A Study of Lebrikizumab (RO5490255) in Participants With Severe Oral Corticosteroids (OCS) Dependent Asthma

May 19, 2017 updated by: Hoffmann-La Roche

A Phase II, Randomized, Double-Blind, Placebo Controlled, Multicenter Trial to Assess the Oral Corticosteroid-Sparing Effect of Lebrikizumab in Patients With Severe Corticosteroid Dependent Asthma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

230

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Queensland
      • Brisbane, Queensland, Australia, 4102
        • Princess Alexandra Hospital, Department of Respiratory and Sleep Medicine
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Medical Centre; Respiratory and Sleep Medicine
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Institute for Respiratory Health Inc
      • Bruxelles, Belgium, 1070
        • Clin Univ de Bxl Hôpital Erasme
      • Genk, Belgium, 3600
        • Longartsenpraktijk
      • Gent, Belgium, 9000
        • UZ Gent
    • Ontario
      • Toronto, Ontario, Canada, M5T 3A9
        • Inspiration Research Limited
      • Brno, Czechia, 618 00
        • Hornmed
      • Liberec 1, Czechia, 460 63
        • Nemocnice Liberec; KNL a.s. - TRN
      • Nový Jičín, Czechia, 741-01
        • Nemocnice Nový Jičín
      • Rokycany, Czechia, 337 22
        • Rokycanska nemocnice
      • Hellerup, Denmark, 2900
        • Gentofte Hospital, Klinik for Allergi
      • Grenoble Cedex 9, France, 38043
        • CHU de Grenoble - Hôpital André Michallon
      • Le Kremlin Bicetre, France, 94275
        • CH de Bicetre; Pneumologie
      • Lyon, France, 69004
        • Hopital de La Croix Rousse
      • Montpellier, France, 34295
        • Hôpital Arnaud de Villeneuve
      • Nantes, France, 44093
        • CHU Nantes - Hôpital Laennec; Service de Pneumologie
      • Nice Cedex 1, France, 06001
        • CHU de Nice
      • Paris, France, 75877
        • Hopital Bichat Claude Bernard ; Service de Pneumologie
      • Pessac, France, 33604
        • CHU de Haut Leveque
      • Strabourg, France, 67091
        • Nouvel Hôpital Civil; Pôle de Pathologie Thoracique
      • Guadalajara, Mexico, 44100
        • Instituto Jalisciense de Investigacion Clinica S.A. de C.V.
      • Guadalajara, Mexico, 44130
        • Centro Investigacion Medico Biologica y Terapia Avanzada
      • Querétaro, Mexico, 76800
        • Centro Integral Médico SJR SC
      • Amsterdam, Netherlands, 1105 AZ
        • Academisch Medisch Centrum; Afdeling Longziekten, F5-258
      • Hoofddorp, Netherlands, 2134 TM
        • Spaarne Ziekenhuis Hoofddorp; Long Geneeskunde
      • Nieuwegein, Netherlands, 3435 CM
        • Antonius Ziekenhuis; Dept of Lung Diseases
      • Auckland, New Zealand, 1051
        • NZ Respiratory & Sleep Institute
      • Dunedin, New Zealand
        • Dunedin Hospital
      • Tauranga, New Zealand, 3143
        • Clinical Trials Unit, Bay of Plenty District Health Board
      • Wellington, New Zealand
        • Medical Research Inst. of New Zealand; Respiratory
      • Krakow, Poland, 31-624
        • Malopolskie Centrum Alergologii
      • Krakow, Poland, 31-024
        • Specjalistyczny Osrodek Alergologiczno-Internistyczny ALL-MED
      • Lodz, Poland, 90-153
        • SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
      • Ostrow Wielkopolski, Poland, 63-400
        • Specjalistyczna Poradnia Pulmonologiczna
      • Ruda Śląska, Poland, 41-707
        • Niepubliczny Zaklad Opieki Zdrowotnej PROFILAKTYKA Wladyslaw Pierzchala
      • Warszawa, Poland, 02-507
        • Klinika Chorób Wewnetrznych i Alergologii MSW
      • Wrocław, Poland, 50-220
        • EMC Instytut Medyczny SA; Przychodnia przy ulicy Łowieckiej
      • Caguas, Puerto Rico, 00725
        • San Juan Bautista School of Medicine-Clinical Research Unit
      • Cidra, Puerto Rico, 00739
        • Advanced Medical Concepts, PSC
      • Levice, Slovakia, 934 01
        • ZAPA JJ Sro
      • Spisska Nova Ves, Slovakia, 052 01
        • Plucna ambulancia
      • Golnik, Slovenia, 4204
        • University Clinic of Pulmonary and Allergic Diseases Golnik
      • Barcelona, Spain, 08036
        • Hospital Clinic de Barcelona
      • Barcelona, Spain, 08025
        • Hospital de la Santa Creu; i Sant Pau
      • Salamanca, Spain, 37007
        • Hospital Clinico Universitario de Salamanca; Servicio de Neumologia
      • Valencia, Spain, 46017
        • Hospital Universitario Doctor Peset
    • La Coruña
      • Santiago de Compostela, La Coruña, Spain, 15706
        • Complejo Hospitalario Universitario de Santiago; Servicio de Neumología
      • Belfast, United Kingdom, BT9 7AB
        • Belfast City Hospital; Respiratory Department
      • Birmingham, United Kingdom, B9 5SS
        • Heartlands Hospital; Respiratory Department
      • Glasgow, United Kingdom, G51 4TF
        • Royal Hospital for Children
      • Glasgow, United Kingdom, G12 0YN
        • Gartnavel General Hospital; Respiratory Department
      • Glasgow, United Kingdom, G31 2ER
        • New Lister Buliding, Level 1; Clinical Research Facility
      • Hampshire, United Kingdom, SO16 6YD
        • Southampton General Hospital; Respiratory Department
      • Leicester, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary NHS Trust
      • Leicester, United Kingdom, LE3 9QP
        • Glenfield Hospital; Respiratory -Allergy Unit
      • London, United Kingdom, SW3 6NP
        • Royal Brompton Hospital; Respiratory Department
      • London, United Kingdom, EC1A 7BE
        • St Bartholomew's Hospital (Barts); Respiratory Department
      • Manchester, United Kingdom, M23 9LT
        • Wythenshawe Hospital; North West Lung Research Centre
      • Newcastle upon Tyne, United Kingdom, NE7 7DN
        • Freeman Hospital; Respiratory Department
      • Plymouth, United Kingdom, PL6 8DH
        • Derriford Hospital; The Lind Research Department
      • Sheffield, United Kingdom, S10 2JF
        • Sheffield Clinical Research Facility; National Institute for Health Research
    • California
      • Bakersfield, California, United States, 93301
        • Kern Allergy Med Clinic, Inc.
      • Long Beach, California, United States, 90808
        • Allergy & Asthma Care Center of Southern California
    • Florida
      • Miami, Florida, United States, 33135
        • South Florida Research Center, Inc.
    • Georgia
      • Albany, Georgia, United States, 31707
        • Georgia Pollens
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74136
        • Allergy & Immunology
    • Texas
      • Houston, Texas, United States, 77008
        • Pioneer Research Solutions
      • McKinney, Texas, United States, 75069
        • Metroplex Pulmonology & Sleep Center
    • Washington
      • Tacoma, Washington, United States, 98405
        • Pulmonary Consultants PLLC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lebrikizumab High Dose
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.
Lebrikizumab will be administered as SC injections every 4 weeks at dose and schedule described in arm description.
Other Names:
  • RO5490255
Experimental: Lebrikizumab Low Dose
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.
Lebrikizumab will be administered as SC injections every 4 weeks at dose and schedule described in arm description.
Other Names:
  • RO5490255
Placebo Comparator: 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 will be administered as SC injections every 4 weeks at dose and schedule described in arm description.
Other Names:
  • RO5490255
Placebo matching to lebrikizumab will be administered as SC injections every 4 weeks as per schedule described in arm description.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Relative Change From Baseline in Daily OCS Dose at Week 44
Time Frame: Baseline, Week 44
Baseline, Week 44

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absolute Change From Baseline in Daily OCS Dose at Week 44
Time Frame: Baseline, Week 44
Baseline, Week 44
Relative Change From Week 12 in Average OCS Dose at Week 44
Time Frame: Week 12, Week 44
Week 12, Week 44
Percentage of Participants Achieving at Least a 50 percent (%) Reduction in Their Daily OCS Dose at Week 44 Relative to Baseline
Time Frame: Baseline, Week 44
Baseline, Week 44
Percentage of Participants Discontinuing OCS Therapy or Having Achieved an Adrenal Maintenance Dose at Week 44
Time Frame: 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.
Week 44
Percentage of Participants With Asthma Exacerbations
Time Frame: 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.
Baseline up to Week 44
Percentage of Participants With Adverse Events
Time Frame: Baseline up to 24 weeks after last dose administration (up to a minimum of approximately 2 years)
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
Time Frame: 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)
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)
Time Frame: Predose (0 hours) at Weeks 4, 12, 24, 36, and 44
Predose (0 hours) at Weeks 4, 12, 24, 36, and 44

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 28, 2014

Primary Completion (Actual)

December 20, 2016

Study Completion (Actual)

December 20, 2016

Study Registration Dates

First Submitted

November 12, 2013

First Submitted That Met QC Criteria

November 12, 2013

First Posted (Estimate)

November 19, 2013

Study Record Updates

Last Update Posted (Actual)

May 22, 2017

Last Update Submitted That Met QC Criteria

May 19, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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