 0 or 1 at Week 12	Week 12
Percentage of Participants with a >/=2 Point Reduction From Baseline in IGSA at Week 12	Week 12
Absolute Change From Baseline in IGSA at Week 12	Baseline, Week 12
Percent Change From baseline in Severity Scoring of Atopic Dermatitis (SCORAD) at Week 12	Baseline, Week 12
Absolute Change From baseline in SCORAD at Week 12	Baseline, Week 12
Percentage of Participants With a 50% or 75% Reduction From Baseline in SCORAD-50/75 at Week 12	Week 12
Percentage of Participants Achieving EASI-50 at Week 12 and Maintaining EASI-50 at Weeks 16	Weeks 12, 16
Percentage of Participants Achieving EASI-50 at Week 12 and Maintaining EASI-50 at Weeks 16 and 20	Weeks 12, 16, 20
Percentage of Participants Achieving IGA Score of 0 or 1 at Week 12 and Maintaining IGA Score of 0 or 1 at Weeks 16	Weeks 12, 16
Percentage of Participants Achieving IGA Score of 0 or 1 at Week 12 and Maintaining IGA Score of 0 or 1 at Weeks 16 and 20	Weeks 12, 16, 20
Percentage of Participants Achieving IGSA Score of 0 or 1 at Week 12 and Maintaining IGSA Score of 0 or 1 at Weeks 16	Weeks 12, 16
Percentage of Participants Achieving IGSA Score of 0 or 1 at Week 12 and Maintaining IGSA Score of 0 or 1 at Weeks 16 and 20	Weeks 12, 16, 20
Percentage of Participants Achieving SCORAD-50 at Week 12 and Maintaining SCORAD-50 at Weeks 16	Weeks 12, 16
Percentage of Participants Achieving SCORAD-50 at Week 12 and Maintaining SCORAD-50 at Weeks 16 and 20	Weeks 12, 16, 20
Percent Change From Baseline in Total % Body Surface Area (BSA) Affected At Week 12	Baseline, Week 12
Absolute Change From Baseline in Pruritus as Measured by the Pruritus Visual Analog Scale (VAS) at Week 12	Baseline, Week 12
Percent Change From Baseline in Pruritus as Measured by the Pruritus VAS at Week 12	Baseline, Week 12
Absolute Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12	Baseline, Week 12
Percent Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12	Baseline, Week 12
Total Use (Grams) of TCS From Baseline to Week 12	From Baseline to Week 12
Total Use (Grams) of TCS From Week 12 to End of Study or Early Termination	From Week 12 to end of study or early termination (up to approximately 20 weeks)
Number of Disease Flares From Baseline to Week 12	From Baseline to Week 12
Change in AD Symptoms From Baseline to Week 12, as Assessed by the Atopic Dermatitis Symptom Diary (ADSD)	Baseline, Week 12
Change in AD-Specific HealthRelated Quality of Life (QoL) From Baseline to Week 12, as Assessed by the Atopic Dermatitis Impact Questionnaire (ADIQ)	Baseline, Week 12
Change in Health-Related QoL From Baseline to Week 12, as Measured by the Dermatology Life Quality Index (DLQI)	Baseline, Week 12
Percentage of Participants With Treatment-Emergent Adverse Events (AEs)	From start of run-in period (Day -14) until study completion (up to approximately 20 Weeks)
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Lebrikizumab	Pre-dose on Days 1, 29, 85, 141, study discontinuation visit (up to Day 141)
Percentage of Participants With ATA to Phospholipase B-Like 2 (PLBL2) Protein	Pre-dose on Days 1, 29, 85, 141, study discontinuation visit (up to Day 141)
Percentage of Participants With Disease Rebound	From Week 12 up to approximately 20 weeks
Maximum Serum Concentration (Cmax) of Lebrikizumab	After first dose of lebrikizumab at Week 1
Time to Reach Cmax (Tmax) of Lebrikizumab	After first dose of lebrikizumab at Week 1
Minimum Serum Concentration (Cmin) of Lebrikizumab	Pre-dose at Weeks 4, 8, 12
Elimination Half-Life (t1/2) of Lebrikizumab	Pre-dose on Days 1, 8, 29, 43, 57, 85, 113, 141, study discontinuation visit (up to Day 141)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: January 13, 2015
• First Submitted That Met QC Criteria: January 13, 2015
• First Posted (Estimate): January 16, 2015

Study Record Updates

• Last Update Posted (Actual): October 2, 2017
• Last Update Submitted That Met QC Criteria: September 28, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• 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: GS29250; 2014-000049-56 (EudraCT Number)