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

Purpose

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.

Condition	Intervention	Phase
Asthma	Drug: Lebrikizumab Drug: Placebo Drug: Inhaled corticposteroids (ICS) Drug: Second Asthma Controller Medication	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Participant, Investigator Primary Purpose: Treatment
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

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Relative Change From Baseline in the Number of Airway Submucosal Eosinophils per Surface Area of Basal Lamina (Cells per Square Millimeter [Cells/mm^2]) [ Time Frame: From Baseline to Week 12 ]

Secondary Outcome Measures:

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


Enrollment:	64
Actual Study Start Date:	November 30, 2014
Study Completion Date:	October 13, 2016
Primary Completion Date:	October 13, 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lebrikizumab Participants with uncontrolled asthma on ICS therapy (not specified in the protocol) and a second controller medication, will receive SC injection of lebrikizumab on Days 1 and 8, and on Weeks 4 and 8.	Drug: Lebrikizumab Lebrikizumab will be administered by SC injection on Day 1, Day 8, Week 4, and Week 8. Other Name: RO5490255 Drug: 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. Drug: Second Asthma Controller Medication Participants will continue their asthma controller therapy, as they are receiving prior to screening, throughout the study.
Placebo Comparator: Placebo Participants with uncontrolled asthma on ICS therapy (not specified in the protocol) and a second controller medication, will receive SC injection of lebrikizumab matching placebo on Days 1 and 8, and on Weeks 4 and 8.	Drug: Placebo Lebrikizumab matching placebo will be administered by SC injection on Day 1, Day 8, Week 4, and Week 8. Drug: 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. Drug: Second Asthma Controller Medication Participants will continue their asthma controller therapy, as they are receiving prior to screening, throughout the study.

Arms

Assigned Interventions

Experimental: Lebrikizumab

Participants with uncontrolled asthma on ICS therapy (not specified in the protocol) and a second controller medication, will receive SC injection of lebrikizumab on Days 1 and 8, and on Weeks 4 and 8.

Drug: Lebrikizumab

Lebrikizumab will be administered by SC injection on Day 1, Day 8, Week 4, and Week 8.

Other Name: RO5490255

Drug: 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.

Drug: Second Asthma Controller Medication

Participants will continue their asthma controller therapy, as they are receiving prior to screening, throughout the study.

Placebo Comparator: Placebo

Participants with uncontrolled asthma on ICS therapy (not specified in the protocol) and a second controller medication, will receive SC injection of lebrikizumab matching placebo on Days 1 and 8, and on Weeks 4 and 8.

Drug: Placebo

Lebrikizumab matching placebo will be administered by SC injection on Day 1, Day 8, Week 4, and Week 8.

Drug: 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.

Drug: Second Asthma Controller Medication

Participants will continue their asthma controller therapy, as they are receiving prior to screening, throughout the study.

Eligibility


Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02099656

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Sponsors and Collaborators

Hoffmann-La Roche

Investigators


Study Director:	Clinical Trials	Hoffmann-La Roche

More Information


Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT02099656 History of Changes
Other Study ID Numbers:	GB29260 2014-000275-14 ( EudraCT Number )
Study First Received:	March 26, 2014
Last Updated:	May 18, 2017

Additional relevant MeSH terms:


Asthma Inflammation Bronchial Diseases Respiratory Tract Diseases Lung Diseases, Obstructive Lung Diseases Respiratory Hypersensitivity	Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Pathologic Processes Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 13, 2017