Clinical trial NCT01987492: A Study of Lebrikizumab (RO5490255) in Participants With Severe Oral Corticosteroids (OCS) Dependent Asthma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-11-19
Enrollment: 230
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Relative Change From Baseline in Daily OCS Dose at Week 44
timeFrame: Baseline, Week 44
Secondary outcomes:
measure: Absolute Change From Baseline in Daily OCS Dose at Week 44
timeFrame: Baseline, Week 44
measure: Relative Change From Week 12 in Average OCS Dose at Week 44
timeFrame: Week 12, Week 44
measure: Percentage of Participants Achieving at Least a 50 percent (%) Reduction in Their Daily OCS Dose at Week 44 Relative to Baseline
timeFrame: Baseline, Week 44
measure: Percentage of Participants Discontinuing OCS Therapy or Having Achieved an Adrenal Maintenance Dose at Week 44
timeFrame: Week 44
measure: Percentage of Participants With Asthma Exacerbations
timeFrame: Baseline up to Week 44
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to 24 weeks after last dose administration (up to a minimum of approximately 2 years)
measure: Percentage of Participants With Anti-therapeutic Antibodies (ATAs) Against Lebrikizumab
timeFrame: 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)
measure: Minimum Observed Serum Lebrikizumab Concentration (Cmin)
timeFrame: Predose (0 hours) at Weeks 4, 12, 24, 36, and 44
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Kern Allergy Med Clinic, Inc.
state: California
city: Long Beach
country: United States
facility: Allergy & Asthma Care Center of Southern California
state: California
city: Miami
country: United States
facility: South Florida Research Center, Inc.
state: Florida
city: Albany
country: United States
facility: Georgia Pollens
state: Georgia
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Tulsa
country: United States
facility: Allergy & Immunology
state: Oklahoma
city: Houston
country: United States
facility: Pioneer Research Solutions
state: Texas
city: McKinney
country: United States
facility: Metroplex Pulmonology & Sleep Center
state: Texas
city: Tacoma
country: United States
facility: Pulmonary Consultants PLLC
state: Washington
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital, Department of Respiratory and Sleep Medicine
state: Queensland
city: Clayton
country: Australia
facility: Monash Medical Centre; Respiratory and Sleep Medicine
state: Victoria
city: Nedlands
country: Australia
facility: Institute for Respiratory Health Inc
state: Western Australia
city: Bruxelles
country: Belgium
facility: Clin Univ de Bxl Hôpital Erasme
city: Genk
country: Belgium
facility: Longartsenpraktijk
city: Gent
country: Belgium
facility: UZ Gent
city: Toronto
country: Canada
facility: Inspiration Research Limited
state: Ontario
city: Brno
country: Czechia
facility: Hornmed
city: Liberec 1
country: Czechia
facility: Nemocnice Liberec; KNL a.s. - TRN
city: Nový Jičín
country: Czechia
facility: Nemocnice Nový Jičín
city: Rokycany
country: Czechia
facility: Rokycanska nemocnice
city: Hellerup
country: Denmark
facility: Gentofte Hospital, Klinik for Allergi
city: Grenoble Cedex 9
country: France
facility: CHU de Grenoble - Hôpital André Michallon
city: Le Kremlin Bicetre
country: France
facility: CH de Bicetre; Pneumologie
city: Lyon
country: France
facility: Hôpital de La Croix Rousse
city: Montpellier
country: France
facility: Hôpital Arnaud de Villeneuve
city: Nantes
country: France
facility: CHU Nantes - Hôpital Laennec; Service de Pneumologie
city: Nice Cedex 1
country: France
facility: CHU de Nice
city: Paris
country: France
facility: Hopital Bichat Claude Bernard ; Service de Pneumologie
city: Pessac
country: France
facility: CHU de Haut Leveque
city: Strabourg
country: France
facility: Nouvel Hôpital Civil; Pôle de Pathologie Thoracique
city: Guadalajara
country: Mexico
facility: Instituto Jalisciense de Investigacion Clinica S.A. de C.V.
city: Guadalajara
country: Mexico
facility: Centro Investigacion Medico Biologica y Terapia Avanzada
city: Querétaro
country: Mexico
facility: Centro Integral Médico SJR SC
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum; Afdeling Longziekten, F5-258
city: Hoofddorp
country: Netherlands
facility: Spaarne Ziekenhuis Hoofddorp; Long Geneeskunde
city: Nieuwegein
country: Netherlands
facility: Antonius Ziekenhuis; Dept of Lung Diseases
city: Auckland
country: New Zealand
facility: NZ Respiratory & Sleep Institute
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Tauranga
country: New Zealand
facility: Clinical Trials Unit, Bay of Plenty District Health Board
city: Wellington
country: New Zealand
facility: Medical Research Inst. of New Zealand; Respiratory
city: Krakow
country: Poland
facility: Specjalistyczny Osrodek Alergologiczno-Internistyczny ALL-MED
city: Krakow
country: Poland
facility: Malopolskie Centrum Alergologii
city: Lodz
country: Poland
facility: SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
city: Ostrow Wielkopolski
country: Poland
facility: Specjalistyczna Poradnia Pulmonologiczna
city: Ruda Śląska
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej PROFILAKTYKA Wladyslaw Pierzchala
city: Warszawa
country: Poland
facility: Klinika Chorób Wewnetrznych i Alergologii MSW
city: Wrocław
country: Poland
facility: EMC Instytut Medyczny SA; Przychodnia przy ulicy Łowieckiej
city: Caguas
country: Puerto Rico
facility: San Juan Bautista School of Medicine-Clinical Research Unit
city: Cidra
country: Puerto Rico
facility: Advanced Medical Concepts, PSC
city: Levice
country: Slovakia
facility: ZAPA JJ Sro
city: Spisska Nova Ves
country: Slovakia
facility: Plucna ambulancia
city: Golnik
country: Slovenia
facility: University Clinic of Pulmonary and Allergic Diseases Golnik
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago; Servicio de Neumología
state: La Coruña
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu; i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca; Servicio de Neumologia
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Belfast
country: United Kingdom
facility: Belfast City Hospital; Respiratory Department
city: Birmingham
country: United Kingdom
facility: Heartlands Hospital; Respiratory Department
city: Glasgow
country: United Kingdom
facility: Gartnavel General Hospital; Respiratory Department
city: Glasgow
country: United Kingdom
facility: New Lister Buliding, Level 1; Clinical Research Facility
city: Glasgow
country: United Kingdom
facility: Royal Hospital For Children
city: Hampshire
country: United Kingdom
facility: Southampton General Hospital; Respiratory Department
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary NHS Trust
city: Leicester
country: United Kingdom
facility: Glenfield Hospital; Respiratory -Allergy Unit
city: London
country: United Kingdom
facility: St Bartholomew's Hospital (Barts); Respiratory Department
city: London
country: United Kingdom
facility: Royal Brompton Hospital; Respiratory Department
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital; North West Lung Research Centre
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital; Respiratory Department
city: Plymouth
country: United Kingdom
facility: Derriford Hospital; The Lind Research Department
city: Sheffield
country: United Kingdom
facility: Sheffield Clinical Research Facility; National Institute for Health Research
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: