A Study of Lebrikizumab (RO5490255) in Participants With Severe Oral Corticosteroids (OCS) Dependent Asthma
- Registration Number
- NCT01987492
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This randomized, multicenter, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy of lebrikizumab compared with placebo, as measured by the ability of participants to achieve lower daily doses of OCS, among those with severe corticosteroid-dependent asthma. Prednisone/prednisolone will be the OCS therapy prescribed. Participants will be randomized to receive lebrikizumab or matching placebo for 44 weeks in a double-blind, placebo-controlled (DBPC) period. Those who complete the 44-week period may continue into a 32-week active treatment extension (ATE) period, during which all participants will receive lebrikizumab treatment. Following completion of the ATE period, participants who have both tolerated and derived benefit from treatment with lebrikizumab may continue their lebrikizumab treatment into a long-term extension (LTE) period. Participants will transition to 24 weeks of safety follow-up upon discontinuation of study drug.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 230
- Severe asthma despite intensive follow-up by an asthma specialist for >/=6 months prior to Visit 1
- Baseline forced expiratory volume in 1 second (FEV1) >/=40% of predicted prior to randomization
- Receiving high doses of inhaled glucocorticosteroids at a total daily dose of >/=1500 micrograms (mcg) beclomethasone dipropionate or equivalent and long-acting beta-adrenoceptor agonist (LABA), with or without an additional controller, for at least 3 months prior to Visit 1
- Chronic treatment with maintenance OCS for >/=6 months prior to Visit 1
- Assessment to ensure diagnosis of refractory asthma and OCS dependence on minimal effective or maximum tolerated dose prior to Visit 1 with compliance
- History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
- Asthma exacerbation within 28 days prior to Visit 1 or during screening (prior to Visit 3)
- For adults: Active tuberculosis requiring treatment within the 12 months prior to Visit 1
- For adolescents: History of active tuberculosis requiring treatment
- Evidence of acute or chronic hepatitis or known liver cirrhosis
- Known current malignancy or current evaluation for a potential malignancy
- History of interstitial lung disease, chronic obstructive pulmonary disease, or other clinically significant lung disease other than asthma
- Infection requiring hospital admission or requiring treatment with 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 infection or Listeria monocytogenes infection within 6 months prior to Visit 1 or during screening
- Current smoker or former smoker with a smoking history of more than 15 pack-years
- Current use of an immunomodulatory/ immunosuppressive therapy or past use within 3 months or 5 drug half-lives (whichever is longer) prior to Visit 1
- Use of a licensed or investigational monoclonal antibody other than anti-interleukin (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 (whichever is longer) prior to Visit 1
- Receipt of a live attenuated vaccine within the 4 weeks prior to Visit 1 during screening or anticipation of receipt of a live attenuated vaccine throughout the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Lebrikizumab Participants will receive placebo matching to lebrikizumab SC injection every 4 weeks during the 44-week DBPC period. Participants will then be randomized to receive either high- or low-dose lebrikizumab every 4 weeks during the 32-week ATE period and will continue same treatment in the LTE period. Lebrikizumab High Dose Lebrikizumab Participants will receive lebrikizumab at high dose level as subcutaneous (SC) injection every 4 weeks during the 44-week DBPC period, followed by a 32-week ATE period, and during the LTE period. Placebo Placebo Participants will receive placebo matching to lebrikizumab SC injection every 4 weeks during the 44-week DBPC period. Participants will then be randomized to receive either high- or low-dose lebrikizumab every 4 weeks during the 32-week ATE period and will continue same treatment in the LTE period. Lebrikizumab Low Dose Lebrikizumab Participants will receive lebrikizumab at low dose level as SC injection every 4 weeks during the 44-week DBPC period, followed by a 32-week ATE period, and during the LTE period.
- Primary Outcome Measures
Name Time Method Relative Change From Baseline in Daily OCS Dose at Week 44 Baseline, Week 44
- Secondary Outcome Measures
Name Time Method Absolute Change From Baseline in Daily OCS Dose at Week 44 Baseline, Week 44 Relative Change From Week 12 in Average OCS Dose at Week 44 Week 12, Week 44 Percentage of Participants Discontinuing OCS Therapy or Having Achieved an Adrenal Maintenance Dose at Week 44 Week 44 Percentage of participants discontinuing OCS therapy or having achieved adrenal maintenance dose (cortisol level less than or equal to 100 nanomoles per liter) will be reported.
Percentage of Participants With Adverse Events Baseline up to 24 weeks after last dose administration (up to a minimum of approximately 2 years) Percentage of Participants With Anti-therapeutic Antibodies (ATAs) Against Lebrikizumab Predose (0 hours) at Weeks 0, 4, 12, 24, 36, 44, 52, 64, and 76, at early discontinuation (up to a minimum of approximately 2 years), and at 24 weeks after last dose administration (up to a minimum of approximately 2 years) Minimum Observed Serum Lebrikizumab Concentration (Cmin) Predose (0 hours) at Weeks 4, 12, 24, 36, and 44 Percentage of Participants With Asthma Exacerbations Baseline up to Week 44 An asthma exacerbation is defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, or nocturnal awakenings due to these symptoms) that lead to treatment with systemic corticosteroids greater than or equal to (\>/=) 30 milligrams (mg) or 0.5 mg per kilogram (kg) for \>/=3 consecutive days or to hospitalization.
Percentage of Participants Achieving at Least a 50 percent (%) Reduction in Their Daily OCS Dose at Week 44 Relative to Baseline Baseline, Week 44
Trial Locations
- Locations (71)
Clin Univ de Bxl Hôpital Erasme
🇧🇪Bruxelles, Belgium
Monash Medical Centre; Respiratory and Sleep Medicine
🇦🇺Clayton, Victoria, Australia
Longartsenpraktijk
🇧🇪Genk, Belgium
UZ Gent
🇧🇪Gent, Belgium
Centro Investigacion Medico Biologica y Terapia Avanzada
🇲🇽Guadalajara, Mexico
Academisch Medisch Centrum; Afdeling Longziekten, F5-258
🇳🇱Amsterdam, Netherlands
Spaarne Ziekenhuis Hoofddorp; Long Geneeskunde
🇳🇱Hoofddorp, Netherlands
Antonius Ziekenhuis; Dept of Lung Diseases
🇳🇱Nieuwegein, Netherlands
Specjalistyczny Osrodek Alergologiczno-Internistyczny ALL-MED
🇵🇱Krakow, Poland
Malopolskie Centrum Alergologii
🇵🇱Krakow, Poland
SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
🇵🇱Lodz, Poland
Specjalistyczna Poradnia Pulmonologiczna
🇵🇱Ostrow Wielkopolski, Poland
Klinika Chorób Wewnetrznych i Alergologii MSW
🇵🇱Warszawa, Poland
Centro Integral Médico SJR SC
🇲🇽Querétaro, Mexico
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Kern Allergy Med Clinic, Inc.
🇺🇸Bakersfield, California, United States
CHU de Grenoble - Hôpital André Michallon
🇫🇷Grenoble Cedex 9, France
Allergy & Immunology
🇺🇸Tulsa, Oklahoma, United States
Gentofte Hospital, Klinik for Allergi
🇩🇰Hellerup, Denmark
CHU Nantes - Hôpital Laennec; Service de Pneumologie
🇫🇷Nantes, France
Clinical Trials Unit, Bay of Plenty District Health Board
🇳🇿Tauranga, New Zealand
Inspiration Research Limited
🇨🇦Toronto, Ontario, Canada
Metroplex Pulmonology & Sleep Center
🇺🇸McKinney, Texas, United States
Hôpital de La Croix Rousse
🇫🇷Lyon, France
CH de Bicetre; Pneumologie
🇫🇷Le Kremlin Bicetre, France
Hornmed
🇨🇿Brno, Czechia
Medical Research Inst. of New Zealand; Respiratory
🇳🇿Wellington, New Zealand
Nemocnice Liberec; KNL a.s. - TRN
🇨🇿Liberec 1, Czechia
Georgia Pollens
🇺🇸Albany, Georgia, United States
Princess Alexandra Hospital, Department of Respiratory and Sleep Medicine
🇦🇺Brisbane, Queensland, Australia
Hôpital Arnaud de Villeneuve
🇫🇷Montpellier, France
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Belfast City Hospital; Respiratory Department
🇬🇧Belfast, United Kingdom
Hopital Bichat Claude Bernard ; Service de Pneumologie
🇫🇷Paris, France
Southampton General Hospital; Respiratory Department
🇬🇧Hampshire, United Kingdom
Heartlands Hospital; Respiratory Department
🇬🇧Birmingham, United Kingdom
NZ Respiratory & Sleep Institute
🇳🇿Auckland, New Zealand
Hospital Universitario Doctor Peset
🇪🇸Valencia, Spain
Instituto Jalisciense de Investigacion Clinica S.A. de C.V.
🇲🇽Guadalajara, Mexico
CHU de Haut Leveque
🇫🇷Pessac, France
Nemocnice Nový Jičín
🇨🇿Nový Jičín, Czechia
New Lister Buliding, Level 1; Clinical Research Facility
🇬🇧Glasgow, United Kingdom
Rokycanska nemocnice
🇨🇿Rokycany, Czechia
CHU de Nice
🇫🇷Nice Cedex 1, France
Dunedin Hospital
🇳🇿Dunedin, New Zealand
Royal Hospital For Children
🇬🇧Glasgow, United Kingdom
Hospital Clinico Universitario de Salamanca; Servicio de Neumologia
🇪🇸Salamanca, Spain
Hospital de la Santa Creu; i Sant Pau
🇪🇸Barcelona, Spain
ZAPA JJ Sro
🇸🇰Levice, Slovakia
Plucna ambulancia
🇸🇰Spisska Nova Ves, Slovakia
Gartnavel General Hospital; Respiratory Department
🇬🇧Glasgow, United Kingdom
Derriford Hospital; The Lind Research Department
🇬🇧Plymouth, United Kingdom
St Bartholomew's Hospital (Barts); Respiratory Department
🇬🇧London, United Kingdom
Wythenshawe Hospital; North West Lung Research Centre
🇬🇧Manchester, United Kingdom
Institute for Respiratory Health Inc
🇦🇺Nedlands, Western Australia, Australia
South Florida Research Center, Inc.
🇺🇸Miami, Florida, United States
Nouvel Hôpital Civil; Pôle de Pathologie Thoracique
🇫🇷Strabourg, France
Niepubliczny Zaklad Opieki Zdrowotnej PROFILAKTYKA Wladyslaw Pierzchala
🇵🇱Ruda Śląska, Poland
EMC Instytut Medyczny SA; Przychodnia przy ulicy Łowieckiej
🇵🇱Wrocław, Poland
Advanced Medical Concepts, PSC
🇵🇷Cidra, Puerto Rico
San Juan Bautista School of Medicine-Clinical Research Unit
🇵🇷Caguas, Puerto Rico
University Clinic of Pulmonary and Allergic Diseases Golnik
🇸🇮Golnik, Slovenia
Complejo Hospitalario Universitario de Santiago; Servicio de Neumología
🇪🇸Santiago de Compostela, La Coruña, Spain
Leicester Royal Infirmary NHS Trust
🇬🇧Leicester, United Kingdom
Glenfield Hospital; Respiratory -Allergy Unit
🇬🇧Leicester, United Kingdom
Royal Brompton Hospital; Respiratory Department
🇬🇧London, United Kingdom
Freeman Hospital; Respiratory Department
🇬🇧Newcastle upon Tyne, United Kingdom
Sheffield Clinical Research Facility; National Institute for Health Research
🇬🇧Sheffield, United Kingdom
Allergy & Asthma Care Center of Southern California
🇺🇸Long Beach, California, United States
Pioneer Research Solutions
🇺🇸Houston, Texas, United States
Pulmonary Consultants PLLC
🇺🇸Tacoma, Washington, United States