Clinical trial NCT01545453: A Study of Lebrikizumab in Patients With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and A Second Controller Medication (VERSE)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2012-03-06
Enrollment: 205
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: Oxford
country: United States
state: Alabama
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Orange
country: United States
state: California
city: Redwood City
country: United States
state: California
city: San Mateo
country: United States
state: California
city: Stockton
country: United States
state: California
city: Centennial
country: United States
state: Colorado
city: Colorado Springs
country: United States
state: Colorado
city: Kissimmee
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Panama City
country: United States
state: Florida
city: Columbus
country: United States
state: Georgia
city: Decatur
country: United States
state: Georgia
city: Woodstock
country: United States
state: Georgia
city: Twin Falls
country: United States
state: Idaho
city: Normal
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Lafayette
country: United States
state: Indiana
city: Overland Park
country: United States
state: Kansas
city: Baltimore
country: United States
state: Maryland
city: Brockton
country: United States
state: Massachusetts
city: Bay City
country: United States
state: Michigan
city: Novi
country: United States
state: Michigan
city: Ypsilanti
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Plymouth
country: United States
state: Minnesota
city: Chesterfield
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: St Louis
country: United States
state: Missouri
city: Missoula
country: United States
state: Montana
city: Omaha
country: United States
state: Nebraska
city: Brick
country: United States
state: New Jersey
city: Edison
country: United States
state: New Jersey
city: Ocean
country: United States
state: New Jersey
city: Teaneck
country: United States
state: New Jersey
city: Verona
country: United States
state: New Jersey
city: North Syracuse
country: United States
state: New York
city: Canton
country: United States
state: Ohio
city: Centerville
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Medford
country: United States
state: Oregon
city: Altoona
country: United States
state: Pennsylvania
city: Hershey
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Pittsburg
country: United States
state: Pennsylvania
city: Sellersville
country: United States
state: Pennsylvania
city: Columbia
country: United States
state: South Carolina
city: Greenville
country: United States
state: South Carolina
city: Austin
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Boerne
country: United States
state: Texas
city: El Paso
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Sugar Land
country: United States
state: Texas
city: Murray
country: United States
state: Utah
city: Fairfax
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Brisbane
country: Australia
state: Queensland
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.