Clinical trial NCT02099656: A Study Evaluating the Effects of Lebrikizumab on Airway Eosinophilic Inflammation in Participants With Uncontrolled Asthma
Official title: A Phase II, Randomized, Double-Blind, Placebo-Controlled Bronchoscopy Study to Evaluate the Effects of Lebrikizumab on Airway Eosinophilic Inflammation in Patients With Uncontrolled Asthma on Inhaled Corticosteroids and a Second Controller Medication
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-03-31
Enrollment: 64
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 Phase II, randomized, double-blind, placebo-controlled, multicenter study will evaluate the effects of lebrikizumab on airway eosinophilic inflammation in participants with uncontrolled asthma who are using inhaled corticosteroid (ICS) treatment and a second controller medication. Enrolled participants will undergo a 3-week screening period during which assessments, including a bronchoscopy procedure, will be made. Participants will subsequently be randomized to receive lebrikizumab or placebo by subcutaneous (SC) injection on Day 1, Day 8, Week 4, and Week 8. Participants will continue their standard of care therapy throughout the study. End of treatment assessments will be taken at Week 12. Total study period, including screening and follow-up, is expected to last 23 weeks.


Eligibility criteria: Inclusion Criteria:

* Asthma diagnosis for greater than or equal to (\>/=) 12 months prior to Visit 1
* Bronchodilator response demonstrated within the 12 months before Visit 1 or at Visit 1, 2, or 3 of screening
* Pre-bronchodilator FEV1 of 40 percent (%) - 80% predicted at both Visits 2 and 3
* On ICS therapy at a total daily dose of 500-2000 mcg of fluticasone propionate dry powder inhaler (DPI) or equivalent for \>/= 6 months prior to Visit 1, with no changes within 4 weeks prior to Visit 1, and no anticipated changes throughout the study
* On an eligible second controller medication (long-acting Beta-agonist \[LABA), leukotriene receptor antagonist \[LTRA\], long-acting muscarinic antagonists \[LAMAs\] or theophylline) for 6 months prior to Visit 1, with no changes within 4 weeks prior to Visit 1, and no anticipated changes throughout the study
* Uncontrolled asthma at Visit 1 and/or 2 and at Visit 3
* Chest X-ray or computed tomography (CT) scan within 12 months prior to Visit 1 or chest X-ray during the screening period (prior to Visit 3) that confirms the absence of other clinically significant lung disease
* Demonstrated adherence with controller medication during the screening period

Exclusion Criteria:

* Maintenance oral corticosteroid therapy, defined as daily alternate-day oral corticosteroid maintenance therapy within 3 months prior to Visit 1
* Treatment with systemic corticosteroids within 4 weeks prior to Visit 1 or during the screening period for any reason, including an acute exacerbation event
* Any infection requiring hospital, intravenous (IV) or intramuscular (IM) antibiotic treatment or any respiratory infection within 4 weeks prior to Visit 1 or during screening. Any infection requiring oral antibiotic treatment with 2 weeks prior to Visit 1 or during screening, or any parasitic infection within 6 months prior to Visit 1 or during screening
* Active tuberculosis requiring treatment within 12 months prior to Visit 1
* Known immunodeficiency, including, but not limited to, human immunodeficiency virus (HIV) infection
* History of interstitial lung disease, chronic obstructive pulmonary disease (COPD), or other clinically significant lung disease other than asthma
* Known current malignancy or current evaluation for a potential malignancy
* Unable to safely undergo elective flexible fiberoptic bronchoscopy
* Clinically significant medical disease that is uncontrolled despite treatment, that is likely, in the opinion of the investigator, to impact the participant's ability to participate in the study, or to impact the study assessments
* History of alcohol or drug abuse that would impair or risk the participant's full participation in the study, in the opinion of the investigator
* Current smoker or history of smoking (greater than \[\>\] 10 pack-years), or unwillingness to abstain from smoking for the duration of the study
* Past and/or current use of any anti-interleukin (IL)-13 or anti-IL-4/IL-13 therapy, including lebrikizumab
* Use of a licensed or investigational monoclonal antibody other than anti-IL-13, or anti IL-4/IL-13, including, but not limited to, omalizumab, anti-IL-5, or anti-IL-17, within 6 months or 5 drug half-lives prior to Visit 1 (whichever is longer) or during screening
* Use of a systemic immunomodulatory or immunosuppressive therapy within 3 months or 5 drug half-lives prior to Visit 1 (whichever is longer) or during screening
* Use of other investigational therapy within 4 weeks or 5 drug half-lives prior to Visit 1 (whichever is longer) or during screening
* Initiation of or increase in allergen immunotherapy within 3 months prior to Visit 1 or during screening
* Body mass index \>38 kilograms per square meter (kg/m\^2)
* Body weight \<40 kilograms (kg)
* History of bronchial thermoplasty

Primary outcomes:
measure: Relative Change From Baseline in the Number of Airway Submucosal Eosinophils per Surface Area of Basal Lamina (Cells per Square Millimeter [Cells/mm^2])
timeFrame: From Baseline to Week 12
Secondary outcomes:
measure: Absolute Change From Baseline in Number of Airway Submucosal Eosinophils per Surface Area of Basal Lamina (Cells/mm^2)
timeFrame: From Baseline to Week 12
measure: Relative Change From Baseline in the Number of Airway Epithelial Eosinophils per Surface Area of Basal Lamina (Cells/mm^2)
timeFrame: From Baseline to Week 12
measure: Absolute Change From Baseline in Number of Airway Epithelial Eosinophils per Surface Area of Basal Lamina (Cells/mm^2)
timeFrame: From Baseline to Week 12
measure: Relative Change From Baseline in Number of Airway Submucosal Eosinophils per Volume of Submucosa (Cells per Cubic Millimeter [Cells/mm^3])
timeFrame: From Baseline to Week 12
measure: Absolute Change From Baseline in Number of Airway Submucosal Eosinophils per Volume of Submucosa (Cells/mm^3)
timeFrame: From Baseline to Week 12
measure: Relative Change From Baseline in Number of Airway Epithelial Eosinophils per Volume of Epithelium (Cells/mm^3)
timeFrame: From Baseline to Week 12
measure: Absolute Change From Baseline in Number of Airway Epithelial Eosinophils per Volume of Epithelium (Cells/mm^3)
timeFrame: Form Baseline to Week 12
measure: Change From Baseline in Blood Eosinophil Count
timeFrame: From Baseline to Week 12
measure: Change From Baseline in Immunoglobulin E (IgE) Levels
timeFrame: From Baseline to Week 12
measure: Change From Baseline in Serum Periostin Levels
timeFrame: From Baseline to Week 12
measure: Change From Baseline in Chemokine Ligand (CCL)-13 Levels
timeFrame: From Baseline to Week 12
measure: Change From Baseline in CCL-17 Levels
timeFrame: From Baseline to Week 12
measure: Change From Baseline in Lung Epithelial Cell Chloride Channel Accessory 1 (CLCA1) Gene Expression
timeFrame: From Baseline to Week 12
measure: Change From Baseline in Lung Epithelial Cell SerpinB2 Gene Expression at Week 12
timeFrame: From Baseline to Week 12
measure: Change From Baseline in Lung Epithelial Cell CCL-26 Gene Expression
timeFrame: From Baseline to Week 12
measure: Change From Baseline in Lung Epithelial Cell Nitric Oxide Synthase 2 (NOS2) Gene Expression
timeFrame: From Baseline to Week 12
measure: Change From Baseline in Lung Epithelial Cell Periostin (POSTN) Gene Expression
timeFrame: From Baseline to Week 12
measure: Relative Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)
timeFrame: From Baseline to Week 12
measure: Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: From Baseline to Week 12
measure: Percentage of Participants With Treatment-Emergent Adverse Events
timeFrame: From Baseline to Week 20
measure: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Lebrikizumab
timeFrame: Baseline up to Week 20 (assessed at Baseline, Weeks 8 and 20/dosing termination or early termination)
measure: Serum Lebrikizumab Concentration at Week 12
timeFrame: Predose (Hour 0) at Week 12
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: LAC-USC Medical Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Health System; Division of Pulmonary and Critical Care Medicine
state: California
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Deerfield Beach
country: United States
facility: University of Miami School of Medicine - Sylvester at Deerfield
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics; Internal Medicine
state: Iowa
city: Boston
country: United States
facility: Brigham and Women's Hospital; Pulmonary Division
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University; Pediatrics
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center; Gastroenterology & Digestive Health
state: North Carolina
city: Philadelphia
country: United States
facility: Pen Memory Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital ; Lung Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Health System
state: Pennsylvania
city: Galveston
country: United States
facility: UTMB Pathology Clinical Services
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital-SCC/WCM
state: Alberta
city: Vancouver
country: Canada
facility: VGH Research Pavilion
state: British Columbia
city: Hamilton
country: Canada
facility: McMaster University Health Sciences Center
state: Ontario
city: Montpellier
country: France
facility: Hôpital Arnaud de Villeneuve
city: Pessac
country: France
facility: Groupe Hospitalier Sud - Hôpital Haut Lévêque
city: Dublin
country: Ireland
facility: Connolly Hospital
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus, Lund
city: Belfast
country: United Kingdom
facility: Queen's University Belfast; NICRN Respiratory Research Office
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
city: London
country: United Kingdom
facility: St Mary's Hospital
city: Manchester
country: United Kingdom
facility: The Medicines Evaluation Unit
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Austin CD, Gonzalez Edick M, Ferrando RE, Solon M, Baca M, Mesh K, Bradding P, Gauvreau GM, Sumino K, FitzGerald JM, Israel E, Bjermer L, Bourdin A, Arron JR, Choy DF, Olsson JK, Abreu F, Howard M, Wong K, Cai F, Peng K, Putnam WS, Holweg CTJ, Matthews JG, Kraft M, Woodruff PG; CLAVIER Investigators. A randomized, placebo-controlled trial evaluating effects of lebrikizumab on airway eosinophilic inflammation and remodelling in uncontrolled asthma (CLAVIER). Clin Exp Allergy. 2020 Dec;50(12):1342-1351. doi: 10.1111/cea.13731. Epub 2020 Oct 4.