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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01987492
Collaborator
(none)
230
Enrollment
71
Locations
3
Arms
33.7
Actual Duration (Months)
3.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
230 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Feb 28, 2014
Actual Primary Completion Date :
Dec 20, 2016
Actual Study Completion Date :
Dec 20, 2016

Arms and Interventions

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.

Drug: Lebrikizumab
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.

    Drug: Lebrikizumab
    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.

    Drug: Lebrikizumab
    Lebrikizumab will be administered as SC injections every 4 weeks at dose and schedule described in arm description.
    Other Names:
  • RO5490255

    • Drug: Placebo
    Placebo matching to lebrikizumab will be administered as SC injections every 4 weeks as per schedule described in arm description.

    Outcome Measures

    Primary Outcome Measures

    1. Relative Change From Baseline in Daily OCS Dose at Week 44 [Baseline, Week 44]

    Secondary Outcome Measures

    1. Absolute Change From Baseline in Daily OCS Dose at Week 44 [Baseline, Week 44]

    2. Relative Change From Week 12 in Average OCS Dose at Week 44 [Week 12, Week 44]

    3. Percentage of Participants Achieving at Least a 50 percent (%) Reduction in Their Daily OCS Dose at Week 44 Relative to Baseline [Baseline, Week 44]

    4. 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.

    5. 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.

    6. Percentage of Participants With Adverse Events [Baseline up to 24 weeks after last dose administration (up to a minimum of approximately 2 years)]

    7. 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)]

    8. Minimum Observed Serum Lebrikizumab Concentration (Cmin) [Predose (0 hours) at Weeks 4, 12, 24, 36, and 44]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT01987492
    Other Study ID Numbers:
    • WB28182
    • 2012-000190-24
    First Posted:
    Nov 19, 2013
    Last Update Posted:
    May 22, 2017
    Last Verified:
    May 1, 2017
    Additional relevant MeSH terms:
    Asthma

    Study Results

    No Results Posted as of May 22, 2017