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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT02099656

Collaborator

(none)

Enrollment

Locations

Arms

23.2

Actual Duration (Months)

2.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

64 participants

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

Actual Study Start Date :

Nov 6, 2014

Actual Primary Completion Date :

Oct 13, 2016

Actual Study Completion Date :

Oct 13, 2016

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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.

Arm

Intervention/Treatment

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 Names:

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.

Outcome Measures

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]) [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) [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]
Relative Change From Baseline in Number of Airway Epithelial Eosinophils per Volume of Epithelium (Cells/mm^3) [From Baseline to Week 12]
Absolute Change From Baseline in Number of Airway Epithelial Eosinophils per Volume of Epithelium (Cells/mm^3) [Form Baseline to Week 12]
Change From Baseline in Blood Eosinophil Count [From Baseline to Week 12]
Change From Baseline in Immunoglobulin E (IgE) Levels [From Baseline to Week 12]
Change From Baseline in Serum Periostin Levels [From Baseline to Week 12]
Change From Baseline in Chemokine Ligand (CCL)-13 Levels [From Baseline to Week 12]
Change From Baseline in CCL-17 Levels [From Baseline to Week 12]
Change From Baseline in Lung Epithelial Cell Chloride Channel Accessory 1 (CLCA1) Gene Expression [From Baseline to Week 12]
Change From Baseline in Lung Epithelial Cell SerpinB2 Gene Expression at Week 12 [From Baseline to Week 12]
Change From Baseline in Lung Epithelial Cell CCL-26 Gene Expression [From Baseline to Week 12]
Change From Baseline in Lung Epithelial Cell Nitric Oxide Synthase 2 (NOS2) Gene Expression [From Baseline to Week 12]
Change From Baseline in Lung Epithelial Cell Periostin (POSTN) Gene Expression [From Baseline to Week 12]
Relative Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) [From Baseline to Week 12]
Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) [From Baseline to Week 12]
Percentage of Participants With Treatment-Emergent Adverse Events [From Baseline to Week 20]
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)]
Serum Lebrikizumab Concentration at Week 12 [Predose (Hour 0) at Week 12]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT02099656

Other Study ID Numbers:

GB29260
2014-000275-14

First Posted:

Mar 31, 2014

Last Update Posted:

Sep 6, 2017

Last Verified:

Sep 1, 2017

Additional relevant MeSH terms:

Asthma

Inflammation

Study Results

No Results Posted as of Sep 6, 2017