A Study of Lebrikizumab (RO5490255) in Participants With Severe Oral Corticosteroids (OCS) Dependent Asthma
19 mai 2017 mis à jour par: 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.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
230
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Queensland
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Brisbane, Queensland, Australie, 4102
- Princess Alexandra Hospital, Department of Respiratory and Sleep Medicine
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Victoria
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Clayton, Victoria, Australie, 3168
- Monash Medical Centre; Respiratory and Sleep Medicine
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Western Australia
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Nedlands, Western Australia, Australie, 6009
- Institute for Respiratory Health Inc
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Bruxelles, Belgique, 1070
- Clin Univ de Bxl Hôpital Erasme
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Genk, Belgique, 3600
- Longartsenpraktijk
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Gent, Belgique, 9000
- UZ Gent
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Ontario
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Toronto, Ontario, Canada, M5T 3A9
- Inspiration Research Limited
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Hellerup, Danemark, 2900
- Gentofte Hospital, Klinik for Allergi
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Barcelona, Espagne, 08036
- Hospital Clinic de Barcelona
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Barcelona, Espagne, 08025
- Hospital de la Santa Creu; i Sant Pau
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Salamanca, Espagne, 37007
- Hospital Clinico Universitario de Salamanca; Servicio de Neumologia
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Valencia, Espagne, 46017
- Hospital Universitario Doctor Peset
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La Coruña
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Santiago de Compostela, La Coruña, Espagne, 15706
- Complejo Hospitalario Universitario de Santiago; Servicio de Neumología
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Grenoble Cedex 9, France, 38043
- CHU de Grenoble - Hôpital André Michallon
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Le Kremlin Bicetre, France, 94275
- CH de Bicetre; Pneumologie
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Lyon, France, 69004
- Hôpital de la Croix Rousse
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Montpellier, France, 34295
- Hopital Arnaud de Villeneuve
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Nantes, France, 44093
- CHU Nantes - Hôpital Laennec; Service de Pneumologie
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Nice Cedex 1, France, 06001
- CHU de Nice
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Paris, France, 75877
- Hopital Bichat Claude Bernard ; Service de Pneumologie
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Pessac, France, 33604
- CHU de Haut Leveque
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Strabourg, France, 67091
- Nouvel Hôpital Civil; Pôle de Pathologie Thoracique
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Guadalajara, Mexique, 44100
- Instituto Jalisciense de Investigacion Clinica S.A. de C.V.
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Guadalajara, Mexique, 44130
- Centro Investigacion Medico Biologica y Terapia Avanzada
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Querétaro, Mexique, 76800
- Centro Integral Médico SJR SC
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Auckland, Nouvelle-Zélande, 1051
- NZ Respiratory & Sleep Institute
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Dunedin, Nouvelle-Zélande
- Dunedin Hospital
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Tauranga, Nouvelle-Zélande, 3143
- Clinical Trials Unit, Bay of Plenty District Health Board
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Wellington, Nouvelle-Zélande
- Medical Research Inst. of New Zealand; Respiratory
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Amsterdam, Pays-Bas, 1105 AZ
- Academisch Medisch Centrum; Afdeling Longziekten, F5-258
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Hoofddorp, Pays-Bas, 2134 TM
- Spaarne Ziekenhuis Hoofddorp; Long Geneeskunde
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Nieuwegein, Pays-Bas, 3435 CM
- Antonius Ziekenhuis; Dept of Lung Diseases
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Krakow, Pologne, 31-624
- Malopolskie Centrum Alergologii
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Krakow, Pologne, 31-024
- Specjalistyczny Osrodek Alergologiczno-Internistyczny ALL-MED
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Lodz, Pologne, 90-153
- SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
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Ostrow Wielkopolski, Pologne, 63-400
- Specjalistyczna Poradnia Pulmonologiczna
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Ruda Śląska, Pologne, 41-707
- Niepubliczny Zaklad Opieki Zdrowotnej PROFILAKTYKA Wladyslaw Pierzchala
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Warszawa, Pologne, 02-507
- Klinika Chorób Wewnetrznych i Alergologii MSW
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Wrocław, Pologne, 50-220
- EMC Instytut Medyczny SA; Przychodnia przy ulicy Łowieckiej
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Caguas, Porto Rico, 00725
- San Juan Bautista School of Medicine-Clinical Research Unit
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Cidra, Porto Rico, 00739
- Advanced Medical Concepts, PSC
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Belfast, Royaume-Uni, BT9 7AB
- Belfast City Hospital; Respiratory Department
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Birmingham, Royaume-Uni, B9 5SS
- Heartlands Hospital; Respiratory Department
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Glasgow, Royaume-Uni, G51 4TF
- Royal Hospital For Children
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Glasgow, Royaume-Uni, G12 0YN
- Gartnavel General Hospital; Respiratory Department
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Glasgow, Royaume-Uni, G31 2ER
- New Lister Buliding, Level 1; Clinical Research Facility
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Hampshire, Royaume-Uni, SO16 6YD
- Southampton General Hospital; Respiratory Department
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Leicester, Royaume-Uni, LE1 5WW
- Leicester Royal Infirmary NHS Trust
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Leicester, Royaume-Uni, LE3 9QP
- Glenfield Hospital; Respiratory -Allergy Unit
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London, Royaume-Uni, SW3 6NP
- Royal Brompton Hospital; Respiratory Department
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London, Royaume-Uni, EC1A 7BE
- St Bartholomew's Hospital (Barts); Respiratory Department
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Manchester, Royaume-Uni, M23 9LT
- Wythenshawe Hospital; North West Lung Research Centre
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Newcastle upon Tyne, Royaume-Uni, NE7 7DN
- Freeman Hospital; Respiratory Department
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Plymouth, Royaume-Uni, PL6 8DH
- Derriford Hospital; The Lind Research Department
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Sheffield, Royaume-Uni, S10 2JF
- Sheffield Clinical Research Facility; National Institute for Health Research
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Levice, Slovaquie, 934 01
- ZAPA JJ Sro
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Spisska Nova Ves, Slovaquie, 052 01
- Plucna ambulancia
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Golnik, Slovénie, 4204
- University Clinic of Pulmonary and Allergic Diseases Golnik
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Brno, Tchéquie, 618 00
- Hornmed
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Liberec 1, Tchéquie, 460 63
- Nemocnice Liberec; KNL a.s. - TRN
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Nový Jičín, Tchéquie, 741-01
- Nemocnice Nový Jičín
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Rokycany, Tchéquie, 337 22
- Rokycanska nemocnice
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California
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Bakersfield, California, États-Unis, 93301
- Kern Allergy Med Clinic, Inc.
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Long Beach, California, États-Unis, 90808
- Allergy & Asthma Care Center of Southern California
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Florida
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Miami, Florida, États-Unis, 33135
- South Florida Research Center, Inc.
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Georgia
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Albany, Georgia, États-Unis, 31707
- Georgia Pollens
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New York
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New York, New York, États-Unis, 10029
- Mount Sinai Medical Center
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Oklahoma
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Tulsa, Oklahoma, États-Unis, 74136
- Allergy & Immunology
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Texas
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Houston, Texas, États-Unis, 77008
- Pioneer Research Solutions
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McKinney, Texas, États-Unis, 75069
- Metroplex Pulmonology & Sleep Center
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Washington
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Tacoma, Washington, États-Unis, 98405
- Pulmonary Consultants PLLC
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
12 ans à 75 ans (Enfant, Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La 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
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Double
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: 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.
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Lebrikizumab will be administered as SC injections every 4 weeks at dose and schedule described in arm description.
Autres noms:
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Expérimental: 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.
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Lebrikizumab will be administered as SC injections every 4 weeks at dose and schedule described in arm description.
Autres noms:
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Comparateur 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.
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Lebrikizumab will be administered as SC injections every 4 weeks at dose and schedule described in arm description.
Autres noms:
Placebo matching to lebrikizumab will be administered as SC injections every 4 weeks as per schedule described in arm description.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
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Relative Change From Baseline in Daily OCS Dose at Week 44
Délai: Baseline, Week 44
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Baseline, Week 44
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Absolute Change From Baseline in Daily OCS Dose at Week 44
Délai: Baseline, Week 44
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Baseline, Week 44
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Relative Change From Week 12 in Average OCS Dose at Week 44
Délai: Week 12, Week 44
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Week 12, Week 44
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Percentage of Participants Achieving at Least a 50 percent (%) Reduction in Their Daily OCS Dose at Week 44 Relative to Baseline
Délai: Baseline, Week 44
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Baseline, Week 44
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Percentage of Participants Discontinuing OCS Therapy or Having Achieved an Adrenal Maintenance Dose at Week 44
Délai: Week 44
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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.
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Week 44
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Percentage of Participants With Asthma Exacerbations
Délai: Baseline up to Week 44
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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.
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Baseline up to Week 44
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Percentage of Participants With Adverse Events
Délai: Baseline up to 24 weeks after last dose administration (up to a minimum of approximately 2 years)
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Baseline up to 24 weeks after last dose administration (up to a minimum of approximately 2 years)
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Percentage of Participants With Anti-therapeutic Antibodies (ATAs) Against Lebrikizumab
Délai: 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)
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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)
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Minimum Observed Serum Lebrikizumab Concentration (Cmin)
Délai: Predose (0 hours) at Weeks 4, 12, 24, 36, and 44
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Predose (0 hours) at Weeks 4, 12, 24, 36, and 44
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
28 février 2014
Achèvement primaire (Réel)
20 décembre 2016
Achèvement de l'étude (Réel)
20 décembre 2016
Dates d'inscription aux études
Première soumission
12 novembre 2013
Première soumission répondant aux critères de contrôle qualité
12 novembre 2013
Première publication (Estimation)
19 novembre 2013
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
22 mai 2017
Dernière mise à jour soumise répondant aux critères de contrôle qualité
19 mai 2017
Dernière vérification
1 mai 2017
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- WB28182
- 2012-000190-24 (Numéro EudraCT)
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
Essais cliniques sur Lebrikizumab
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Almirall, S.A.ComplétéEczéma | Dermatite atopiqueL'Autriche, Belgique, France, Allemagne, Pays-Bas, Pologne, Espagne, Royaume-Uni