A Study of Lebrikizumab in Adolescent Participants With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and a Second Controller Medication

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01875003
Collaborator
(none)
348
165
3
39.9
2.1
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
348 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Actual Study Start Date :
Aug 31, 2013
Actual Primary Completion Date :
Dec 28, 2016
Actual Study Completion Date :
Dec 28, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Lebrikizumab High

Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 micrograms [mcg] of fluticasone propionate dry powder inhaler [DPI] or equivalent) and a second controller medication, will receive SC injection of lebrikizumab (high dose) Q4W for 52 weeks during placebo-controlled period and up to 76 weeks or 104 weeks for participants who will be willing to take part in optional active-treatment extension period.

Drug: Lebrikizumab
Lebrikizumab will be administered as SC injection at high or low dose Q4W.

Drug: Standard of Care
Participants will continue to receive ICS therapy (total daily dose of 500-2000 mcg fluticasone propionate DPI or equivalent) along with at least one second controller medications (e.g. long-acting beta agonists [LABAs], leukotriene receptor antagonists (LTRAs), long-acting muscarinic antagonists (LAMAs), or theophylline) as standard of care.

Experimental: Lebrikizumab Low

Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 mcg of fluticasone propionate DPI or equivalent) and a second controller medication, will receive SC injection of lebrikizumab (low dose) Q4W for 52 weeks during placebo-controlled period and up to 76 weeks or 104 weeks for participants who will be willing to take part in optional active-treatment extension period.

Drug: Lebrikizumab
Lebrikizumab will be administered as SC injection at high or low dose Q4W.

Drug: Standard of Care
Participants will continue to receive ICS therapy (total daily dose of 500-2000 mcg fluticasone propionate DPI or equivalent) along with at least one second controller medications (e.g. long-acting beta agonists [LABAs], leukotriene receptor antagonists (LTRAs), long-acting muscarinic antagonists (LAMAs), or theophylline) as standard of care.

Placebo Comparator: Placebo

Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 mcg of fluticasone propionate DPI or equivalent) and a second controller medication, will receive SC injection of lebrikizumab matching placebo Q4W for 52 weeks during placebo-controlled period and then SC injection of lebrikizumab at high or low dose will be administered from Weeks 52 to 76 or 104 to participants who are willing to take part in optional active-treatment extension period.

Drug: Lebrikizumab
Lebrikizumab will be administered as SC injection at high or low dose Q4W.

Drug: Placebo
Lebrikizumab matching placebo will be administered as SC injection Q4W.

Drug: Standard of Care
Participants will continue to receive ICS therapy (total daily dose of 500-2000 mcg fluticasone propionate DPI or equivalent) along with at least one second controller medications (e.g. long-acting beta agonists [LABAs], leukotriene receptor antagonists (LTRAs), long-acting muscarinic antagonists (LAMAs), or theophylline) as standard of care.

Outcome Measures

Primary Outcome Measures

  1. Rate of Asthma Exacerbations During the 52-Week Placebo-Controlled Period [Baseline up to Week 52]

  2. Percentage of Participants With Adverse Events (AEs) or Serious AEs [Baseline up to Week 124]

  3. Percentage of Participants With Anti-Therapeutic Antibodies to Lebrikizumab [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 Outcome Measures

  1. Change from Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 second (FEV1) at Week 52 [Baseline , Week 52]

  2. Time to First Asthma Exacerbation [Baseline up to 52 weeks]

  3. Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 52 [Baseline , Week 52]

  4. Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and Older (AQLQ + 12) at Week 52 [Baseline, Week 52]

  5. Change From Baseline in Asthma Rescue Medication Use at Week 52 [Baseline, Week 52]

  6. Rate of Urgent Asthma-Related Health Care Utilization [Baseline up to 52 weeks]

  7. Injection Acceptability Questionnaire (IAQ) Score [Baseline up to Week 104]

Eligibility Criteria

Criteria

Ages Eligible for Study:
12 Years to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Allergy Associates of Tucson Tucson Arizona United States 85716
2 Kaiser Permanente Los Angeles Los Angeles California United States 90027
3 Southern California Research Center Mission Viejo California United States 92691
4 Allergy & Asthma Consultants Redwood City California United States 94063
5 Dignity Health Medical Foundation Sacramento California United States 95823
6 Bensch Research Associates Stockton California United States 95207
7 Allergy & Asthma Medical Group; Clinical Research Division Walnut Creek California United States 94598
8 Colorado Children's Hospital; The Breathing Institute Aurora Colorado United States 80045
9 IMMUNOe International Research Centers Centennial Colorado United States 80112
10 Asthma & Allergy; Associates, P.C. Colorado Springs Colorado United States 80907
11 National Jewish Medical and Research Center Denver Colorado United States 80206
12 Abel and Buchheim Miami Florida United States 33165
13 Compass Research East, LLC Orlando Florida United States 32806
14 Sarasota Clinical Research Sarasota Florida United States 34239
15 University of South Florida Tampa Florida United States 33613
16 Brookstone Clinical Res Ctr Columbus Georgia United States 31904
17 Georgia Pain Clinic Marietta Georgia United States
18 Rush University Medical Center Chicago Illinois United States 60612
19 The Clinical Research Center Shiloh Illinois United States 62269
20 Riley Hospital for Children; Pediatric Nephrology Indianapolis Indiana United States 46202
21 Abraham Research PLLC Florence Kentucky United States 41042
22 Breathe America Shreveport Inc Shreveport Louisiana United States 71106
23 Asthma, Allergy & Sinus Center Baltimore Maryland United States 21236
24 Boston Children's Hospital Boston Massachusetts United States 02115
25 Univ of Michigan Medical Ctr Ann Arbor Michigan United States 48109-0718
26 Cardinal Glennon Child's Hosp; Endrocrinology Saint Louis Missouri United States 63104-1095
27 Parikh Institute for Research LLC New Jersey New Jersey United States 08904
28 University of New Mexico; School of Med Albuquerque New Mexico United States 87131
29 Parikh Institute for Research LLC New York New York United States
30 Urban Health Plan, Inc. The Bronx New York United States 10459
31 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
32 Promedica Toledo Children's Hospital Toledo Ohio United States 43606
33 Bend Memorial Clinic Bend Oregon United States 97701
34 Allergy, Asthma, & Dermatology Research Center, Llc Lake Oswego Oregon United States 97035
35 Clinical Research Inst. of Southern Oregon, Pc Medford Oregon United States 97504
36 TTS Research Boerne Texas United States 78006
37 Allergy & Asthma Research Center of El Paso El Paso Texas United States 79925
38 Allergy & Asthma Res Ctr PA San Antonio Texas United States 78251
39 South Texas Allergy and Asthma Medical Professionals San Antonio Texas United States 78251
40 Bridgerland Clinical Research North Logan Utah United States 84341
41 O & O Alpan, LLC Fairfax Virginia United States 22030
42 Bellingham Asthma, Allergy & Immunology Bellingham Washington United States 98225
43 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
44 Centro Médico Vitae Buenos Aires Argentina B6500BWQ
45 Fundación Faicep Buenos Aires Argentina C1122AAK
46 Fundacion Cidea Buenos Aires Argentina C1125 ABE
47 INAER Ciudad Autónoma de Buenos Aires Argentina C1425BEN
48 INSARES Mendoza, Mendoza City Argentina M5500CCG
49 Instituto Respirar Mendoza Argentina 5500
50 Centro Respiratorio Infantil Rosario Argentina 2000
51 Investigaciones en Patologias Respiratorias San Miguel de Tucuman Argentina 4000
52 Centro Integral de Medicina Respiratoria (CIMER) San Miguel de Tucumán Argentina T4000CHE
53 Instituto Del Buen Aire Santa Fe Argentina 3000
54 Sanatorio Británico de Rosario Santa Fé Argentina
55 CEMER Centro Médico de Enfermedades Respiratorias Vicente López Argentina B1602DQD
56 Centro de Referencia em Enfermidades Respiratorias e Alergia - CEAR Salvador BA Brazil 41940-455
57 Santa Casa de Misericordia de Porto Alegre Porto Alegre RS Brazil 90020-090
58 Hospital Sao Lucas - PUCRS Porto Alegre RS Brazil 90610-000
59 Faculdade de Medicina do ABC - FMABC Santo Andre SP Brazil 09060-650
60 Pesquisare Saúde Sociedade Simples Santo Andre SP Brazil 09080-000
61 Hospital Alemao Oswaldo Cruz; Pesquisa Clinica Sao Paulo SP Brazil 01323-020
62 Instituto de Pesquisa Clínica e Medicina Avançada Ltda Sao Paulo SP Brazil 05437-010
63 CMPC/Clinica de Alergia Martti Antila Sorocaba SP Brazil 18040-425
64 Dr. Tharwat A. Fera Inc. Vancouver British Columbia Canada V5Z 4E1
65 Brian Lyttle's Private Practice London Ontario Canada N6A 5B8
66 Centre de Recherche Applique En Allergie de Quebec Quebec City Quebec Canada G1V 4M6
67 Hospital Santa Clara Bogota Colombia
68 Hospital Pablo Tobon Uribe Medellin-Antioquia Colombia
69 Hofstetr Alois MUDr. s.r.o. Jihlava Czechia 586 01
70 Alergologie Teplice, s.r.o. Teplice Czechia 415 01
71 Groupe Hospitalier Pellegrin; Pharmacie Bordeaux France 33076
72 Groupe Hospitalier Necker Enfants Malades Paris France 75015
73 Hopital Armand Trousseau Paris France 75571
74 Hopital Charles Nicolle; cic Rouen France 76031
75 Universitaetsklinikum Frankfurt Frankfurt Germany 60528
76 Evangelisches Krankenhaus Hamm Hamm Germany 59063
77 Praxis Dr. med. Jan Feimer München Germany 80539
78 Semmelweis Egyetem Budapest Hungary 1083
79 Heim Pál Gyermekkórház Budapest Hungary 1089
80 Kenezy Korhaz Rendelointezet Debrecen Hungary 4031
81 Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház Miskolc Hungary 3526
82 Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ Szeged Hungary 6720
83 Papp és Társa Bt. Szigetvár Hungary 7900
84 Tudogyogyintezet Torokbalint Torokbalint Hungary 2045
85 Barzilai Medical Center Ashkelon Israel 78278
86 Rambam Health Care Campus Haifa Israel 31096
87 Shaare Zedek Medical Center Jerusalem Israel 91031
88 Schneider Children's Medical Center Petach-Tikva Israel 49100
89 Chaim Sheba Medical Center Tel Hashomer Israel 52661
90 Azienda Policlinico Umberto I; Dipartimento Integrato di Pediatria e Neuropsichiatria Infantile Roma Lazio Italy 00161
91 Ospedale Pediatrico Bambino Gesu Roma Lazio Italy 00165
92 Fondazione IRCCS Policlinico San Matteo Pavia Lombardia Italy 27100
93 Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele Catania Sicilia Italy 95123
94 National Hospital Organization Mie Hospital Tsu-shi Japan 514-0125
95 National Hospital Organization Shimoshizu National Hospital Yotsukaido Japan 284-0003
96 Inha University Hospital Incheon Korea, Republic of 22332
97 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 03722
98 KyungHee Medical Center Seoul Korea, Republic of 130-702
99 Instituto Nacional de Pediatría Ciudad De México Mexico 04530
100 Grupo Medico Camino DF Mexico 03310
101 Instituto Jalisciense de Investigacion Clinica S.A. de C.V. Guadalajara Mexico 44100
102 Centro de Investigacion Medico Biologico y Terapia Avanzada, S.C. Guadalajara Mexico 44130
103 Unidad Medica de Occidente Guadalajara Mexico 44220
104 Hospital Universitario Dr. Jose Eleuterio González; Enfermedades Pulmonares Crónicas Monterrey Mexico 64460
105 Unidad de Investigacion Clinica En Medicina (Udicem) S.C. Monterrey Mexico 64718
106 Consultorio Especialidad Alergologia Pediatrica Villahermosa Mexico 86035
107 Hospital Dos de Mayo; Parque Historia De la Medicina Peruana S/n Lima Peru Lima 01
108 Hospital Nacional Luis N Saenz PNP Lima Peru Lima 11
109 Clinica Internacional Lima Peru Lima 1
110 Centro de Investigación Ricardo Palma Lima Peru LIMA 27
111 Clinica Anglo Americana Lima Peru Lima 27
112 Clinica San Borja Lima Peru Lima 41
113 Prywatna Praktyka Lekarska Bialystok Poland 15-430
114 Malopolskie Centrum Alergologii Krakow Poland 31-624
115 SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi Lodz Poland 90-153
116 Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi Lodz Poland 93-513
117 Centrum Alergologii NZOZ Lublin Poland 20-552
118 Centrum Alergologii Teresa Hofman Poznan Poland 60-214
119 ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. z o. o Tarnow Poland 33-100
120 Klinika Chorób Wewnetrznych i Alergologii MSW Warszawa Poland 02-507
121 Hospital Infante D. Pedro; Servico de Imunoalergologia Aveiro Portugal 3814-501
122 Hospital Particular do Algarve - Unidade de Faro Faro Portugal 8005-226
123 Hospital Dona Estefania; Servico de Imunoalergologia Lisboa Portugal 1169-045
124 Hospital CUF Porto; Servico de Imunoalergologia Senhora da Hora - Porto Portugal 4460-188
125 Alersa Kosice Slovakia 040 11
126 ALERGOMEA s.r.o. Lucenec Slovakia 984 01
127 Imunoalergologia Dzurilla s.r.o. Nitra Slovakia 949 01
128 Uni of Cape Town Lung Inst. Cape Town South Africa 7925
129 Westville Hospital Durban South Africa 3630
130 Sebastian Peter Durban South Africa 4001
131 WWCT Lakeview Hospital Johannesburg South Africa 1501
132 Medicross Sophiatown Johannesburg South Africa 2113
133 GCT Mercantile; Clinical Research Centre Port Elizabeth South Africa 6014
134 Bothe ke Bontle Health Services Pretoria South Africa 0101
135 Soweto Clinical Trial Centre Soweto South Africa 1818
136 Limpopo Clinical Research Initiative; Tamboti Medical Centre Tabazimbi South Africa 0380
137 Hospital Universitario Germans Trias i Pujol; Servicio de Farmacia Badalona Barcelona Spain 08916
138 Hospital Sant Joan De Deu Esplugues De Llobregas Barcelona Spain 08950
139 Corporacio Sanitaria Parc Tauli; Servicio de Oncologia Sabadell Barcelona Spain 08208
140 Hospital de Manises Manises Valencia Spain 46940
141 Hospital Quiron Teknon Barcelona Spain 08017
142 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
143 Clínica Dr. Lobatón Cadiz Spain 11008
144 Clinica Ojeda de Asma Y Alergia Madrid Spain 28006
145 Hospital Regional Universitario Carlos Haya Malaga Spain 29010
146 Chung Shan M. U. H. Taichung Taiwan 402
147 China Medical University Hospital Taichung Taiwan 40447
148 Taichung Veterans General Hospital Taichung Taiwan 407
149 National Cheng Kung Univ Hosp Tainan Taiwan 00704
150 Chang Gung Memorial Hospital Taoyuan Taiwan 333
151 Municipal Medical Institution; Chernivtsi Regional Children's Hospital Chernivtsi Ukraine 58023
152 Public Institution City Clinical Hospital # 6 of Dnipropetrovsk Regional Board Dnepropetrovsk Ukraine 49000
153 State Institution of Pediatrics Obstetrics and Gynecology of NAMSU Kiev Ukraine 04050
154 Municipal Institution "Kryvyi Rih City Clinical Hospital #8" of Dnipropetrovsk Regional Council Kryvyi Rih Ukraine 50082
155 SI National Institute of Phthisiology and Pulmonology n.a. F.G.Yanovskyi under NAMS of Ukraine Kyiv Ukraine 03680
156 SI Research Centre of Radiation Medicine of AMSU Kyiv Ukraine 3115
157 Municipal Institution Zaporizhzhya Regional Clinical Child Hospital Zaporizhzhya Ukraine 69063
158 Birmingham Children's Hospital NHS Foundation Trust Birmingham United Kingdom B4 6NH
159 Birmingham Heartlands Hospital Birmingham United Kingdom B9 5SS
160 Dumfries and Galloway Royal Infirmary; Department of Paediatrics Dumfries United Kingdom DG1 4AP
161 Royal Hospital For Children Glasgow United Kingdom G51 4TF
162 University of Leicester Leicester United Kingdom LE1 7RH
163 Royal Brompton Hospital; Respiratory Department London United Kingdom SW3 6NP
164 Sheffield Childrens Hospital Sheffield United Kingdom S102TH
165 Southampton General Hospital Southampton United Kingdom SO16 6YD

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:
NCT01875003
Other Study ID Numbers:
  • WB28183
  • 2012-000180-25
First Posted:
Jun 11, 2013
Last Update Posted:
May 16, 2017
Last Verified:
May 1, 2017
Studies a U.S. FDA-regulated Drug Product:
Yes
Additional relevant MeSH terms:

Study Results

No Results Posted as of May 16, 2017