A Study of Lebrikizumab in Adolescent Participants With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and a Second Controller Medication - Full Text View

Purpose

This randomized, multicenter, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy, safety, and tolerability of lebrikizumab in adolescent participants with asthma whose disease remains uncontrolled despite daily treatment with inhaled corticosteroids (ICS) therapy and at least one second controller medication. Participants will be randomized in a 1:1:1 ratio to receive double-blind treatment with either lebrikizumab ('High' or 'Low') or placebo, administered as subcutaneous (SC) every 4 weeks (Q4W) for 52 weeks, in addition to their standard-of-care therapy. This will be followed by an optional 52-week double-blind active-treatment extension. The anticipated time on study treatment is up to 104 weeks. Participants who complete the study to Week 104, discontinue prematurely or decide not to take part in the optional active-treatment extension will transition to the 20-week safety follow-up period.

Condition	Intervention	Phase
Asthma	Drug: Lebrikizumab Drug: Placebo Drug: Standard of Care	Phase 3


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

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Rate of Asthma Exacerbations During the 52-Week Placebo-Controlled Period [ Time Frame: Baseline up to Week 52 ]
Percentage of Participants With Adverse Events (AEs) or Serious AEs [ Time Frame: Baseline up to Week 124 ]
Percentage of Participants With Anti-Therapeutic Antibodies to Lebrikizumab [ Time Frame: Baseline up to Week 124 (assessed at Baseline, Weeks 4, 12, 24, 36, 52, 76, 104, 112, and 124 or at early termination [up to 108 weeks]) ]

Secondary Outcome Measures:

Change from Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 second (FEV1) at Week 52 [ Time Frame: Baseline , Week 52 ]
Time to First Asthma Exacerbation [ Time Frame: Baseline up to 52 weeks ]
Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 52 [ Time Frame: Baseline , Week 52 ]
Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and Older (AQLQ + 12) at Week 52 [ Time Frame: Baseline, Week 52 ]
Change From Baseline in Asthma Rescue Medication Use at Week 52 [ Time Frame: Baseline, Week 52 ]
Rate of Urgent Asthma-Related Health Care Utilization [ Time Frame: Baseline up to 52 weeks ]
Injection Acceptability Questionnaire (IAQ) Score [ Time Frame: Baseline up to Week 104 ]


Enrollment:	348
Actual Study Start Date:	August 31, 2013
Study Completion Date:	December 28, 2016
Primary Completion Date:	December 28, 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lebrikizumab High Participants with uncontrolled asthma on ICS therapy (total daily dose of 500−2000 micrograms [mcg] of fluticasone propionate dry powder inhaler [DPI] or equivalent) and a second controller medication, will receive SC injection of lebrikizumab (high dose) Q4W for 52 weeks during placebo-controlled period and up to 76 weeks or 104 weeks for participants who will be willing to take part in optional active-treatment extension period.	Drug: Lebrikizumab Lebrikizumab will be administered as SC injection at high or low dose Q4W. Drug: Standard of Care Participants will continue to receive ICS therapy (total daily dose of 500-2000 mcg fluticasone propionate DPI or equivalent) along with at least one second controller medications (e.g. long-acting beta agonists [LABAs], leukotriene receptor antagonists (LTRAs), long-acting muscarinic antagonists (LAMAs), or theophylline) as standard of care.
Experimental: Lebrikizumab Low Participants with uncontrolled asthma on ICS therapy (total daily dose of 500−2000 mcg of fluticasone propionate DPI or equivalent) and a second controller medication, will receive SC injection of lebrikizumab (low dose) Q4W for 52 weeks during placebo-controlled period and up to 76 weeks or 104 weeks for participants who will be willing to take part in optional active-treatment extension period.	Drug: Lebrikizumab Lebrikizumab will be administered as SC injection at high or low dose Q4W. Drug: Standard of Care Participants will continue to receive ICS therapy (total daily dose of 500-2000 mcg fluticasone propionate DPI or equivalent) along with at least one second controller medications (e.g. long-acting beta agonists [LABAs], leukotriene receptor antagonists (LTRAs), long-acting muscarinic antagonists (LAMAs), or theophylline) as standard of care.
Placebo Comparator: Placebo Participants with uncontrolled asthma on ICS therapy (total daily dose of 500−2000 mcg of fluticasone propionate DPI or equivalent) and a second controller medication, will receive SC injection of lebrikizumab matching placebo Q4W for 52 weeks during placebo-controlled period and then SC injection of lebrikizumab at high or low dose will be administered from Weeks 52 to 76 or 104 to participants who are willing to take part in optional active-treatment extension period.	Drug: Lebrikizumab Lebrikizumab will be administered as SC injection at high or low dose Q4W. Drug: Placebo Lebrikizumab matching placebo will be administered as SC injection Q4W. Drug: Standard of Care Participants will continue to receive ICS therapy (total daily dose of 500-2000 mcg fluticasone propionate DPI or equivalent) along with at least one second controller medications (e.g. long-acting beta agonists [LABAs], leukotriene receptor antagonists (LTRAs), long-acting muscarinic antagonists (LAMAs), or theophylline) as standard of care.

Eligibility


Ages Eligible for Study:	12 Years to 17 Years (Child)
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 during screening
Pre-bronchodilator FEV1 of 40 percent (%) - 90% predicted at both Visits 2 and 3
On high dose ICS therapy for >/= 6 months prior to Visit 1
On an eligible second controller medication for 6 months prior to Visit 1
Uncontrolled asthma as defined by the protocol both during screening and at the time of randomization
Demonstrated adherence with controller medication during the screening period

Exclusion Criteria:

History of severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
Maintenance oral corticosteroid therapy within 3 months prior to Visit 1
Treatment with systemic (oral, intravenous [IV], or intramuscular [IM]) corticosteroids within 4 weeks prior to Visit 1 or during the screening period
Treatment with intra-articular corticosteroids within 4 weeks prior to Visit 1 or during the screening period or anticipated need for intra-articular corticosteroids during the course of the study
Infection that meets the following criteria: Any infection requiring hospital admission or requiring treatment with IV or IM antibiotics within 4 weeks prior to Visit 1 or during screening; any active infection that required treatment with oral antibiotics within 2 weeks prior to Visit 1 or during screening; upper or lower respiratory tract infection within 4 weeks prior to Visit 1 or during screening; active parasitic infection or Listeria monocytogenes infection within 6 months prior to Visit 1 or during screening
History of active tuberculosis requiring treatment
Known immunodeficiency, including, but not limited to, human immunodeficiency virus (HIV) infection
Evidence of acute or chronic hepatitis or known liver cirrhosis
History of cystic fibrosis, bronchiectasis, and/or other clinically significant lung disease other than asthma
Diagnosis or history of malignancy or current evaluation for potential malignancy
Current smoker or former smoker with a history of greater than (>) 10 pack-years
History of alcohol or drug abuse
Past and/or current use of any anti- interleukin (IL) -13 or anti-IL-4/IL-13 therapy, including lebrikizumab
Use of other monoclonal antibody therapy, including omalizumab, within 6 months or 5 drug half-lives (whichever is longer) prior to Visit 1
Initiation of or change in allergen immunotherapy within 3 months prior to Visit 1 or during screening
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: NCT01875003

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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:	NCT01875003 History of Changes
Other Study ID Numbers:	WB28183 2012-000180-25 ( EudraCT Number )
Study First Received:	June 7, 2013
Last Updated:	May 15, 2017


Studies a U.S. FDA-regulated Drug Product:		Yes

Additional relevant MeSH terms:


Asthma Bronchial Diseases Respiratory Tract Diseases Lung Diseases, Obstructive Lung Diseases Respiratory Hypersensitivity Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Fluticasone Antibodies, Monoclonal	Anti-Inflammatory Agents Bronchodilator Agents Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Asthmatic Agents Respiratory System Agents Dermatologic Agents Anti-Allergic Agents Immunologic Factors

ClinicalTrials.gov processed this record on July 13, 2017