A Study Evaluating the Effects of Lebrikizumab on Airway Eosinophilic Inflammation in Participants With Uncontrolled Asthma

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02099656
• Other study ID #: GB29260
• Secondary ID: 2014-000275-14
• Status: Completed
• Phase: Phase 2
• First received: March 26, 2014
• Last updated: September 4, 2017
• Start date: November 6, 2014
• Est. completion date: October 13, 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: October 13, 2016
• Est. primary completion date: October 13, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma
• Inflammation

Intervention

Drug:
• Lebrikizumab
Lebrikizumab will be administered by SC injection on Day 1, Day 8, Week 4, and Week 8.
• Placebo
Lebrikizumab matching placebo will be administered by SC injection on Day 1, Day 8, Week 4, and Week 8.
• Inhaled corticposteroids (ICS)
Participants will continue their ICS controller therapy, as they are receiving prior to screening, throughout the study. Protocol does not specify any particular ICS.
• Second Asthma Controller Medication
Participants will continue their asthma controller therapy, as they are receiving prior to screening, throughout the study.

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	University of Alberta Hospital-SCC/WCM	Edmonton	Alberta
Canada	McMaster University Health Sciences Center	Hamilton	Ontario
Canada	VGH Research Pavilion	Vancouver	British Columbia
France	Hôpital Arnaud de Villeneuve	Montpellier
France	Groupe Hospitalier Sud - Hôpital Haut Lévêque	Pessac
Ireland	Connolly Hospital	Dublin
Sweden	Skånes Universitetssjukhus, Lund	Lund
United Kingdom	Queen's University Belfast; NICRN Respiratory Research Office	Belfast
United Kingdom	Glenfield Hospital	Leicester
United Kingdom	St Mary's Hospital	London
United Kingdom	The Medicines Evaluation Unit	Manchester
United States	Brigham and Women's Hospital; Pulmonary Division	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	University of Miami School of Medicine - Sylvester at Deerfield	Deerfield Beach	Florida
United States	Duke University Medical Center	Durham	North Carolina
United States	UTMB Pathology Clinical Services	Galveston	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	University of Iowa Hospitals & Clinics; Internal Medicine	Iowa City	Iowa
United States	LAC-USC Medical Center	Los Angeles	California
United States	Yale School of Medicine	New Haven	Connecticut
United States	Pen Memory Center	Philadelphia	Pennsylvania
United States	Temple University Hospital ; Lung Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center Health System	Pittsburgh	Pennsylvania
United States	University of California Davis Health System; Division of Pulmonary and Critical Care Medicine	Sacramento	California
United States	Washington University; Pediatrics	Saint Louis	Missouri
United States	University of Arizona	Tucson	Arizona
United States	Wake Forest University Baptist Medical Center; Gastroenterology & Digestive Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Canada,  France,  Ireland,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative Change From Baseline in the Number of Airway Submucosal Eosinophils per Surface Area of Basal Lamina (Cells per Square Millimeter [Cells/mm^2])		From Baseline to Week 12
Secondary	Absolute Change From Baseline in Number of Airway Submucosal Eosinophils per Surface Area of Basal Lamina (Cells/mm^2)		From Baseline to Week 12
Secondary	Relative Change From Baseline in the Number of Airway Epithelial Eosinophils per Surface Area of Basal Lamina (Cells/mm^2)		From Baseline to Week 12
Secondary	Absolute Change From Baseline in Number of Airway Epithelial Eosinophils per Surface Area of Basal Lamina (Cells/mm^2)		From Baseline to Week 12
Secondary	Relative Change From Baseline in Number of Airway Submucosal Eosinophils per Volume of Submucosa (Cells per Cubic Millimeter [Cells/mm^3])		From Baseline to Week 12
Secondary	Absolute Change From Baseline in Number of Airway Submucosal Eosinophils per Volume of Submucosa (Cells/mm^3)		From Baseline to Week 12
Secondary	Relative Change From Baseline in Number of Airway Epithelial Eosinophils per Volume of Epithelium (Cells/mm^3)		From Baseline to Week 12
Secondary	Absolute Change From Baseline in Number of Airway Epithelial Eosinophils per Volume of Epithelium (Cells/mm^3)		Form Baseline to Week 12
Secondary	Change From Baseline in Blood Eosinophil Count		From Baseline to Week 12
Secondary	Change From Baseline in Immunoglobulin E (IgE) Levels		From Baseline to Week 12
Secondary	Change From Baseline in Serum Periostin Levels		From Baseline to Week 12
Secondary	Change From Baseline in Chemokine Ligand (CCL)-13 Levels		From Baseline to Week 12
Secondary	Change From Baseline in CCL-17 Levels		From Baseline to Week 12
Secondary	Change From Baseline in Lung Epithelial Cell Chloride Channel Accessory 1 (CLCA1) Gene Expression		From Baseline to Week 12
Secondary	Change From Baseline in Lung Epithelial Cell SerpinB2 Gene Expression at Week 12		From Baseline to Week 12
Secondary	Change From Baseline in Lung Epithelial Cell CCL-26 Gene Expression		From Baseline to Week 12
Secondary	Change From Baseline in Lung Epithelial Cell Nitric Oxide Synthase 2 (NOS2) Gene Expression		From Baseline to Week 12
Secondary	Change From Baseline in Lung Epithelial Cell Periostin (POSTN) Gene Expression		From Baseline to Week 12
Secondary	Relative Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)		From Baseline to Week 12
Secondary	Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)		From Baseline to Week 12
Secondary	Percentage of Participants With Treatment-Emergent Adverse Events		From Baseline to Week 20
Secondary	Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Lebrikizumab		Baseline up to Week 20 (assessed at Baseline, Weeks 8 and 20/dosing termination or early termination)
Secondary	Serum Lebrikizumab Concentration at Week 12		Predose (Hour 0) at Week 12