A Study of Lebrikizumab in Adolescent Participants With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and a Second Controller Medication
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 |
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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.
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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.
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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
- Rate of Asthma Exacerbations During the 52-Week Placebo-Controlled Period [Baseline up to Week 52]
- Percentage of Participants With Adverse Events (AEs) or Serious AEs [Baseline up to Week 124]
- 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
- Change from Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 second (FEV1) at Week 52 [Baseline , Week 52]
- Time to First Asthma Exacerbation [Baseline up to 52 weeks]
- Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 52 [Baseline , Week 52]
- Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and Older (AQLQ + 12) at Week 52 [Baseline, Week 52]
- Change From Baseline in Asthma Rescue Medication Use at Week 52 [Baseline, Week 52]
- Rate of Urgent Asthma-Related Health Care Utilization [Baseline up to 52 weeks]
- Injection Acceptability Questionnaire (IAQ) Score [Baseline up to Week 104]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Asthma diagnosis for greater than or equal to (>/=) 12 months prior to Visit 1
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Bronchodilator response during screening
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Pre-bronchodilator FEV1 of 40 percent (%) - 90% predicted at both Visits 2 and 3
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On high dose ICS therapy for >/= 6 months prior to Visit 1
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On an eligible second controller medication for 6 months prior to Visit 1
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Uncontrolled asthma as defined by the protocol both during screening and at the time of randomization
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Demonstrated adherence with controller medication during the screening period
Exclusion Criteria:
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History of severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
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Maintenance oral corticosteroid therapy within 3 months prior to Visit 1
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Treatment with systemic (oral, intravenous [IV], or intramuscular [IM]) corticosteroids within 4 weeks prior to Visit 1 or during the screening period
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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
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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
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History of active tuberculosis requiring treatment
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Known immunodeficiency, including, but not limited to, human immunodeficiency virus (HIV) infection
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Evidence of acute or chronic hepatitis or known liver cirrhosis
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History of cystic fibrosis, bronchiectasis, and/or other clinically significant lung disease other than asthma
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Diagnosis or history of malignancy or current evaluation for potential malignancy
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Current smoker or former smoker with a history of greater than (>) 10 pack-years
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History of alcohol or drug abuse
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Past and/or current use of any anti- interleukin (IL) -13 or anti-IL-4/IL-13 therapy, including lebrikizumab
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Use of other monoclonal antibody therapy, including omalizumab, within 6 months or 5 drug half-lives (whichever is longer) prior to Visit 1
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Initiation of or change in allergen immunotherapy within 3 months prior to Visit 1 or during screening
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History of bronchial thermoplasty
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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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.- WB28183
- 2012-000180-25