A Study to Evaluate Safety and Efficacy of Lebrikizumab in Participants With Chronic Obstructive Pulmonary Disease (COPD)

A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Lebrikizumab in Patients With Chronic Obstructive Pulmonary Disease and a History of Exacerbations

Phase II, randomized, double-blind, placebo-controlled, parallel-group clinical trial of lebrikizumab in participants with COPD and a history of exacerbations who are treated with inhaled corticosteroid (ICS) and at least one long-acting bronchodilator inhaler medication. This study will be conducted to assess the safety, efficacy, and patient-reported outcome (PRO) measures.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Lebrikizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 309
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426ABP
    • Centro Médico Dra de Salvo
  • Mar Del Plata, Argentina, CP 7600
    • Instituto Ave Pulmo
  • Quilmes, Argentina, 1878
    • Centro Respiratorio Quilmes
  • San Miguel de Tucuman, Argentina, 4000
    • Investigaciones en Patologias Respiratorias
  • Santa Fe, Argentina, 3000
    • Instituto Del Buen Aire
• Bulgaria
  • Ruse, Bulgaria, 7002
    • Specialized Hospital For Active Treatment of Pneumophthisiatric Diseases; Dept of Pneumonology
  • Sofia, Bulgaria, 1233
    • Fifth MHAT - Sofia EAD
  • Sofia, Bulgaria, 1202
    • MHC - Sofia, EOOD
  • Sofia, Bulgaria, 2233
    • National Multiprofile Transport Hospital Tzar Boris Ill; Clinic of Internal Diseases
  • Stara Zagora, Bulgaria, 6000
    • Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
  • Veliko Tarnovo, Bulgaria, 5000
    • Medical Center Tara OOD
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2K 3S8
      • Concordia Hospital,Repiratory Research
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Centre
    • Toronto, Ontario, Canada, M5T 3A9
      • Inspiration Research Limited
• Denmark
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital, Lungemedicinsk Afdeling
  • København NV, Denmark, 2400
    • Lungemedicinsk afd. L, Bispebjerg Hospital
  • Odense C, Denmark, 5000
    • Odense Universitetshospital, Lungemedicinsk Forskningsenhed
• Hungary
  • Balassagyarmat, Hungary, 2660
    • Dr. Kenessey Albert Korhaz Es Rendelointezet; Tudoosztaly (Pulmonolgy Dept )
  • Gyor, Hungary, 9024
    • Petz Aladár Megyei Oktató Kórház
  • Komárom, Hungary, 2900
    • Selye János Kórház és Rendelőintézet; Allergológiai Szakrendelés
  • Miskolc, Hungary, 3529
    • CRU Hungary Kft
  • Mohacs, Hungary, 7700
    • Mohacsi Korhaz
  • Mátraháza, Hungary, 3233
    • Matrai Állami Gyógyintézet ; Bronchológia
  • Szombathely, Hungary, 9700
    • Markusovszky Egyetemi Oktatokorhaz; Tudogondozo
  • Százhalombatta, Hungary, 2440
    • Farmakontroll Bt.
• Mexico
  • Durango, Mexico, 34080
    • Centro de Investigacion y Atencion Integral Durango CIAID
  • Guadalajara, Mexico, 44100
    • Instituto Jalisciense de Investigacion Clinica S.A. de C.V.
  • Mexico, Mexico, 14050
    • Centro Respiratorio de Mexico
  • Oaxaca, Mexico, 68000
    • Oaxaca Site Management Organization
  • Querétaro, Mexico, 76800
    • Centro Integral Médico SJR SC
• Poland
  • Grodzisk Mazowiecki, Poland, 05-825
    • Mazowieckie Centrum Badań Klinicznych s.c.
  • Lublin, Poland, 02-090
    • MS Clinsearch Specjalistyczny NZOZ Janusz Milanowski Katarzyna Szmygin-Milanowska Spółka Jawna
  • Lódz, Poland, 90-153
    • Poradnia Pulmonologiczna dla Doroslych
  • Ruda Śląska, Poland, 41-707
    • Niepubliczny Zaklad Opieki Zdrowotnej PROFILAKTYKA Wladyslaw Pierzchala
  • Wroclaw, Poland, 54-239
    • NZOZ Lekarze Specjalisci
• Russian Federation
  • Moscow, Russian Federation, 105077
    • FSI Scientific Research Inst
  • Moscow, Russian Federation, 125367
    • Central Clinical Hospital #1 of RZhD JCS
  • Novosibirsk, Russian Federation, 630099
    • LLC Reafan
  • Novosibirsk, Russian Federation, 630008
    • Novosibirsk Municipal Clinical Hospital For Emergency Medicine #2
  • Novosibirsk, Russian Federation, 630087
    • State Novosibirsk Regional Clinical Hospital
  • Saint Petersburg, Russian Federation, 190068
    • LLC Medical Center "Alliance-Biomedical - Russian Group"
  • St Petersburg, Russian Federation, 197089
    • SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF
  • St. Petersburg, Russian Federation, 197089
    • St. Petersburg State Medical University n.a. I.P. Pavlov
  • Tomsk, Russian Federation, 634050
    • Siberian State Medical University
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Phoenix Medical Research Institute, LLC; Phoenix Medical Research Institute, LLC
  • California
    • Northridge, California, United States, 91324
      • California Medical Research Associates, Inc.
    • Palm Springs, California, United States, 92262
      • Palmtree Clinical Research Inc
  • Florida
    • Miami, Florida, United States, 33126
      • Finlay Medical Research
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Columbus Regional Research Institute
    • Savannah, Georgia, United States, 31405
      • Southeast Regional Res Group
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Centex Studies
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • The Clinical Research Ctr
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Comprehensive Clinical Research Inc.
  • New York
    • Jamaica, New York, United States, 11435
      • ISA Clinical Research
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Gastonia Pharmaceutical Research
  • Oregon
    • Medford, Oregon, United States, 97504
      • Clinical Research Inst. of Southern Oregon, PC
  • South Carolina
    • Indian Land, South Carolina, United States, 29707
      • Piedmont Research Partners LLC
    • Spartanburg, South Carolina, United States, 29303
      • S. Carolina Pharmaceutical Research
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine; Ben Taub Hospital- Guntupalli
    • Houston, Texas, United States, 77062
      • Centex Studies
  • Washington
    • Everett, Washington, United States, 98208
      • Western Washington Medical Group
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research
    • Tacoma, Washington, United States, 98405
      • MultiCare Health Center of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented history of COPD greater than or equal to (>/=) 12 months prior to Visit 1
• Post-bronchodilator FEV1/FVC less than (<) 0.70 at Visit 1 or 2
• Post bronchodilator FEV1 <80% predicted at Visit 1 or 2
• Documented history of one or more acute COPD exacerbations requiring treatment with systemic corticosteroids and/or antibiotics or hospitalization within 12 months prior to Visit 1
• Current tobacco smoker or former smoker (having stopped smoking for at least 6 months prior to Visit 1) with a history of smoking >/=10 pack-years (20 cigarettes/day for 10 years)
• On inhaled corticosteroids (ICS) therapy for >/=6 months prior to Visit 1
• On an eligible bronchodilator medication for >/=6 months prior to Visit 1
• Chest X-ray or computed tomography (CT) scan within 6 months prior to Visit 1 or chest X-ray prior to Visit 2 that confirms absence of clinically significant lung disease besides COPD
• Demonstrated adherence with background COPD inhaler medication during screening period
• For female participants of childbearing age, use of single or combined contraceptive methods for the duration of the study

Exclusion Criteria:

• History of severe allergic reaction or anaphylactic reaction to biologic agent or known hypersensitivity to lebrikizumab injection
• History of clinically significant pulmonary disease other than COPD
• Diagnosis of alpha-1-antitrypsin deficiency
• Lung volume reduction surgery or procedure within 12 months prior to Visit 1
• Supplemental oxygen requirement >2 liters/minute (L/min) at rest or with exertion
• Current diagnosis of asthma
• Participants participating in, or scheduled for, an intensive COPD rehabilitation program
• Maintenance oral corticosteroid therapy
• Treatment with systemic corticosteroids within 4 weeks prior to Visit 1 or during screen period
• Unstable ischemic heart disease or other relevant cardiovascular disorders
• Use of an immunomodulatory or immunosuppressive therapy including monoclonal antibodies (includes anti-interleukin-13 (IL) or anti-IL-4/IL-13 therapy)
• Body weight <40 kg
• Any infection that resulted in hospital admission for >/= 24 hours and/or treatment with oral, intravenous (IV), or intramuscular (IM) antibiotics within 4 weeks prior to Visit 1 or during screening
• Upper or lower respiratory tract infection within 4 weeks prior to Visit 1 or during screening
• Active parasitic or Listeria monocytogenes infection within 6 months prior to Visit 1 or during screening
• Received a live attenuated vaccine within 4 weeks prior to Visit 1 or during screening
• Active tuberculosis requiring treatment within 12 months prior to Visit 1
• Human immunodeficiency virus (HIV) or other known immunodeficiency
• Hepatitis or known liver cirrhosis
• Aspartate Aminotransferase (AST), Alanine Aminotransferase (ATL), or total bilirubin elevation >/=2.0 x upper limit of normal (ULN) during screening
• Clinically significant abnormality on screening electrocardiogram (ECG) or laboratory tests
• History of alcohol or drug abuse
• Pregnant or lactating

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lebrikizumab: Biomarker-high; Lebrikizumab will be administered subcutaneously once in every 4 weeks up to 24 weeks to the participants considered as biomarker-high.	Drug: Lebrikizumab; Lebrikizumab 125 milligrams (mg) will be administered subcutaneously once in every 4 weeks.
Experimental: Lebrikizumab: Biomarker-low; Lebrikizumab will be administered subcutaneously once in every 4 weeks up to 24 weeks to the participants considered as biomarker-low.	Drug: Lebrikizumab; Lebrikizumab 125 milligrams (mg) will be administered subcutaneously once in every 4 weeks.
Placebo Comparator: Placebo: Biomarker-high; Matching placebo will be administered subcutaneously once in every 4 weeks up to 24 weeks to the participants considered as biomarker-high.	Drug: Placebo; Matching placebo will be administered subcutaneously once in every 4 weeks.
Placebo Comparator: Placebo: Biomarker-low; Matching placebo will be administered subcutaneously once in every 4 weeks up to 24 weeks to the participants considered as biomarker-low.	Drug: Placebo; Matching placebo will be administered subcutaneously once in every 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute Change From Baseline in Pre-bronchodilator Forced Expiratory Volume (FEV1) at Week 12	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of Moderate or Severe COPD Exacerbation	Baseline up to Week 24
Absolute Change From Baseline in Post-bronchodilator FEV1 at Week 24	Baseline, Week 24
Absolute Change From Baseline in Pre-bronchodilator FEV1 at Week 24	Baseline, Week 24
Time to First COPD Exacerbation	Baseline up to Week 24
Change From Baseline in Health-related Quality of Life as Assessed by the Overall Score of the Saint George's Respiratory Questionnaire for COPD (SGRQ-C) at Week 24	Baseline, Week 24
Change From Baseline in COPD Symptoms as Measured by the Overall Score of the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) at Week 24	Baseline, Week 24
Change From Baseline in Cough and Sputum as Measured by the Cough and Sputum Domain Score of the EXACT at Week 24	Baseline, Week 24
Change From Baseline in Dyspnea as Assessed by the Baseline Dyspnea Index/Transition Dyspnea Index (BDI/TDI) at Week 24	Baseline, Week 24
Percentage of Participants with Adverse Events And Serious Adverse Events	Baseline up to Week 36
Percentage of Participants with Anti-therapeutic Antibody (ATA) to Lebrikizumab	Baseline up to Week 36
Minimum Observed Serum Trough Lebrikizumab Concentration (Cmin)	Pre-dose (Hour 0) at Weeks 4 and 12, at Week 24
Plasma Decay Half-Life (t1/2)	Pre-dose (Hour 0) on Day 1 (Baseline) and Weeks 1, 4, 8, 12, 16, 20; at Weeks 24, 28, and 36

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2015
• Primary Completion (Actual): November 25, 2016
• Study Completion (Actual): November 25, 2016

Study Registration Dates

• First Submitted: September 9, 2015
• First Submitted That Met QC Criteria: September 9, 2015
• First Posted (Estimate): September 11, 2015

Study Record Updates

• Last Update Posted (Actual): September 6, 2017
• Last Update Submitted That Met QC Criteria: September 5, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: WB29804; 2015-001122-42 (EudraCT Number)