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Completed

NCT Number: NCT02099656

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

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.

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Key information

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Calgary, Calgary, Alberta, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Lebrikizumab

Drug

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

Other names: RO5490255

Placebo

Drug

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

Inhaled corticposteroids (ICS)

Drug

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

Drug

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

Primary outcomes

  1. 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 outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. Absolute Change From Baseline in Number of Airway Submucosal Eosinophils per Volume of Submucosa (Cells/mm^3)

    Time frame: From Baseline to Week 12

  6. Relative Change From Baseline in Number of Airway Epithelial Eosinophils per Volume of Epithelium (Cells/mm^3)

    Time frame: From Baseline to Week 12

  7. Absolute Change From Baseline in Number of Airway Epithelial Eosinophils per Volume of Epithelium (Cells/mm^3)

    Time frame: Form Baseline to Week 12

  8. Change From Baseline in Blood Eosinophil Count

    Time frame: From Baseline to Week 12

  9. Change From Baseline in Immunoglobulin E (IgE) Levels

    Time frame: From Baseline to Week 12

  10. Change From Baseline in Serum Periostin Levels

    Time frame: From Baseline to Week 12

  11. Change From Baseline in Chemokine Ligand (CCL)-13 Levels

    Time frame: From Baseline to Week 12

  12. Change From Baseline in CCL-17 Levels

    Time frame: From Baseline to Week 12

  13. Change From Baseline in Lung Epithelial Cell Chloride Channel Accessory 1 (CLCA1) Gene Expression

    Time frame: From Baseline to Week 12

  14. Change From Baseline in Lung Epithelial Cell SerpinB2 Gene Expression at Week 12

    Time frame: From Baseline to Week 12

  15. Change From Baseline in Lung Epithelial Cell CCL-26 Gene Expression

    Time frame: From Baseline to Week 12

  16. Change From Baseline in Lung Epithelial Cell Nitric Oxide Synthase 2 (NOS2) Gene Expression

    Time frame: From Baseline to Week 12

  17. Change From Baseline in Lung Epithelial Cell Periostin (POSTN) Gene Expression

    Time frame: From Baseline to Week 12

  18. Relative Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)

    Time frame: From Baseline to Week 12

  19. Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)

    Time frame: From Baseline to Week 12

  20. Percentage of Participants With Treatment-Emergent Adverse Events

    Time frame: From Baseline to Week 20

  21. 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)

  22. Serum Lebrikizumab Concentration at Week 12

    Time frame: Predose (Hour 0) at Week 12

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
Mar 31, 2014
Registry last updated
Sep 6, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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