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

• ClinicalTrials.gov Identifier: NCT02104674
• Recruitment Status: Completed
• First Posted: April 4, 2014
• Last Update Posted: November 2, 2016
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: lebrikizumab; Drug: montelukast [Singulair]; Other: placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 313 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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 Start Date: June 2014
• Actual Primary Completion Date: May 2016
• Actual Study Completion Date: May 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Absolute change in pre-bronchodilator forced expiratory volume in 1 second (FEV1) [ Time Frame: From Baseline to Week 12 ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

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

Contacts and Locations

  Show 113 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02104674 History of Changes
• Other Study ID Numbers: WA29249
• First Posted: April 4, 2014
• Last Update Posted: November 2, 2016
• Last Verified: November 2016

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Montelukast; Antibodies, Monoclonal; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Molecular Mechanisms of Pharmacological Action; Immunologic Factors