A Study Evaluating the Efficacy and Safety of Lebrikizumab in Adult Patients With Mild to Moderate Asthma

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Other: placebo; Drug: montelukast [Singulair]; Drug: lebrikizumab

• Study Type: Interventional
• Enrollment (Actual): 313
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 22271-100
  • RS
    • Porto Alegre, RS, Brazil, 90020-090
  • SC
    • Florianopolis, SC, Brazil, 88040-970
  • SP
    • Santo Andre, SP, Brazil, 09060-650
    • Santo Andre, SP, Brazil, 09080-000
• Bulgaria
  • Gabrovo, Bulgaria, 5300
  • Razgrad, Bulgaria, 7200
  • Ruse, Bulgaria, 7002
  • Sofia, Bulgaria, 1431
  • Sofia, Bulgaria, 1000
  • Varna, Bulgaria, 9019
  • Veliko Tarnovo, Bulgaria, 5000
• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
    • Toronto, Ontario, Canada, M9V 4B4
• Czech Republic
  • Jablonec nad Nisou, Czech Republic, 46601
  • Jindrichuv Hradec, Czech Republic, 37701
  • Karlovy Vary - Stará Role, Czech Republic, 360 17
  • Strakonice, Czech Republic, 38601
• Georgia
  • Tbilisi, Georgia, 0119
• New Zealand
  • Auckland, New Zealand, 1010
  • Auckland City, New Zealand, 0626
  • Beckenham, New Zealand, 8024
• Poland
  • Bialystok, Poland, 15-276
  • Krakow, Poland, 31-023
  • Krakow, Poland, 31-159
  • Lodz, Poland, 90-153
  • Lublin, Poland, 20-089
  • Poznan, Poland, 60-693
  • Poznan, Poland, 60-823
  • Tarnow, Poland, 33-100
  • Wroclaw, Poland, 54-239
  • Wroclaw, Poland, 53-201
• Puerto Rico
  • Caguas, Puerto Rico, 00725
  • San Juan, Puerto Rico, 00918
  • San Juan, Puerto Rico, 00909-1711
• Romania
  • Bucuresti, Romania, 030303
  • Cluj-Napoca, Romania, 400371
  • Iasi, Romania, 700115
  • Oradea, Romania, 410176
  • Timisoara, Romania, 300310
• Russian Federation
  • Ekaterinburg, Russian Federation, 620109
  • Moscow, Russian Federation, 119991
  • Ryazan, Russian Federation, 390011
  • Saint Petersburg, Russian Federation, 190068
  • Saint Petersburg, Russian Federation, 194295
  • Saratov, Russian Federation, 410053
  • St Petersburg, Russian Federation, 197089
  • St Petersburg, Russian Federation, 193231
  • St. Petersburg, Russian Federation, 194354
  • St. Petersburg, Russian Federation, 197089
  • St. Petersburg, Russian Federation, 197706
• Slovakia
  • Spisska Nova Ves, Slovakia, 052 01
• South Africa
  • Cape Town, South Africa, 7530
  • Cape Town, South Africa, 7700
  • Cape Town, South Africa, 7130
  • Johannesburg, South Africa, 2113
  • Lyttleton, South Africa, 0157
  • Parow, South Africa, 7505
  • Pretoria Gauteng Province, South Africa, 0087
  • Soweto, South Africa, 1818
• United Kingdom
  • Manchester, United Kingdom, M23 9QZ
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
  • Arizona
    • Flagstaff, Arizona, United States, 86001
    • Scottsdale, Arizona, United States, 85251
  • California
    • Alhambra, California, United States, 91801
    • Anaheim, California, United States, 92801
    • Los Angeles, California, United States, 90048
    • Los Angeles, California, United States, 90025
    • Napa, California, United States, 94558
    • Rancho Mirage, California, United States, 92270
    • Redwood City, California, United States, 94063
    • Stockton, California, United States, 95207
    • Upland, California, United States, 91786
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
    • Denver, Colorado, United States, 80206
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
  • Florida
    • Cooper City, Florida, United States, 33024
    • Kissimmee, Florida, United States, 34741
    • New Port Richey, Florida, United States, 34653
    • Winter Park, Florida, United States, 32789
  • Georgia
    • Columbus, Georgia, United States, 31904
    • Duluth, Georgia, United States, 30096
  • Illinois
    • Normal, Illinois, United States, 61761
    • Oak Lawn, Illinois, United States, 60453
    • River Forest, Illinois, United States, 60305
  • Indiana
    • Avon, Indiana, United States, 46123
  • Kentucky
    • Louisville, Kentucky, United States, 40223
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
    • Plymouth, Minnesota, United States, 55441
  • Missouri
    • Saint Louis, Missouri, United States, 63141
  • Nebraska
    • Papillion, Nebraska, United States, 68046
  • New Jersey
    • Ocean, New Jersey, United States, 07712
  • New York
    • Bronx, New York, United States, 10459
    • Rochester, New York, United States, 14618
  • North Carolina
    • Hendersonville, North Carolina, United States, 28739
    • High Point, North Carolina, United States, 27262
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
  • Oregon
    • Medford, Oregon, United States, 97504
    • Portland, Oregon, United States, 97202
  • South Carolina
    • Greer, South Carolina, United States, 29651
  • Texas
    • Boerne, Texas, United States, 78006
    • Dallas, Texas, United States, 75231
    • Houston, Texas, United States, 77034
    • Humble, Texas, United States, 77338
    • McKinney, Texas, United States, 75069
    • San Antonio, Texas, United States, 78251
    • San Antonio, Texas, United States, 78207
    • San Antonio, Texas, United States, 78249
    • Tomball, Texas, United States, 77375
    • Waco, Texas, United States, 76712
  • Virginia
    • Fairfax, Virginia, United States, 22030
    • Henrico, Virginia, United States, 23233
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: placebo; SC injection given on Days 1, 29, and 57
Active Comparator: Singulair (montelukast)	Drug: montelukast [Singulair]; 10 mg given orally once daily for 12 weeks
Experimental: lebrikizumab	Drug: lebrikizumab; Given SC on Days 1, 29, and 57

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute change in pre-bronchodilator forced expiratory volume in 1 second (FEV1)	From Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Relative change in morning pre-bronchodilator peak expiratory flow (PEF)	From Baseline to Week 12
Time to treatment failure	From Baseline to Week 12
Change in asthma rescue medication use	From Baseline to Week 12
Incidence of adverse events	Approximately 20 weeks
Pharmacodynamics: Relative change in fractional exhaled nitric oxide (FeNO)	From Baseline to Week 12
Pharmacodynamics: Change in blood eosinophil count	From Baseline to Week 12
Pharmacokinetics: Maximum serum lebrikizumab concentration after the first dose (Cmax)	Week 1
Change in patient-reported outcome, as measured by the Standardized Asthma Quality of Life Questionnaire (AQLQ(S))	From Baseline to Week 12

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: March 26, 2014
• First Submitted That Met QC Criteria: April 2, 2014
• First Posted (Estimate): April 4, 2014

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Montelukast
• Other Study ID Numbers: WA29249