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

Atopic Dermatitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02340234
• Other study ID #: GS29250
• Secondary ID: 2014-000049-56
• Status: Completed
• Phase: Phase 2
• First received: January 13, 2015
• Last updated: September 28, 2017
• Start date: May 2015
• Est. completion date: April 2016

Study information

• Verified date: September 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 212
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Lebrikizumab
Lebrikizumab will be administered SC as per the schedule specified in the respective arms.
• Placebo
Placebo matching to lebrikizumab will be administered as per the schedule specified in the respective arms.
• TCS Cream
TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily

Locations

Country	Name	City	State
Australia	Skin & Cancer Foundation	Carlton	Victoria
Australia	Fremantle Dermatology	Fremantle	Western Australia
Australia	St George Dermatology and Skin Cancer Centre	Kogarah	New South Wales
Australia	Royal Melbourne Hospital; Dermatology Department	Parkville	Victoria
Canada	Institute for Skin Advancement	Calgary	Alberta
Canada	Innovaderm Research Inc.	Montreal	Quebec
Canada	Dr. Melinda Gooderham Medicine Professional Corporation	Peterborough	Ontario
Canada	The Centre for Dermatology	Richmond Hill	Ontario
Canada	Guildford Dermatology Specialists	Surrey	British Columbia
Canada	K. Papp Clinical Research Inc.	Waterloo	Ontario
Canada	XLR8 Medical Research Inc.	Windsor	Ontario
Czechia	Faculty Hospital; Department of Dermatology	Plzen
Czechia	Charles University School of Medicine; Deptartment of Dermatology	Prague 10
Czechia	Masarykova nemocnice o.z; kozni oddeleni	Usti nad Labem
Finland	Helsinki University Central Hospital; Skin & Allergy Hospital	Helsinki
Finland	Tampere University Hospital; Dermatology and allergology	Tampere
Finland	Turku Central University Hospital; Dermatology and allergology	Turku
France	Hopital Saint Andre CHU De Bordeaux; Dermatologie	Bordeaux
France	Hopital du Bocage; Dermatologie	Dijon
France	Hopital Hotel Dieu Et Hme; Clinique Dermatologique	Nantes
France	Hopital l Archet 2; Ginestriere, Service de; Dermatologie	Nice cedex 3
France	Centre Hospitalier Lyon Sud; Dermatologie	Pierre Benite
Germany	Charite Mitte; Klinik fur Dermatologie	Berlin
Germany	Universitätsklinik Bonn	Bonn
Germany	Klinik Johann Wolfgang von Goethe Uni; Klinik für Dermatologie, Venerologie und Allergologie	Frankfurt
Germany	SRH Wald-Klinikum Gera GmbH; Hautkrankheiten und Allergologie	Gera
Germany	UKSH Kiel; Klinik für Dermatologie, Venerologie und Allergologie	Kiel
Germany	Universitätsklinikum Mainz	Mainz
Korea, Republic of	ChungAng University Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Netherlands	Academisch Medisch Centrum Universiteit Amsterdam; Dermatology and VU University Medical Center	Amsterdam
Netherlands	University Medical Center Groningen; Department of Dermatology	Groningen
Netherlands	UMC Utrecht; Dermatology	Utrecht
Poland	Uniwersyteckie Centeum Kliniczne GUMed; Klinika Dermatologii, Wenerologii i Alergologii	Gdansk
Poland	DERMED Centrum Medyczne; Sp zoo	Lodz
Poland	Laser Clinic	Szczecin
Poland	ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. z o. o	Tarnow
Poland	dermMedica sp.z o.o.	Wroclaw
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Dermatologia	Barcelona
Spain	Hospital Ramon y Cajal; servicio dermatologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de dermatologia	Madrid
Spain	Hospital Universitario La Princesa, Servicio dermatologia	Madrid
Spain	HUGregorio Marañón, Servicio de dermatología	Madrid
Spain	Clinica Universitaria de Navarra; Servicio de Dermatologia	Pamplona	Navarra
Spain	Hospital General Universitario de Valencia; servicio de dermatología	Valencia
Switzerland	Inselspital Bern; Dermatologie	Bern
Switzerland	CHUV; Dermatologie	Lausanne
Switzerland	Universitätsspital Zürich; Dermatologische Klinik	Zürich
Taiwan	Chang Gung Medical Foundation;Kaohsiung Branch; Department of Dermatology	Kaohsiung
Taiwan	National Cheng-Kung University Hospital; Department of Dermatology	Tainan
Taiwan	National Taiwan University Hospital; Department of Dermatology	Taipei
United Kingdom	Russells Hall Hospital	Dudley
United Kingdom	Guys and St Thomas NHS Foundation Trust, Guys Hospital; Skin Therapy Research Unit	London
United Kingdom	Newcastle University & The Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle upon Tyne
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Poole Hospital	Poole
United Kingdom	Salford Royal NHS Foundation Trust	Salford
United States	University of Colorado; Anschutz Cancer Pavilion	Aurora	Colorado
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Northwestern University Feinberg School Of Medicine	Chicago	Illinois
United States	University of Texas Medical School-Houston	Houston	Texas
United States	University of Iowa Healthcare; Dermatology	Iowa City	Iowa
United States	Dermatology Research Associate	Los Angeles	California
United States	Sadick Research Group	New York	New York
United States	Virginia Clinical Research Inc.	Norfolk	Virginia
United States	Ameriderm Research	Ormond Beach	Florida
United States	Oregon Health & Science University; Department of Dermatology	Portland	Oregon
United States	Washington University; Dermatology	Saint Louis	Missouri
United States	Dermatology Clinical Research Center of San Antonio	San Antonio	Texas
United States	UCSD Division of Dermatology	San Diego	California
United States	Univ of Calif-San Francisco	San Francisco	California
United States	Olympian Clinical Research	Tampa	Florida
United States	Somerset Skin Centre	Troy	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  Finland,  France,  Germany,  Korea, Republic of,  Netherlands,  Poland,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percent Change From Baseline in EASI Score at Week 12		Baseline, Week 12
Secondary	Absolute Change From Baseline in EASI Score at Week 12		Baseline, Week 12
Secondary	Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 12		Week 12
Secondary	Percentage of Participants Achieving an Investigator's Global Assessment (IGA) score of 0 or 1 at Week 12		Week 12
Secondary	Percentage of Participants With a Greater Than or Equal to (>/=) 2 Point Reduction From Baseline in IGA at Week 12		Week 12
Secondary	Absolute Change From Baseline in IGA at Week 12		Baseline, Week 12
Secondary	Percentage of Participants Achieving an Investigator Global Signs Assessment (IGSA) Score of 0 or 1 at Week 12		Week 12
Secondary	Percentage of Participants with a >/=2 Point Reduction From Baseline in IGSA at Week 12		Week 12
Secondary	Absolute Change From Baseline in IGSA at Week 12		Baseline, Week 12
Secondary	Percent Change From baseline in Severity Scoring of Atopic Dermatitis (SCORAD) at Week 12		Baseline, Week 12
Secondary	Absolute Change From baseline in SCORAD at Week 12		Baseline, Week 12
Secondary	Percentage of Participants With a 50% or 75% Reduction From Baseline in SCORAD-50/75 at Week 12		Week 12
Secondary	Percentage of Participants Achieving EASI-50 at Week 12 and Maintaining EASI-50 at Weeks 16		Weeks 12, 16
Secondary	Percentage of Participants Achieving EASI-50 at Week 12 and Maintaining EASI-50 at Weeks 16 and 20		Weeks 12, 16, 20
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of Participants Achieving SCORAD-50 at Week 12 and Maintaining SCORAD-50 at Weeks 16		Weeks 12, 16
Secondary	Percentage of Participants Achieving SCORAD-50 at Week 12 and Maintaining SCORAD-50 at Weeks 16 and 20		Weeks 12, 16, 20
Secondary	Percent Change From Baseline in Total % Body Surface Area (BSA) Affected At Week 12		Baseline, Week 12
Secondary	Absolute Change From Baseline in Pruritus as Measured by the Pruritus Visual Analog Scale (VAS) at Week 12		Baseline, Week 12
Secondary	Percent Change From Baseline in Pruritus as Measured by the Pruritus VAS at Week 12		Baseline, Week 12
Secondary	Absolute Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12		Baseline, Week 12
Secondary	Percent Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12		Baseline, Week 12
Secondary	Total Use (Grams) of TCS From Baseline to Week 12		From Baseline to Week 12
Secondary	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)
Secondary	Number of Disease Flares From Baseline to Week 12		From Baseline to Week 12
Secondary	Change in AD Symptoms From Baseline to Week 12, as Assessed by the Atopic Dermatitis Symptom Diary (ADSD)		Baseline, Week 12
Secondary	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
Secondary	Change in Health-Related QoL From Baseline to Week 12, as Measured by the Dermatology Life Quality Index (DLQI)		Baseline, Week 12
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Percentage of Participants With Disease Rebound		From Week 12 up to approximately 20 weeks
Secondary	Maximum Serum Concentration (Cmax) of Lebrikizumab		After first dose of lebrikizumab at Week 1
Secondary	Time to Reach Cmax (Tmax) of Lebrikizumab		After first dose of lebrikizumab at Week 1
Secondary	Minimum Serum Concentration (Cmin) of Lebrikizumab		Pre-dose at Weeks 4, 8, 12
Secondary	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)