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

Phase 3

Completed

• Conditions: Asthma
• Interventions: Drug: Lebrikizumab; Drug: Standard of Care; Drug: Placebo

• Registration Number: NCT01875003
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-06-07
• Study First Submitted QC: 2013-06-07
• Study First Posted: 2013-06-11
• Study Start: 2013-08-31
• Primary Completion: 2016-12-28
• Study Completion: 2016-12-28
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-15
• Last Update Posted: 2017-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 348

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lebrikizumab High	Lebrikizumab	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.
Placebo	Lebrikizumab	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.
Lebrikizumab Low	Lebrikizumab	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.
Lebrikizumab High	Standard of Care	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.
Lebrikizumab Low	Standard of Care	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.
Placebo	Standard of Care	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.
Placebo	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events (AEs) or Serious AEs	Baseline up to Week 124
Rate of Asthma Exacerbations During the 52-Week Placebo-Controlled Period	Baseline up to Week 52
Percentage of Participants With Anti-Therapeutic Antibodies to Lebrikizumab	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

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

Trial Locations

Locations (164)

Allergy Associates of Tucson; 🇺🇸 Tucson, Arizona, United States

Kaiser Permanente Los Angeles; 🇺🇸 Los Angeles, California, United States

Southern California Research Center; 🇺🇸 Mission Viejo, California, United States

Allergy & Asthma Consultants; 🇺🇸 Redwood City, California, United States

Dignity Health Medical Foundation; 🇺🇸 Sacramento, California, United States

Bensch Research Associates; 🇺🇸 Stockton, California, United States

Allergy & Asthma Medical Group; Clinical Research Division; 🇺🇸 Walnut Creek, California, United States

Colorado Children's Hospital; The Breathing Institute; 🇺🇸 Aurora, Colorado, United States

IMMUNOe International Research Centers; 🇺🇸 Centennial, Colorado, United States

Asthma & Allergy; Associates, P.C.; 🇺🇸 Colorado Springs, Colorado, United States

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