Clinical trial NCT01875003: A Study of Lebrikizumab in Adolescent Participants With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and a Second Controller Medication
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-06-11
Enrollment: 348
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
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, safety, and tolerability of lebrikizumab in adolescent participants with asthma whose disease remains uncontrolled despite daily treatment with inhaled corticosteroids (ICS) therapy and at least one second controller medication. Participants will be randomized in a 1:1:1 ratio to receive double-blind treatment with either lebrikizumab ('High' or 'Low') or placebo, administered as subcutaneous (SC) every 4 weeks (Q4W) for 52 weeks, in addition to their standard-of-care therapy. This will be followed by an optional 52-week double-blind active-treatment extension. The anticipated time on study treatment is up to 104 weeks. Participants who complete the study to Week 104, discontinue prematurely or decide not to take part in the optional active-treatment extension will transition to the 20-week safety follow-up period.


Eligibility criteria: Inclusion Criteria:

* Asthma diagnosis for greater than or equal to (\>/=) 12 months prior to Visit 1
* Bronchodilator response during screening
* Pre-bronchodilator FEV1 of 40 percent (%) - 90% predicted at both Visits 2 and 3
* On high dose ICS therapy for \>/= 6 months prior to Visit 1
* On an eligible second controller medication for 6 months prior to Visit 1
* Uncontrolled asthma as defined by the protocol both during screening and at the time of randomization
* Demonstrated adherence with controller medication during the screening period

Exclusion Criteria:

* History of severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
* Maintenance oral corticosteroid therapy within 3 months prior to Visit 1
* Treatment with systemic (oral, intravenous \[IV\], or intramuscular \[IM\]) corticosteroids within 4 weeks prior to Visit 1 or during the screening period
* Treatment with intra-articular corticosteroids within 4 weeks prior to Visit 1 or during the screening period or anticipated need for intra-articular corticosteroids during the course of the study
* Infection that meets the following criteria: Any infection requiring hospital admission or requiring treatment with IV or IM antibiotics within 4 weeks prior to Visit 1 or during screening; any active infection that required treatment with oral antibiotics within 2 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
* History of active tuberculosis requiring treatment
* Known immunodeficiency, including, but not limited to, human immunodeficiency virus (HIV) infection
* Evidence of acute or chronic hepatitis or known liver cirrhosis
* History of cystic fibrosis, bronchiectasis, and/or other clinically significant lung disease other than asthma
* Diagnosis or history of malignancy or current evaluation for potential malignancy
* Current smoker or former smoker with a history of greater than (\>) 10 pack-years
* History of alcohol or drug abuse
* Past and/or current use of any anti- interleukin (IL) -13 or anti-IL-4/IL-13 therapy, including lebrikizumab
* Use of other monoclonal antibody therapy, including omalizumab, within 6 months or 5 drug half-lives (whichever is longer) prior to Visit 1
* Initiation of or change in allergen immunotherapy within 3 months prior to Visit 1 or during screening
* History of bronchial thermoplasty

Primary outcomes:
measure: Rate of Asthma Exacerbations During the 52-Week Placebo-Controlled Period
timeFrame: Baseline up to Week 52
measure: Percentage of Participants With Adverse Events (AEs) or Serious AEs
timeFrame: Baseline up to Week 124
measure: Percentage of Participants With Anti-Therapeutic Antibodies to Lebrikizumab
timeFrame: Baseline up to Week 124 (assessed at Baseline, Weeks 4, 12, 24, 36, 52, 76, 104, 112, and 124 or at early termination [up to 108 weeks])
Secondary outcomes:
measure: Change from Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 second (FEV1) at Week 52
timeFrame: Baseline , Week 52
measure: Time to First Asthma Exacerbation
timeFrame: Baseline up to 52 weeks
measure: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 52
timeFrame: Baseline , Week 52
measure: Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and Older (AQLQ + 12) at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Asthma Rescue Medication Use at Week 52
timeFrame: Baseline, Week 52
measure: Rate of Urgent Asthma-Related Health Care Utilization
timeFrame: Baseline up to 52 weeks
measure: Injection Acceptability Questionnaire (IAQ) Score
timeFrame: Baseline up to Week 104
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Allergy Associates of Tucson
state: Arizona
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles
state: California
city: Mission Viejo
country: United States
facility: Southern California Research Center
state: California
city: Redwood City
country: United States
facility: Allergy & Asthma Consultants
state: California
city: Sacramento
country: United States
facility: Dignity Health Medical Foundation
state: California
city: Stockton
country: United States
facility: Bensch Research Associates
state: California
city: Walnut Creek
country: United States
facility: Allergy & Asthma Medical Group; Clinical Research Division
state: California
city: Aurora
country: United States
facility: Colorado Children's Hospital; The Breathing Institute
state: Colorado
city: Centennial
country: United States
facility: IMMUNOe International Research Centers
state: Colorado
city: Colorado Springs
country: United States
facility: Asthma & Allergy; Associates, P.C.
state: Colorado
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Miami
country: United States
facility: Abel and Buchheim
state: Florida
city: Orlando
country: United States
facility: Compass Research East, LLC
state: Florida
city: Sarasota
country: United States
facility: Sarasota Clinical Research
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Columbus
country: United States
facility: Brookstone Clinical Res Ctr
state: Georgia
city: Marietta
country: United States
facility: Georgia Pain Clinic
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Shiloh
country: United States
facility: The Clinical Research Center
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children; Pediatric Nephrology
state: Indiana
city: Florence
country: United States
facility: Abraham Research PLLC
state: Kentucky
city: Shreveport
country: United States
facility: Breathe America Shreveport Inc
state: Louisiana
city: Baltimore
country: United States
facility: Asthma, Allergy & Sinus Center
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Univ of Michigan Medical Ctr
state: Michigan
city: Saint Louis
country: United States
facility: Cardinal Glennon Child's Hosp; Endrocrinology
state: Missouri
city: New Jersey
country: United States
facility: Parikh Institute for Research LLC
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico; School of Med
state: New Mexico
city: New York
country: United States
facility: Parikh Institute for Research LLC
state: New York
city: The Bronx
country: United States
facility: Urban Health Plan, Inc.
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Toledo
country: United States
facility: Promedica Toledo Children's Hospital
state: Ohio
city: Bend
country: United States
facility: Bend Memorial Clinic
state: Oregon
city: Lake Oswego
country: United States
facility: Allergy, Asthma, & Dermatology Research Center, Llc
state: Oregon
city: Medford
country: United States
facility: Clinical Research Inst. of Southern Oregon, Pc
state: Oregon
city: Boerne
country: United States
facility: TTS Research
state: Texas
city: El Paso
country: United States
facility: Allergy & Asthma Research Center of El Paso
state: Texas
city: San Antonio
country: United States
facility: Allergy & Asthma Res Ctr PA
state: Texas
city: San Antonio
country: United States
facility: South Texas Allergy and Asthma Medical Professionals
state: Texas
city: North Logan
country: United States
facility: Bridgerland Clinical Research
state: Utah
city: Fairfax
country: United States
facility: O & O Alpan, LLC
state: Virginia
city: Bellingham
country: United States
facility: Bellingham Asthma, Allergy & Immunology
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Centro Médico Vitae
city: Buenos Aires
country: Argentina
facility: Fundación Faicep
city: Buenos Aires
country: Argentina
facility: Fundacion Cidea
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: INAER
city: Mendoza, Mendoza City
country: Argentina
facility: INSARES
city: Mendoza
country: Argentina
facility: Instituto Respirar
city: Rosario
country: Argentina
facility: Centro Respiratorio Infantil
city: San Miguel de Tucuman
country: Argentina
facility: Investigaciones en Patologias Respiratorias
city: San Miguel de Tucumán
country: Argentina
facility: Centro Integral de Medicina Respiratoria (CIMER)
city: Santa Fe
country: Argentina
facility: Instituto Del Buen Aire
city: Santa Fé
country: Argentina
facility: Sanatorio Británico de Rosario
city: Vicente López
country: Argentina
facility: CEMER Centro Médico de Enfermedades Respiratorias
city: Salvador
country: Brazil
facility: Centro de Referencia em Enfermidades Respiratorias e Alergia - CEAR
state: BA
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
state: RS
city: Santo Andre
country: Brazil
facility: Faculdade de Medicina do ABC - FMABC
state: SP
city: Santo Andre
country: Brazil
facility: Pesquisare Saúde Sociedade Simples
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz; Pesquisa Clinica
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto de Pesquisa Clínica e Medicina Avançada Ltda
state: SP
city: Sorocaba
country: Brazil
facility: CMPC/Clinica de Alergia Martti Antila
state: SP
city: Vancouver
country: Canada
facility: Dr. Tharwat A. Fera Inc.
state: British Columbia
city: London
country: Canada
facility: Brian Lyttle's Private Practice
state: Ontario
city: Quebec City
country: Canada
facility: Centre de Recherche Applique En Allergie de Quebec
state: Quebec
city: Bogota
country: Colombia
facility: Hospital Santa Clara
city: Medellin-Antioquia
country: Colombia
facility: Hospital Pablo Tobon Uribe
city: Jihlava
country: Czechia
facility: Hofstetr Alois MUDr. s.r.o.
city: Teplice
country: Czechia
facility: Alergologie Teplice, s.r.o.
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin; Pharmacie
city: Paris
country: France
facility: Groupe Hospitalier Necker Enfants Malades
city: Paris
country: France
facility: Hopital Armand Trousseau
city: Rouen
country: France
facility: Hopital Charles Nicolle; cic
city: Frankfurt
country: Germany
facility: Universitaetsklinikum Frankfurt
city: Hamm
country: Germany
facility: Evangelisches Krankenhaus Hamm
city: München
country: Germany
facility: Praxis Dr. med. Jan Feimer
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Heim Pál Gyermekkórház
city: Debrecen
country: Hungary
facility: Kenezy Korhaz Rendelointezet
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
city: Szigetvár
country: Hungary
facility: Papp és Társa Bt.
city: Torokbalint
country: Hungary
facility: Tudogyogyintezet Torokbalint
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petach-Tikva
country: Israel
facility: Schneider Children's Medical Center
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Roma
country: Italy
facility: Azienda Policlinico Umberto I; Dipartimento Integrato di Pediatria e Neuropsichiatria Infantile
state: Lazio
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesu
state: Lazio
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
state: Lombardia
city: Catania
country: Italy
facility: Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele
state: Sicilia
city: Tsu-shi
country: Japan
facility: National Hospital Organization Mie Hospital
city: Yotsukaido
country: Japan
facility: National Hospital Organization Shimoshizu National Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: KyungHee Medical Center
city: Ciudad De México
country: Mexico
facility: Instituto Nacional de Pediatría
city: DF
country: Mexico
facility: Grupo Medico Camino
city: Guadalajara
country: Mexico
facility: Instituto Jalisciense de Investigacion Clinica S.A. de C.V.
city: Guadalajara
country: Mexico
facility: Centro de Investigacion Medico Biologico y Terapia Avanzada, S.C.
city: Guadalajara
country: Mexico
facility: Unidad Medica de Occidente
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio González; Enfermedades Pulmonares Crónicas
city: Monterrey
country: Mexico
facility: Unidad de Investigacion Clinica En Medicina (Udicem) S.C.
city: Villahermosa
country: Mexico
facility: Consultorio Especialidad Alergologia Pediatrica
city: Lima
country: Peru
facility: Hospital Dos de Mayo; Parque Historia De la Medicina Peruana S/n
city: Lima
country: Peru
facility: Hospital Nacional Luis N Saenz PNP
city: Lima
country: Peru
facility: Clinica Internacional
city: Lima
country: Peru
facility: Centro de Investigación Ricardo Palma
city: Lima
country: Peru
facility: Clinica Anglo Americana
city: Lima
country: Peru
facility: Clinica San Borja
city: Bialystok
country: Poland
facility: Prywatna Praktyka Lekarska
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: Lodz
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi
city: Lublin
country: Poland
facility: Centrum Alergologii NZOZ
city: Poznan
country: Poland
facility: Centrum Alergologii Teresa Hofman
city: Tarnow
country: Poland
facility: ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. z o. o
city: Warszawa
country: Poland
facility: Klinika Chorób Wewnetrznych i Alergologii MSW
city: Aveiro
country: Portugal
facility: Hospital Infante D. Pedro; Servico de Imunoalergologia
city: Faro
country: Portugal
facility: Hospital Particular do Algarve - Unidade de Faro
city: Lisboa
country: Portugal
facility: Hospital Dona Estefania; Servico de Imunoalergologia
city: Senhora da Hora - Porto
country: Portugal
facility: Hospital CUF Porto; Servico de Imunoalergologia
city: Kosice
country: Slovakia
facility: Alersa
city: Lucenec
country: Slovakia
facility: ALERGOMEA s.r.o.
city: Nitra
country: Slovakia
facility: Imunoalergologia Dzurilla s.r.o.
city: Cape Town
country: South Africa
facility: Uni of Cape Town Lung Inst.
city: Durban
country: South Africa
facility: Westville Hospital
city: Durban
country: South Africa
facility: Sebastian Peter
city: Johannesburg
country: South Africa
facility: WWCT Lakeview Hospital
city: Johannesburg
country: South Africa
facility: Medicross Sophiatown
city: Port Elizabeth
country: South Africa
facility: GCT Mercantile; Clinical Research Centre
city: Pretoria
country: South Africa
facility: Bothe ke Bontle Health Services
city: Soweto
country: South Africa
facility: Soweto Clinical Trial Centre
city: Tabazimbi
country: South Africa
facility: Limpopo Clinical Research Initiative; Tamboti Medical Centre
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol; Servicio de Farmacia
state: Barcelona
city: Esplugues De Llobregas
country: Spain
facility: Hospital Sant Joan De Deu
state: Barcelona
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
state: Barcelona
city: Manises
country: Spain
facility: Hospital de Manises
state: Valencia
city: Barcelona
country: Spain
facility: Hospital Quiron Teknon
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Cadiz
country: Spain
facility: Clínica Dr. Lobatón
city: Madrid
country: Spain
facility: Clinica Ojeda de Asma Y Alergia
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya
city: Taichung
country: Taiwan
facility: Chung Shan M. U. H.
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung Univ Hosp
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Chernivtsi
country: Ukraine
facility: Municipal Medical Institution; Chernivtsi Regional Children's Hospital
city: Dnepropetrovsk
country: Ukraine
facility: Public Institution City Clinical Hospital # 6 of Dnipropetrovsk Regional Board
city: Kiev
country: Ukraine
facility: State Institution of Pediatrics Obstetrics and Gynecology of NAMSU
city: Kryvyi Rih
country: Ukraine
facility: Municipal Institution "Kryvyi Rih City Clinical Hospital #8" of Dnipropetrovsk Regional Council
city: Kyiv
country: Ukraine
facility: SI National Institute of Phthisiology and Pulmonology n.a. F.G.Yanovskyi under NAMS of Ukraine
city: Kyiv
country: Ukraine
facility: SI Research Centre of Radiation Medicine of AMSU
city: Zaporizhzhya
country: Ukraine
facility: Municipal Institution Zaporizhzhya Regional Clinical Child Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital NHS Foundation Trust
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Dumfries
country: United Kingdom
facility: Dumfries and Galloway Royal Infirmary; Department of Paediatrics
city: Glasgow
country: United Kingdom
facility: Royal Hospital For Children
city: Leicester
country: United Kingdom
facility: University of Leicester
city: London
country: United Kingdom
facility: Royal Brompton Hospital; Respiratory Department
city: Sheffield
country: United Kingdom
facility: Sheffield Childrens Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Szefler SJ, Roberts G, Rubin AS, Zielen S, Kuna P, Alpan O, Anzures-Cabrera J, Chen Q, Holweg CTJ, Kaminski J, Putnam WS, Matthews JG, Kamath N. Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS). Clin Transl Allergy. 2022 Jul 14;12(7):e12176. doi: 10.1002/clt2.12176. eCollection 2022 Jul.