Clinical trial NCT01545440: A Study of Lebrikizumab in Patients Whose Asthma is Uncontrolled With Inhaled Corticosteroids and A Second Controller Medication (LUTE)
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Lebrikizumab in Patients With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and A Second Controller Medication
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2012-03-06
Enrollment: 258
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized, multicenter, double-blind, placebo-controlled, parallel-group study will assess the efficacy and safety of lebrikizumab in patients with asthma whose disease remains uncontrolled despite daily therapy with an inhaled corticosteroid and a second controller medication. Patients will be randomized in a 1:1:1:1 ratio to receive double-blind treatment with subcutaneous lebrikizumab ("highest", "middle", "lowest" dose) or placebo 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. The anticipated time on study treatment is up to 104 weeks. There will be a safety follow-up of 24 weeks after the last dose of study drug for all patients.


Eligibility criteria: Inclusion Criteria:

* Adult patients, 18 to 75 years of age at Visit 1
* Asthma diagnosis for \>/= 12 months prior to the start of screening (Visit 1)
* Bronchodilator response during screening
* Pre-bronchodilator FEV1 40%-80% of predicted during screening
* On ICS (inhaled corticosteroids) 500-2000 mcg/day of fluticasone propionate DPI or equivalent for \>/= 6 months prior to the start of screening (Visit 1) with no anticipated changes throughout the study
* On an eligible second controller medication (LABA, LAMA, LTRA or theophylline within the prescribed dosing range)
* Uncontrolled asthma as defined by protocol both during screening period and at time of randomization
* Chest X-ray or computed tomography (CT) scan obtained within 12 months prior to screening or chest X-ray during screening period confirming the absence of other lung disease
* Demonstrated adherence with controller medication during the screening period

Exclusion Criteria:

* History of severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
* Use of zileuton or roflumilast within 6 months prior to screening
* Maintenance oral corticosteroid therapy, defined as daily or alternate day oral corticosteroid maintenance therapy within the 3 months prior to Visit 1
* Treatment with systemic (oral, intravenous or intramuscular) corticosteroids within the 4 weeks prior to Visit 1
* Major episode of infection within 4 weeks prior to Visit 1 or treatment with oral antibiotics within 2 weeks prior to Visit 1
* Active parasitic infection within the 6 months prior to Visit 1
* Active tuberculosis requiring treatment within the 12 months prior to Visit 1
* Known immunodeficiency, including, but not limited to, HIV infection
* Evidence of acute or chronic hepatitis or known liver cirrhosis
* History of cystic fibrosis, chronic obstructive pulmonary disease, and/or other clinically significant lung disease other than asthma
* Known malignancy or current evaluation for a potential malignancy
* Current smoker or former smoker with a history \>10 pack years
* History of alcohol, drug or chemical abuse
* Initiation or change in allergen immunotherapy within 3 months prior to Visit 1
* Use of biologic therapy including omalizumab during 6 months prior to Visit 1
* Receipt of live/attenuated vaccine within 4 weeks prior to Visit 1
* Pregnant or lactating women
* Body mass index (BMI) \> 38 kg/m2
* Body weight \< 40 kg

Primary outcomes:
measure: Rate of asthma exacerbations during the 52-week placebo-controlled period
timeFrame: weeks 0-52
Secondary outcomes:
measure: Change in lung function: pre-bronchodilator FEV1
timeFrame: from baseline to week 52
measure: Time to first asthma exacerbation
timeFrame: from baseline to week 52
measure: Change in fractional exhaled nitric oxide (FeNO)
timeFrame: from baseline to week 52
measure: Change in asthma-specific health-related quality of life, assessed by the Standardized Asthma Quality of Life Questionnaire (AQLQ[S])
timeFrame: from baseline to week 52
measure: Change in asthma rescue medication use
timeFrame: from baseline to week 52
measure: Rate of urgent asthma-related health care utilization during the 52-week placebo-controlled period
timeFrame: from baseline to week 52
Other outcomes:
Locations:
city: Pell City
country: United States
state: Alabama
city: Scottsdale
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Bakersfield
country: United States
state: California
city: Fountain Valley
country: United States
state: California
city: Fullerton
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Mission Viejo
country: United States
state: California
city: Napa
country: United States
state: California
city: Orange
country: United States
state: California
city: Rancho Mirage
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: Studio City
country: United States
state: California
city: Upland
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Centennial
country: United States
state: Colorado
city: Colorado Springs
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Wheat Ridge
country: United States
state: Colorado
city: Waterbury
country: United States
state: Connecticut
city: Gainesville
country: United States
state: Florida
city: North Palm Beach
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Tallahassee
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Albany
country: United States
state: Georgia
city: Savannah
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: River Forest
country: United States
state: Illinois
city: Topeka
country: United States
state: Kansas
city: Metairie
country: United States
state: Louisiana
city: Bangor
country: United States
state: Maine
city: Kansas City
country: United States
state: Missouri
city: Bellevue
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: Las Vegas
country: United States
state: Nevada
city: Albuquerque
country: United States
state: New Mexico
city: Bronx
country: United States
state: New York
city: Great Neck
country: United States
state: New York
city: New York
country: United States
state: New York
city: Rockville Centre
country: United States
state: New York
city: High Point
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Eugene
country: United States
state: Oregon
city: Lake Oswego
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Blue Bell
country: United States
state: Pennsylvania
city: Easton
country: United States
state: Pennsylvania
city: Harrisburg
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Upland
country: United States
state: Pennsylvania
city: Warwick
country: United States
state: Rhode Island
city: Greenville
country: United States
state: South Carolina
city: Spartanburg
country: United States
state: South Carolina
city: Knoxville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: El Paso
country: United States
state: Texas
city: Fort worth
country: United States
state: Texas
city: McKinney
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Henrico
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Nedlands
country: Australia
state: Western Australia
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Chen M, Shepard K 2nd, Yang M, Raut P, Pazwash H, Holweg CTJ, Choo E. Overlap of allergic, eosinophilic and type 2 inflammatory subtypes in moderate-to-severe asthma. Clin Exp Allergy. 2021 Apr;51(4):546-555. doi: 10.1111/cea.13790. Epub 2021 Jan 7.
citation: Hanania NA, Noonan M, Corren J, Korenblat P, Zheng Y, Fischer SK, Cheu M, Putnam WS, Murray E, Scheerens H, Holweg CT, Maciuca R, Gray S, Doyle R, McClintock D, Olsson J, Matthews JG, Yen K. Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies. Thorax. 2015 Aug;70(8):748-56. doi: 10.1136/thoraxjnl-2014-206719. Epub 2015 May 22.