Clinical trial NCT02340234: A Study of Lebrikizumab in Participants With Persistent Moderate to Severe Atopic Dermatitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atopic Dermatitis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-01-16
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Achieving a 50 Percent (%) Reduction From Baseline in Eczema Area and Severity Index (EASI) Score (EASI-50) at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Percent Change From Baseline in EASI Score at Week 12
timeFrame: Baseline, Week 12
measure: Absolute Change From Baseline in EASI Score at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving an Investigator's Global Assessment (IGA) score of 0 or 1 at Week 12
timeFrame: Week 12
measure: Percentage of Participants With a Greater Than or Equal to (>/=) 2 Point Reduction From Baseline in IGA at Week 12
timeFrame: Week 12
measure: Absolute Change From Baseline in IGA at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants Achieving an Investigator Global Signs Assessment (IGSA) Score of 0 or 1 at Week 12
timeFrame: Week 12
measure: Percentage of Participants with a >/=2 Point Reduction From Baseline in IGSA at Week 12
timeFrame: Week 12
measure: Absolute Change From Baseline in IGSA at Week 12
timeFrame: Baseline, Week 12
measure: Percent Change From baseline in Severity Scoring of Atopic Dermatitis (SCORAD) at Week 12
timeFrame: Baseline, Week 12
measure: Absolute Change From baseline in SCORAD at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants With a 50% or 75% Reduction From Baseline in SCORAD-50/75 at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving EASI-50 at Week 12 and Maintaining EASI-50 at Weeks 16
timeFrame: Weeks 12, 16
measure: Percentage of Participants Achieving EASI-50 at Week 12 and Maintaining EASI-50 at Weeks 16 and 20
timeFrame: Weeks 12, 16, 20
measure: Percentage of Participants Achieving IGA Score of 0 or 1 at Week 12 and Maintaining IGA Score of 0 or 1 at Weeks 16
timeFrame: Weeks 12, 16
measure: 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
timeFrame: Weeks 12, 16, 20
measure: Percentage of Participants Achieving IGSA Score of 0 or 1 at Week 12 and Maintaining IGSA Score of 0 or 1 at Weeks 16
timeFrame: Weeks 12, 16
measure: 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
timeFrame: Weeks 12, 16, 20
measure: Percentage of Participants Achieving SCORAD-50 at Week 12 and Maintaining SCORAD-50 at Weeks 16
timeFrame: Weeks 12, 16
measure: Percentage of Participants Achieving SCORAD-50 at Week 12 and Maintaining SCORAD-50 at Weeks 16 and 20
timeFrame: Weeks 12, 16, 20
measure: Percent Change From Baseline in Total % Body Surface Area (BSA) Affected At Week 12
timeFrame: Baseline, Week 12
measure: Absolute Change From Baseline in Pruritus as Measured by the Pruritus Visual Analog Scale (VAS) at Week 12
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Pruritus as Measured by the Pruritus VAS at Week 12
timeFrame: Baseline, Week 12
measure: Absolute Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12
timeFrame: Baseline, Week 12
measure: Total Use (Grams) of TCS From Baseline to Week 12
timeFrame: From Baseline to Week 12
measure: Total Use (Grams) of TCS From Week 12 to End of Study or Early Termination
timeFrame: From Week 12 to end of study or early termination (up to approximately 20 weeks)
measure: Number of Disease Flares From Baseline to Week 12
timeFrame: From Baseline to Week 12
measure: Change in AD Symptoms From Baseline to Week 12, as Assessed by the Atopic Dermatitis Symptom Diary (ADSD)
timeFrame: Baseline, Week 12
measure: Change in AD-Specific HealthRelated Quality of Life (QoL) From Baseline to Week 12, as Assessed by the Atopic Dermatitis Impact Questionnaire (ADIQ)
timeFrame: Baseline, Week 12
measure: Change in Health-Related QoL From Baseline to Week 12, as Measured by the Dermatology Life Quality Index (DLQI)
timeFrame: Baseline, Week 12
measure: Percentage of Participants With Treatment-Emergent Adverse Events (AEs)
timeFrame: From start of run-in period (Day -14) until study completion (up to approximately 20 Weeks)
measure: Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Lebrikizumab
timeFrame: Pre-dose on Days 1, 29, 85, 141, study discontinuation visit (up to Day 141)
measure: Percentage of Participants With ATA to Phospholipase B-Like 2 (PLBL2) Protein
timeFrame: Pre-dose on Days 1, 29, 85, 141, study discontinuation visit (up to Day 141)
measure: Percentage of Participants With Disease Rebound
timeFrame: From Week 12 up to approximately 20 weeks
measure: Maximum Serum Concentration (Cmax) of Lebrikizumab
timeFrame: After first dose of lebrikizumab at Week 1
measure: Time to Reach Cmax (Tmax) of Lebrikizumab
timeFrame: After first dose of lebrikizumab at Week 1
measure: Minimum Serum Concentration (Cmin) of Lebrikizumab
timeFrame: Pre-dose at Weeks 4, 8, 12
measure: Elimination Half-Life (t1/2) of Lebrikizumab
timeFrame: Pre-dose on Days 1, 8, 29, 43, 57, 85, 113, 141, study discontinuation visit (up to Day 141)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Dermatology Research Associate
state: California
city: San Diego
country: United States
facility: UCSD Division of Dermatology
state: California
city: San Francisco
country: United States
facility: Univ of Calif-San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado; Anschutz Cancer Pavilion
state: Colorado
city: Ormond Beach
country: United States
facility: Ameriderm Research
state: Florida
city: Tampa
country: United States
facility: Olympian Clinical Research
state: Florida
city: Chicago
country: United States
facility: Northwestern University Feinberg School Of Medicine
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Healthcare; Dermatology
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Troy
country: United States
facility: Somerset Skin Centre
state: Michigan
city: Saint Louis
country: United States
facility: Washington University; Dermatology
state: Missouri
city: New York
country: United States
facility: Sadick Research Group
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University; Department of Dermatology
state: Oregon
city: Houston
country: United States
facility: University of Texas Medical School-Houston
state: Texas
city: San Antonio
country: United States
facility: Dermatology Clinical Research Center of San Antonio
state: Texas
city: Norfolk
country: United States
facility: Virginia Clinical Research Inc.
state: Virginia
city: Kogarah
country: Australia
facility: St George Dermatology and Skin Cancer Centre
state: New South Wales
city: Carlton
country: Australia
facility: Skin & Cancer Foundation
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital; Dermatology Department
state: Victoria
city: Fremantle
country: Australia
facility: Fremantle Dermatology
state: Western Australia
city: Calgary
country: Canada
facility: Institute for Skin Advancement
state: Alberta
city: Surrey
country: Canada
facility: Guildford Dermatology Specialists
state: British Columbia
city: Peterborough
country: Canada
facility: Dr. Melinda Gooderham Medicine Professional Corporation
state: Ontario
city: Richmond Hill
country: Canada
facility: The Centre for Dermatology
state: Ontario
city: Waterloo
country: Canada
facility: K. Papp Clinical Research Inc.
state: Ontario
city: Windsor
country: Canada
facility: XLR8 Medical Research Inc.
state: Ontario
city: Montreal
country: Canada
facility: Innovaderm Research Inc.
state: Quebec
city: Plzen
country: Czechia
facility: Faculty Hospital; Department of Dermatology
city: Prague 10
country: Czechia
facility: Charles University School of Medicine; Deptartment of Dermatology
city: Usti nad Labem
country: Czechia
facility: Masarykova nemocnice o.z; kozni oddeleni
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital; Skin & Allergy Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital; Dermatology and allergology
city: Turku
country: Finland
facility: Turku Central University Hospital; Dermatology and allergology
city: Bordeaux
country: France
facility: Hopital Saint Andre CHU De Bordeaux; Dermatologie
city: Dijon
country: France
facility: Hopital du Bocage; Dermatologie
city: Nantes
country: France
facility: Hopital Hotel Dieu Et Hme; Clinique Dermatologique
city: Nice cedex 3
country: France
facility: Hopital l Archet 2; Ginestriere, Service de; Dermatologie
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud; Dermatologie
city: Berlin
country: Germany
facility: Charite Mitte; Klinik fur Dermatologie
city: Bonn
country: Germany
facility: Universitätsklinik Bonn
city: Frankfurt
country: Germany
facility: Klinik Johann Wolfgang von Goethe Uni; Klinik für Dermatologie, Venerologie und Allergologie
city: Gera
country: Germany
facility: SRH Wald-Klinikum Gera GmbH; Hautkrankheiten und Allergologie
city: Kiel
country: Germany
facility: UKSH Kiel; Klinik für Dermatologie, Venerologie und Allergologie
city: Mainz
country: Germany
facility: Universitätsklinikum Mainz
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: ChungAng University Hospital
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum Universiteit Amsterdam; Dermatology and VU University Medical Center
city: Groningen
country: Netherlands
facility: University Medical Center Groningen; Department of Dermatology
city: Utrecht
country: Netherlands
facility: UMC Utrecht; Dermatology
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centeum Kliniczne GUMed; Klinika Dermatologii, Wenerologii i Alergologii
city: Lodz
country: Poland
facility: DERMED Centrum Medyczne; Sp zoo
city: Szczecin
country: Poland
facility: Laser Clinic
city: Tarnow
country: Poland
facility: ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. z o. o
city: Wroclaw
country: Poland
facility: dermMedica sp.z o.o.
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra; Servicio de Dermatologia
state: Navarra
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau; Servicio de Dermatologia
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa, Servicio dermatologia
city: Madrid
country: Spain
facility: HUGregorio Marañón, Servicio de dermatología
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; servicio dermatologia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz; Servicio de dermatologia
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia; servicio de dermatología
city: Bern
country: Switzerland
facility: Inselspital Bern; Dermatologie
city: Lausanne
country: Switzerland
facility: CHUV; Dermatologie
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich; Dermatologische Klinik
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation;Kaohsiung Branch; Department of Dermatology
city: Tainan
country: Taiwan
facility: National Cheng-Kung University Hospital; Department of Dermatology
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital; Department of Dermatology
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust, Guys Hospital; Skin Therapy Research Unit
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle University & The Newcastle upon Tyne Hospitals NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Poole
country: United Kingdom
facility: Poole Hospital
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: