Clinical trial NCT02104674: A Study Evaluating the Efficacy and Safety of Lebrikizumab in Adult Patients With Mild to Moderate Asthma
Official title: A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF LEBRIKIZUMAB IN ADULT PATIENTS WITH MILD TO MODERATE ASTHMA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-04-04
Enrollment: 313
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 Phase III, randomized, double-blind, placebo-controlled, multicenter study will assess the efficacy and safety of lebrikizumab in adult patients with mild to moderate asthma treated with short-acting beta-agonist (SABA) therapy alone. Patients will be randomized in a 1:1:1 ratio to receive either blinded lebrikizumab or placebo treatment by subcutaneous (SC) injection (every 4 weeks for a total of 3 doses) or open-label treatment with Singulair (Montelukast; 10 mg daily). Time on study treatment will last 12 weeks.


Eligibility criteria: Inclusion Criteria:

* Age 18-75 years old at study start
* Asthma diagnosis for \>/= 12 months prior to study start
* Bronchodilator response at screening
* Pre-bronchodilator FEV1 of 60% - 85% predicted at both screening visits 2 and 3
* No other clinically significant lung disease as confirmed by chest X-ray or computed tomography (CT) scan
* Stable and symptomatic asthma during the screening period
* Use of effective contraception, as defined by the protocol, until 24 weeks after the last dose

Exclusion Criteria:

* Maintenance of corticosteroid therapy, defined as daily or alternate-day oral corticosteroid maintenance therapy within 3 months prior to study start
* Treatment with systemic or inhaled corticosteroids within 4 weeks prior to study start or during the screening period for any reason, including an acute exacerbation event
* Treatment with a leukotriene receptor antagonist (LTRA), long-acting beta-agonist (LABA) long-acting muscarinic antagonist (LAMA), zileuton, roflumilast, or theophylline within 2 weeks prior to study start
* Documented prior treatment failure with Montelukast
* Treatment with intra-articular corticosteroids within 4 weeks prior to study start or during the screening period or anticipated need for intra articular corticosteroids during the course of the study
* Any infection requiring hospital, IV or IM antibiotic treatment or any respiratory infection within 4 weeks of study start. Any infection requiring oral antibiotic treatment within 2 weeks of study start, or any parasitic infection within 6 months of study start
* Clinically significant abnormality found during screening or clinically significant medical disease that is uncontrolled despite treatment that is likely, in the opinion of the investigator, to impact the patient's ability to participate in the study, or impact the study assessments
* History of interstitial lung disease, chronic obstructive pulmonary disease (COPD), or other clinically significant lung disease other than asthma
* History of alcohol or drug abuse that would impair or risk the patient's full participation in the study, in the opinion of the investigator
* Current or history of smoking (\> 10 pack-years), or unwillingness to abstain from smoking for the duration of the study
* Past and/or current use of any anti-IL-13 or anti- IL4/IL-13 therapy, including lebrikizumab
* Use of a licensed or investigational monoclonal antibody other than anti IL-13 or anti-IL-4/IL-13, including, but not limited to, omalizumab, anti-IL-5, or anti IL-17, within 6 months or 5 drug half-lives prior to Visit 1 (whichever is longer) or during screening
* Use of a systemic immunomodulatory or immunosuppressive therapy within 3 months or 5 drug half-lives prior to study start or during screening
* Use of other investigational therapy within 4 weeks or 5 drug half-lives prior to study start (whichever is longer) or during screening
* Initiation of or change in allergen immunotherapy within 3 months prior to study start or during screening
* Receipt of a live attenuated vaccine within 4 weeks prior to study start of during screening
* Pregnancy or breast feeding
* Body mass index \> 38 kg/m2
* Body weight \< 40 kg
* History of bronchial thermoplasty

Primary outcomes:
measure: Absolute change in pre-bronchodilator forced expiratory volume in 1 second (FEV1)
timeFrame: From Baseline to Week 12
Secondary outcomes:
measure: Relative change in morning pre-bronchodilator peak expiratory flow (PEF)
timeFrame: From Baseline to Week 12
measure: Time to treatment failure
timeFrame: From Baseline to Week 12
measure: Change in asthma rescue medication use
timeFrame: From Baseline to Week 12
measure: Incidence of adverse events
timeFrame: Approximately 20 weeks
measure: Pharmacodynamics: Relative change in fractional exhaled nitric oxide (FeNO)
timeFrame: From Baseline to Week 12
measure: Pharmacodynamics: Change in blood eosinophil count
timeFrame: From Baseline to Week 12
measure: Pharmacokinetics: Maximum serum lebrikizumab concentration after the first dose (Cmax)
timeFrame: Week 1
measure: Change in patient-reported outcome, as measured by the Standardized Asthma Quality of Life Questionnaire (AQLQ(S))
timeFrame: From Baseline to Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Flagstaff
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Alhambra
country: United States
state: California
city: Anaheim
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Napa
country: United States
state: California
city: Rancho Mirage
country: United States
state: California
city: Redwood City
country: United States
state: California
city: Stockton
country: United States
state: California
city: Upland
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Waterbury
country: United States
state: Connecticut
city: Cooper City
country: United States
state: Florida
city: Kissimmee
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Columbus
country: United States
state: Georgia
city: Duluth
country: United States
state: Georgia
city: Normal
country: United States
state: Illinois
city: Oak Lawn
country: United States
state: Illinois
city: River Forest
country: United States
state: Illinois
city: Avon
country: United States
state: Indiana
city: Louisville
country: United States
state: Kentucky
city: Minneapolis
country: United States
state: Minnesota
city: Plymouth
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Papillion
country: United States
state: Nebraska
city: Ocean
country: United States
state: New Jersey
city: Bronx
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Hendersonville
country: United States
state: North Carolina
city: High Point
country: United States
state: North Carolina
city: Oklahoma City
country: United States
state: Oklahoma
city: Medford
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Greer
country: United States
state: South Carolina
city: Boerne
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Humble
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: San Antonio
country: United States
state: Texas
city: Tomball
country: United States
state: Texas
city: Waco
country: United States
state: Texas
city: Fairfax
country: United States
state: Virginia
city: Henrico
country: United States
state: Virginia
city: Greenfield
country: United States
state: Wisconsin
city: Rio de Janeiro
country: Brazil
state: RJ
city: Porto Alegre
country: Brazil
state: RS
city: Florianopolis
country: Brazil
state: SC
city: Santo Andre
country: Brazil
state: SP
city: Santo Andre
country: Brazil
state: SP
city: Gabrovo
country: Bulgaria
city: Razgrad
country: Bulgaria
city: Ruse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Veliko Tarnovo
country: Bulgaria
city: Brampton
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Jablonec nad Nisou
country: Czech Republic
city: Jindrichuv Hradec
country: Czech Republic
city: Karlovy Vary - Stará Role
country: Czech Republic
city: Strakonice
country: Czech Republic
city: Tbilisi
country: Georgia
city: Auckland City
country: New Zealand
city: Auckland
country: New Zealand
city: Beckenham
country: New Zealand
city: Bialystok
country: Poland
city: Krakow
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Poznan
country: Poland
city: Tarnow
country: Poland
city: Wroclaw
country: Poland
city: Wroclaw
country: Poland
city: Caguas
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: Bucuresti
country: Romania
city: Cluj-Napoca
country: Romania
city: Iasi
country: Romania
city: Oradea
country: Romania
city: Timisoara
country: Romania
city: Ekaterinburg
country: Russian Federation
city: Moscow
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Saratov
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Spisska Nova Ves
country: Slovakia
city: Cape Town
country: South Africa
city: Cape Town
country: South Africa
city: Cape Town
country: South Africa
city: Johannesburg
country: South Africa
city: Lyttleton
country: South Africa
city: Parow
country: South Africa
city: Pretoria Gauteng Province
country: South Africa
city: Soweto
country: South Africa
city: Manchester
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Korenblat P, Kerwin E, Leshchenko I, Yen K, Holweg CTJ, Anzures-Cabrera J, Martin C, Putnam WS, Governale L, Olsson J, Matthews JG. Efficacy and safety of lebrikizumab in adult patients with mild-to-moderate asthma not receiving inhaled corticosteroids. Respir Med. 2018 Jan;134:143-149. doi: 10.1016/j.rmed.2017.12.006. Epub 2017 Dec 13.