Overview

This trial is active, not recruiting.

Condition asthma
Treatments lebrikizumab, placebo
Phase phase 3
Sponsor Hoffmann-La Roche
Start date July 2013
End date January 2017
Trial size 1081 participants
Trial identifier NCT01867125, 2013-000175-33, GB28688

Summary

This randomized, multicenter, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of lebrikizumab in participants with asthma whose disease remains uncontrolled despite daily treatment with inhaled corticosteroid (ICS) therapy and at least one second controller medication. Participants will be randomized in 1:1:1 ratio to receive double-blind treatment with either lebrikizumab ("high" or "low") or placebo, administered subcutaneously (SC) every 4 weeks for 52 weeks, in addition to their standard-of-care therapy. This will be followed by a 52-week double-blind active treatment extension. During double-blind active treatment extension period, all participants will receive SC injection of lebrikizumab from Week 53 to Week 104. The anticipated time on study treatment is 104 weeks. After study treatment, all participants will complete a 20-week safety follow-up.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
Participants will receive SC injection of lebrikizumab (125 milligrams [mg]) every 4 weeks for 104 weeks.
lebrikizumab RO5490255
Lebrikizumab will be administered as SC injection at 125 or 37.5 mg every 4 weeks, for 104 weeks.
(Experimental)
Participants will receive SC injection of lebrikizumab (37.5 mg) every 4 weeks for 104 weeks.
lebrikizumab RO5490255
Lebrikizumab will be administered as SC injection at 125 or 37.5 mg every 4 weeks, for 104 weeks.
placebo
Lebrikizumab matching placebo will be administered as SC injection every 4 weeks for 52 weeks.
(Placebo Comparator)
Participants will receive SC injection of lebrikizumab matching placebo every 4 weeks for 52 weeks during placebo-controlled period and then SC injection of lebrikizumab at 125 or 37.5 mg for 52 weeks during active treatment extension period.
lebrikizumab RO5490255
Lebrikizumab will be administered as SC injection at 125 or 37.5 mg every 4 weeks, for 104 weeks.
placebo
Lebrikizumab matching placebo will be administered as SC injection every 4 weeks for 52 weeks.

Primary Outcomes

Measure
Rate of Asthma Exacerbations During the 52-Week Placebo-Controlled Period
time frame: Baseline up to 52 weeks

Secondary Outcomes

Measure
Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
time frame: Baseline, Week 52
Time to First Asthma Exacerbation
time frame: Baseline up to 52 weeks
Change From Baseline in Standardized Asthma Quality of Life Questionnaire (AQLQ) Score
time frame: Baseline, Week 52
Change from Baseline In Asthma Rescue Medication (Number of Puffs or Nebulized Treatments)
time frame: Baseline, Week 52
Rate of Urgent Asthma-Related Urgent Health Care Utilization
time frame: Baseline up to Week 52
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, 64, 76, 92, 104, 112, and 124)
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score
time frame: Baseline, Week 52
Percentage of Participants With Adverse Events
time frame: Baseline, Week 124
Minimum Serum Concentration (Cmin) of Lebrikizumab
time frame: Predose (0 hour) on Weeks 4, 12, 24, 36, and 52

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

Inclusion Criteria: - Asthma diagnosis for greater than equal to (>/=) 12 months prior to Visit 1 - Bronchodilator response at Visit 1, 2, or 3 - 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 micrograms (mcg) of fluticasone propionate dry powder inhaler (DPI) or equivalent for >/=6 months prior to Visit 1 - On an eligible second controller medication (long-acting beta-agonist [LABA], leukotriene receptor antagonist [LTRA], long-acting muscarinic antagonist [LAMA], or theophylline) for 6 months prior to Visit 1 - Uncontrolled asthma at Visit 1 and/or Visit 2, and at Visit 3 - Chest X-ray or computed tomography (CT) scan within 3 months prior to Visit 1 or chest X-ray during the screening period (prior to Visit 3) confirming the absence of other clinically significant lung disease - 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 of 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 requiring hospital admission for >/=24 hours or requiring treatment with IV or IM antibiotics within 4 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 infection that required treatment with oral antibiotics within 2 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 - Active tuberculosis requiring treatment within 12 months prior to Visit 1 - Known immunodeficiency, including, but not limited to, human immunodeficiency virus (HIV) infection - Evidence of acute or chronic hepatitis or known liver cirrhosis - 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 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 prior to Visit 1 (whichever is longer) or during screening - Initiation of or change in allergen immunotherapy within 3 months prior to Visit 1 or during screening

Additional Information

Official title A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Lebrikizumab in Patients With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and a Second Controller Medication
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.