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: Drug: Lebrikizumab; Other: Placebo; Drug: Montelukast

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

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90020-090
      • Santa Casa de Misericordia de Porto Alegre
  • Santa Catarina
    • Florianópolis, Santa Catarina, Brazil, 88040-970
      • Ufsc - Nupaiva
  • São Paulo
    • Santo André, São Paulo, Brazil, 09080-000
      • Pesquisare Saúde Sociedade Simples
    • Santo André, São Paulo, Brazil, 09060-650
      • Faculdade de Medicina do ABC - FMABC; Oncologia e Hematologia
• Bulgaria
  • Gabrovo, Bulgaria, 5300
    • SHATPD ? Gabrovo EOOD; Department of pneumology
  • Razgrad, Bulgaria, 7200
    • MHAT "Sv. Ivan Rilski" ? Razgrad AD; Department of pnemology and phthisiatry
  • Rousse, Bulgaria, 7002
    • SHATPPD Dr. Dimitar Gramatikov, Ruse Ltd.
  • Sofia, Bulgaria, 1000
    • Medical Center Excelsior OOD
  • Varna, Bulgaria, 9000
    • Medical Center Researchexpert OOD
  • Veliko Tarnovo, Bulgaria, 5000
    • Medical Center Tara OOD
• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Aggarwal and Associates
    • Toronto, Ontario, Canada, M9V 4B4
      • Dr. Anil K. Gupta Medicine Professional Corporation
• Czechia
  • Jind?ich?v Hradec, Czechia, 377 01
    • MediTrial s.r.o.
  • Karlovy Vary ? Stará Role, Czechia, 360 17
    • Pneumo - KV; Ordinace pneumologie a diagnostiky plicních funkcí
  • Strakonice, Czechia, 38601
    • Ordinace pro tuberkulozu a respiracni nemoci
• New Zealand
  • Auckland, New Zealand, 1010
    • Optimal Clinical Trials
  • Beckenham, New Zealand, 8024
    • Southern Clinical Trials, Ltd
• Poland
  • Bialystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczny w Bialymstoku Klinika Alergologii i Chorob Wewnetrznych
  • Krakow, Poland, 31-023
    • Grazyna Pulka Specjalistyczny Osrodek ALL-MED
  • Krakow, Poland, 31-159
    • GRA?YNA JASIENIAK-PINIS ATOPIA Niepubliczny Zak?ad Opieki Zdrowotnej Poradnie Specjalistyczne
  • Poznan, Poland, 60-693
    • Specjalistyczny Niepubliczny Zespol Opieki Zdrowotnej; Alergologia Plus Osrodek Diagnostyki.
  • Poznan, Poland, 60-823
    • NZOZ Alergo-Med. Specjalistyczna Przychodnia Lekarska; Poradnia Alergologiczna
  • Tarnów, Poland, 33-100
    • ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. z o. o
  • Wroclaw, Poland, 53-201
    • NZOZ ALL-MED Specjalistyczna Opieka Medyczna
• Romania
  • Bucharest, Romania, 030303
    • Compartiment Pneumologie; Fundatia Dr. Victor Babes
  • Craiova, Romania, 200446
    • Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes; Sectia Pneumologie II
  • Iași, Romania, 700115
    • Spitalul Clinic de Pneumoftiziologie Iasi; Sectia Clinica I Pneumoftiziologie
  • Oradea, Romania, 410176
    • Spitalul Clinic Municipal Dr. Gavril Curteanu Oradea; Sectia Pneumologie I
• Russia
  • Saint Petersburg, Russia, 190068
    • LLC Medical Center "Alliance-Biomedical - Russian Group"
  • Saint Petersburg, Russia, 194295
    • LLC Medical Center"REAVITA"
  • Saint Petersburg, Russia, 194354
    • Multiple-discipline City Hospital #2
  • Saratov, Russia, 410053
    • Regional Clinical Hospital
  • Yekaterinburg, Russia, 620109
    • Ural State Medical University; Pulmonology
  • Ryazan Oblast
    • Ryazan, Ryazan Oblast, Russia, 390026
      • Ryazan State Medical University named after I.P.Pavlov
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia, 197706
      • City Hospital #40 of Resort Administrative District
    • Saint Petersburg, Sankt-Peterburg, Russia, 197022
      • SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF
    • Saint Petersburg, Sankt-Peterburg, Russia, 197089
      • St. Petersburg State Medical University n.a. I.P. Pavlov
• South Africa
  • Cape Town, South Africa, 7700
    • University of Cape Town Lung Institute; Lung Clinical Research
  • Cape Town, South Africa, 7530
    • Tiervalei Trial Centre
  • Johannesburg, South Africa, 2113
    • Newtown Clinical Research
  • Lyttleton, South Africa, 0157
    • I Engelbrecht Research
  • Pretoria Gauteng Province, South Africa, 0087
    • Syzygy Clinical Research; ?Unit 3 to 7
  • Soweto, South Africa, 1818
    • Soweto Clinical Trial Centre
• United Kingdom
  • Manchester, United Kingdom, M23 9QZ
    • The Medicines Evaluation Unit
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Clinical Research Center of Alabama, LLC
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Allergy & Asthma Immunology Associates
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Los Angeles, California, United States, 90025
      • CA Allergy & Asthma Med Grp; Medical Group, Inc.
    • Los Angeles, California, United States, 90048
      • Southern California Institute For Respiratory
    • Napa, California, United States, 94558
      • North Bay Clinical Trials
    • Rancho Mirage, California, United States, 92270
      • Advances in Medicine
    • Redwood City, California, United States, 94063
      • Allergy & Asthma Consultants
    • Riverside, California, United States, 92506
      • Integrated Research Group Inc
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Storms Clinical Research; Institute
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Florida
    • Winter Park, Florida, United States, 32789
      • Florida Pulmonary Research Institute, LLC
  • Georgia
    • Duluth, Georgia, United States, 30096
      • In-Quest Medical Research, LLC
  • Illinois
    • Normal, Illinois, United States, 61761
      • Sneeze, Wheeze, & Itch Associates
    • River Forest, Illinois, United States, 60305
      • Asthma & Allergy Center of Chicago, S.C.
  • Kentucky
    • Louisville, Kentucky, United States, 40223
      • Family Allergy & Asthma
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Midwest Clinical Research LLC
    • St Louis, Missouri, United States, 63141
      • The Clinical Research Ctr
  • Nebraska
    • Papillion, Nebraska, United States, 68046
      • Asthma & Allergy Center, P.C.
  • Nevada
    • Reno, Nevada, United States, 89511
      • Advanced Research Institute
  • New Jersey
    • Ocean City, New Jersey, United States, 07712
      • Atlantic Research Center, LLC
  • New York
    • The Bronx, New York, United States, 10459
      • Urban Health Plan, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Allergy, Asthma & Clinical Research Center
  • Oregon
    • Medford, Oregon, United States, 97504
      • Clinical Research Inst. of Southern Oregon, Pc
    • Portland, Oregon, United States, 97202
      • Allergy Associates Research Center LLC - CRN
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Mountainview Clinical Research
  • Texas
    • Boerne, Texas, United States, 78006
      • TTS Research
    • Dallas, Texas, United States, 75231
      • Pharmaceutical Research & Consulting, Inc.
    • Dallas, Texas, United States, 75231
      • Allergy Asthma Research Assoc
    • Houston, Texas, United States, 77034
      • Texas Institute of chest and Sleep Disorder
    • McKinney, Texas, United States, 75069
      • Metroplex Pulmonology & Sleep Center
    • San Antonio, Texas, United States, 78249
      • Bandera Family Health Care
    • San Antonio, Texas, United States, 78207
      • Quality Assurance Research Center
    • San Antonio, Texas, United States, 78251
      • South Texas Allergy and Asthma Medical Professionals
    • Waco, Texas, United States, 76712
      • Allergy & Asthma Center
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • O & O Alpan, LLC
    • Richmond, Virginia, United States, 23220
      • Clinical Research Partners, LLC
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Allergy Asthma & Sinus Center

Participation Criteria

Eligibility Criteria

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

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; Lebrikizumab-matched placebo SC injection given on Days 1, 29, and 57
Active Comparator: Montelukast	Drug: Montelukast; 10 mg tablet given orally once daily for 12 weeks, according to the approved label.; Other Names: Singulair
Experimental: Lebrikizumab	Drug: Lebrikizumab; Lebrikizumab 125 mg subcutaneous (SC) injection given on Days 1, 29, and 57; Other Names: RO5490255

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 12	FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. The active comparator treatment arm of open-label montelukast was included in the study design so that the sensitivity of the study could be evaluated with respect to the primary outcome measure, FEV1. Two mixed-effect models of repeated measures (MMRM) were used to estimate the absolute change from baseline values: one for the lebrikizumab vs. placebo primary comparison and the second for the montelukast vs. placebo sensitivity comparison.	Baseline through Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lebrikizumab vs. Placebo: Change From Baseline in Asthma Reliever Medication Use at Week 12	Participants could only receive SABA therapy for asthma treatment as asthma reliever medication (<10 puffs daily). SABA use was recorded in the eDiary. A mixed-effect model of repeated measures (MMRM) was used to estimate the absolute change from baseline values for the comparison between the double-blind lebrikizumab and placebo study arms.	Baseline through Week 12
Lebrikizumab vs. Placebo: Change From Baseline in the Standardized Asthma Quality of Life Questionnaire (AQLQ[S]) Overall Score at Week 12	The AQLQ[S] was used to assess the participant's asthma-specific health-related quality of life. The 32-item questionnaire contains four domains: activity limitations, symptoms, emotional function, and environmental stimuli. The AQLQ[S] has a recall specification of 2 weeks. Participants were asked to think about how they had been during the previous 2 weeks and to respond to each of the 32 questions on a 7-point scale (7 = not impaired at all; 1 = severely impaired). An increase in the AQLQ score indicates a better quality of life. The overall AQLQ score is the mean of all 32 responses and the individual domain scores are the means of the items in those domains. A mixed-effect model of repeated measures (MMRM) was used to estimate the change from baseline values.	Baseline through Week 12
Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Levels at Week 12		Baseline, Week 12
Montelukast vs. Placebo: Change Fom Baseline in Morning Pre-bronchodilator Peak Expiratory Flow (PEF) at Week 12	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. The active comparator treatment arm of open-label montelukast was included in the study design so that the sensitivity of the study could be evaluated with respect to this secondary outcome measure of PEF. A mixed-effect model of repeated measures (MMRM) was used to estimate the absolute change from baseline values for the sensitivity comparison between montelukast (open-label, active comparator) and placebo study arms.	Baseline through Week 12
Lebrikizumab vs. Placebo: Change From Baseline in Morning Pre-bronchodilator PEF at Week 12	Peak expiratory flow (PEF) is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. A mixed-effect model of repeated measures (MMRM) was used to estimate the absolute change from baseline values for the comparison between the double-blind lebrikizumab and placebo study arms.	Baseline through Week 12
Lebrikizumab vs. Placebo: Number of Participants With Treatment Failure	Treatment failure was defined as a worsening of asthma symptoms (per investigator's assessment of participant report) in association with either relative decline in pre-bronchodilator FEV1 >=20%; or >=20% decline in morning pre-bronchodilator PEF on 2 consecutive days compared with baseline; or use of >=10 puffs of albuterol metered dose inhaler (MDI); or >=2 additional administrations (or any new use) of nebulized short-acting β-agonist (SABA) therapy within any calendar day; or need for any inhaled, oral, or parenteral corticosteroid or for a controller medication. The hazard ratio from the Cox Proportional Hazards model compared the risk of treatment failure for the lebrikizumab-treated and placebo participants.	Baseline up to Week 12
Lebrikizumab vs. Placebo: Time to Treatment Failure	Treatment failure was defined as a worsening of asthma symptoms (per investigator's assessment of participant report) in association with either relative decline in pre-bronchodilator FEV1 >=20%; or >=20% decline in morning pre-bronchodilator PEF on 2 consecutive days compared with baseline; or use of >=10 puffs of albuterol metered dose inhaler (MDI); or >=2 additional administrations (or any new use) of nebulized short-acting β-agonist (SABA) therapy within any calendar day; or need for any inhaled, oral, or parenteral corticosteroid or for a controller medication. Time to treatment failure was estimated using Kaplan-Meier method.	Basleine up to Week 12
Change From Baseline in Blood Eosinophil Count at Week 12		Baseline, Week 12
Change From Baseline in Serum Periostin at Week 12		Baseline, Week 12
Change From Baseline in Total Immunoglobulin E (IgE) Levels at Week 12		Baseline, Week 12
Change From Baseline in C-C Motif Chemokine Ligand 13 (CCL-13) Levels at Week 12		Baseline, Week 12
Change From Baseline in CCL-17 Levels at Week 12		Baseline, Week 12
Maximum Serum Lebrikizumab Concentration (Cmax) After the First Dose	According to the protocol and statistical analysis plan, a single PK sample was collected per participant after the first dose at the expected time of the maximum serum lebrikizumab concentration.	Predose on Day 0 and post-Day 1 dose on Day 7
Time to Reach Maximum Lebrikizumab Concentration After the First Dose (Tmax)	According to the protocol and statistical analysis plan, the Tmax, Week1 (first dose) value was estimated on the basis of a single pharmacokinetic (PK) timepoint per participant after the first dose, which was taken at the expected time of the maximum serum lebrikizumab concentration.	Post-Day 1 dose on Day 7
Elimination Half-Life (t1/2) of Lebrikizumab	According to the protocol and statistical analysis plan, the t1/2 was estimated based on the seven total PK samples collected per participant.	Predose on Days 0, 28, and 56, and on Days 7, 84, 112, and 140
Predose Serum Lebrikizumab Concentration (Cmin) at Week 4		Predose on Day 28 (Week 4)
Serum Lebrikizumab Concentration at Week 12		On Day 84 (Week 12)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, 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 (Actual): June 7, 2014
• Primary Completion (Actual): January 22, 2016
• Study Completion (Actual): January 22, 2016

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Actual): July 17, 2026
• Last Update Submitted That Met QC Criteria: June 19, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; 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; lebrikizumab; montelukast
• Other Study ID Numbers: WA29249; 2013-004625-81 (EudraCT Number)