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

NCT02099656 | Completed Phase 2

• 2 other identifiers: GB292602014-000275-14
• Study Type: interventional
• Target: 64
• Locations: 6 countries
• Sites: 28

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.

Conditions

Asthma

Outcome Measures

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])

  From Baseline to Week 12

Secondary Outcomes (22)

• Absolute Change From Baseline in Number of Airway Submucosal Eosinophils per Surface Area of Basal Lamina (Cells/mm^2)

  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)

  From Baseline to Week 12

• Absolute Change From Baseline in Number of Airway Epithelial Eosinophils per Surface Area of Basal Lamina (Cells/mm^2)

  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])

  From Baseline to Week 12

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

  From Baseline to Week 12

Study Arms (2)

Lebrikizumab

EXPERIMENTAL

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; Drug: Inhaled corticposteroids (ICS); Drug: Second Asthma Controller Medication

Placebo

PLACEBO COMPARATOR

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; Drug: Inhaled corticposteroids (ICS); Drug: Second Asthma Controller Medication

Interventions

Lebrikizumab DRUG

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

Also known as: RO5490255

Lebrikizumab

Placebo DRUG

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

Placebo

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.

Lebrikizumab; Placebo

Second Asthma Controller Medication DRUG

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

Lebrikizumab; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (28)

University of Arizona

Tucson, Arizona, 85724-5030, United States

Location

LAC-USC Medical Center

Los Angeles, California, 90033, United States

Location

University of California Davis Health System; Division of Pulmonary and Critical Care Medicine

Sacramento, California, 95817, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

University of Miami School of Medicine - Sylvester at Deerfield

Deerfield Beach, Florida, Suite 200, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Iowa Hospitals & Clinics; Internal Medicine

Iowa City, Iowa, 52242, United States

Location

Brigham and Women's Hospital; Pulmonary Division

Boston, Massachusetts, 02115, United States

Location

Washington University; Pediatrics

St Louis, Missouri, 63110, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Wake Forest University Baptist Medical Center; Gastroenterology & Digestive Health

Winston-Salem, North Carolina, 27157-1045, United States

Location

Pen Memory Center

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University Hospital ; Lung Center

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh Medical Center Health System

Pittsburgh, Pennsylvania, 15213, United States

Location

UTMB Pathology Clinical Services

Galveston, Texas, 77555-0743, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Calgary

Calgary, Alberta, T2N 2T9, Canada

Location

University of Alberta Hospital-SCC/WCM

Edmonton, Alberta, T6G 2S2, Canada

Location

VGH Research Pavilion

Vancouver, British Columbia, V5Z 1L8, Canada

Location

McMaster University Health Sciences Center

Hamilton, Ontario, L8N 3Z5, Canada

Location

Hôpital Arnaud de Villeneuve

Montpellier, 34295, France

Location

Groupe Hospitalier Sud - Hôpital Haut Lévêque

Pessac, 33600, France

Location

Connolly Hospital

Dublin, 15, Ireland

Location

Skånes Universitetssjukhus, Lund

Lund, 221 85, Sweden

Location

Queen's University Belfast; NICRN Respiratory Research Office

Belfast, BT9 7AB, United Kingdom

Location

Glenfield Hospital

Leicester, LE3 9QP, United Kingdom

Location

St Mary's Hospital

London, W2 1NY, United Kingdom

Location

The Medicines Evaluation Unit

Manchester, M23 9QZ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 32909660 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

lebrikizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2014
• First Posted: March 31, 2014
• Study Start: November 6, 2014
• Primary Completion: October 13, 2016
• Study Completion: October 13, 2016
• Last Updated: September 6, 2017

Record last verified: 2017-09

Locations

GB (4); FR (2); IE (1); US (16); SE (1); CA (4)