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

Phase 3TerminatedNCT01875003

Hoffmann-La Roche346 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

346

Conditions

Asthma

Interventions

Standard of CareDRUG

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

Sex: ALLMin age: 12 YearsMax age: 17 Years

Medical Language ↔ Plain English

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

Locations (81)

Southern California Research Center

Mission Viejo, California, United States

Bensch Research Associates

Stockton, California, United States

Colorado Children's Hospital; The Breathing Institute

Aurora, Colorado, United States

IMMUNOe Research Centers

Centennial, Colorado, United States

Asthma & Allergy; Associates, P.C.

Colorado Springs, Colorado, United States

Outcomes

Primary Outcomes

Rate of Asthma Exacerbations During 52-Week Placebo Controlled Period

An asthma exacerbation is defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, and/or night-time awakening due to these symptoms) that lead to treatment with systemic corticosteroids or to hospitalization. Treatment with systemic corticosteroids is defined as treatment with oral, intravenous (IV), or intramuscular (IM) corticosteroids for at least 3 days or an emergency department visit with at least 1 dose of IV or IM corticosteroids. Rate of asthma exacerbation = total number of exacerbation events divided by total follow-up time in patient years.

Time frame: Baseline up to Week 52

Secondary Outcomes

Percent Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 52

FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. The baseline FEV1 was obtained from the last spirometric analysis performed before the first study treatment administration. The percentage change in pre-bronchodilator FEV1 was defined as the change in FEV1 (in liters) from baseline divided by the FEV1 (in liters) at baseline multiplied by 100.

Time frame: Week 52

Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 52

FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. The baseline FEV1 was obtained from the last spirometric analysis performed before the first study treatment administration. Reported is the absolute change from baseline in FEV1 to the end of the placebo-controlled period at Week 52.

Time frame: Week 52

Time to First Asthma Exacerbation

An asthma exacerbation was defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, and/or night-time awakening due to these symptoms) that lead to treatment with systemic corticosteroids or to hospitalization. Treatment with systemic corticosteroids was defined as treatment with oral, IV, or IM corticosteroids for at least 3 days or an emergency department visit with at least 1 dose of IV or IM corticosteroids. Median time to first protocol-defined asthma exacerbation was estimated using Kaplan-Meier analysis. 95% Confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley.

Time frame: Baseline up to Week 52

Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 52

Measurement of FeNO (in parts per billion \[ppb\]) was performed using a hand-held portable NIOX MINO® device, in accordance with guidelines published by the American Thoracic Society (ATS) and described in the pulmonary function testing manual.

Time frame: Week 52

Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ+12) Overall Score at Week 52

The Standardized AQLQ+12 was used to assess the participants' asthma-specific health-related quality of life. The AQLQ+12 had a recall specification of 2 weeks. The AQLQ+12 was a 32-item questionnaire with 4 domains: activity limitations, symptoms, emotional function, and environmental stimuli. Each of the 32 questions were scored on a scale 1-7. The overall AQLQ+12 score is the mean of the responses to each of the 32 questions, and ranges from 1 to 7. A score 7 indicated no impairments due to asthma, and a score of 1 indicated severe impairment.

Time frame: Week 52

Change From Baseline in Asthma Rescue Medication Use at Week 52

Participants were allowed to use short-acting bronchodilators as asthma rescue medication. Baseline asthma rescue medication use was defined as the average number of puffs per day over the 7 days prior to and on the day of randomization. Participants must have recorded their asthma rescue medication use for at least 4 days to have a baseline score calculated. The post-baseline asthma medication use for any timepoint was defined as the average number of puffs per day over the last 28 days on or prior to the timepoint. Participants must have recorded their asthma rescue medication use for at least 14 days during a 28-day interval to have a score calculated for the respective timepoint. For nebulizer use, one treatment (inhalation) was considered equivalent to 4 puffs.

Time frame: Week 52

Rate of Urgent Asthma-Related Health Care Utilization (HCU) Events

Urgent asthma-related HCU events included hospitalizations, emergency department visits, and acute care visits. Rate of urgent asthma-related HCU events = total number of urgent asthma-related HCU events divided by total follow-up time in patient years.

Time frame: Baseline up to Week 52

Injection Acceptability Questionnaire (IAQ) Score

The acceptability of the injections of study drug was addressed by measuring the level of pain that participants experienced. Participants assessed pain associated with study drug administration using the IAQ within 10 minutes of study drug administration. The IAQ score ranged from 0 to 10; where 0 = no pain and 10 = worst pain imaginable.

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48

Minimum Observed Serum Concentration (Ctrough) for Lebrikizumab

Participants who received at least one dose of lebrikizumab and had at least one post-baseline evaluable sample were included in the analysis. Results of post-dose samples which were less than reportable were set to 0.045 micrograms per milliliter (mcg/mL) that is half of minimum quantifiable concentration value (0.09 mcg/mL).

Time frame: Predose (Hour 0) at Weeks 4, 12, 24, 36, and 52