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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02099656
First Posted: March 31, 2014
Last Update Posted: September 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Hoffmann-La Roche
  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: Double (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 6, 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.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02099656


  Hide Study Locations
Locations
United States, Arizona
University of Arizona
Tucson, Arizona, United States, 85724-5030
United States, California
LAC-USC Medical Center
Los Angeles, California, United States, 90033
University of California Davis Health System; Division of Pulmonary and Critical Care Medicine
Sacramento, California, United States, 95817
United States, Connecticut
Yale School of Medicine
New Haven, Connecticut, United States, 06510
United States, Florida
University of Miami School of Medicine - Sylvester at Deerfield
Deerfield Beach, Florida, United States, Suite 200
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Iowa
University of Iowa Hospitals & Clinics; Internal Medicine
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Brigham and Women's Hospital; Pulmonary Division
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University; Pediatrics
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
Wake Forest University Baptist Medical Center; Gastroenterology & Digestive Health
Winston-Salem, North Carolina, United States, 27157-1045
United States, Pennsylvania
Pen Memory Center
Philadelphia, Pennsylvania, United States, 19104
Temple University Hospital ; Lung Center
Philadelphia, Pennsylvania, United States, 19140
University of Pittsburgh Medical Center Health System
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
UTMB Pathology Clinical Services
Galveston, Texas, United States, 77555-0743
Baylor College of Medicine
Houston, Texas, United States, 77030
Canada, Alberta
University of Calgary
Calgary, Alberta, Canada, T2N 2T9
University of Alberta Hospital-SCC/WCM
Edmonton, Alberta, Canada, T6G 2S2
Canada, British Columbia
VGH Research Pavilion
Vancouver, British Columbia, Canada, V5Z 1L8
Canada, Ontario
McMaster University Health Sciences Center
Hamilton, Ontario, Canada, L8N 3Z5
France
Hôpital Arnaud de Villeneuve
Montpellier, France, 34295
Groupe Hospitalier Sud - Hôpital Haut Lévêque
Pessac, France, 33600
Ireland
Connolly Hospital
Dublin, Ireland, 15
Sweden
Skånes Universitetssjukhus, Lund
Lund, Sweden, 221 85
United Kingdom
Queen's University Belfast; NICRN Respiratory Research Office
Belfast, United Kingdom, BT9 7AB
Glenfield Hospital
Leicester, United Kingdom, LE3 9QP
St Mary's Hospital
London, United Kingdom, W2 1NY
The Medicines Evaluation Unit
Manchester, United Kingdom, M23 9QZ
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 )
First Submitted: March 26, 2014
First Posted: March 31, 2014
Last Update Posted: September 6, 2017
Last Verified: September 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