Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With Exacerbation History (TERRANOVA)

A Randomised, Double-blind, Double Dummy, 56 Week Placebo-controlled, Multicentre, Parallel Group, Phase 3 Study Evaluating Efficacy/Safety of 3 Benralizumab Doses in Patients With Moderate to Very Severe COPD With Previous Exacerbations.

The purpose of the study is to determine if benralizumab reduces COPD exacerbation rate in symptomatic patients with moderate to very severe COPD who are receiving standard of care therapies.

Study Overview

• Status: Completed
• Conditions: Moderate to Very Severe Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Benralizumab Arm A; Drug: Benralizumab Arm B; Drug: Benralizumab Arm C; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 2255
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1414AIF
    • Research Site
  • Caba, Argentina, C1425BEN
    • Research Site
  • Caba, Argentina, C1056ABJ
    • Research Site
  • Caba, Argentina, 1426
    • Research Site
  • Caba, Argentina, C1431FWO
    • Research Site
  • Ciudad Autónoma de Buenos Aire, Argentina, C1440BRR
    • Research Site
  • Ciudad de Buenos Aires, Argentina, 1425
    • Research Site
  • Concepción del Uruguay, Argentina, 3260
    • Research Site
  • Corrientes, Argentina, 3400
    • Research Site
  • Córdoba, Argentina, X5003DCE
    • Research Site
  • Córdoba, Argentina, X5014KEH
    • Research Site
  • Florencio Varela, Argentina, 1888
    • Research Site
  • Florida, Argentina, 1638
    • Research Site
  • Mar del Plata, Argentina, 7600
    • Research Site
  • Mar del Plata, Argentina, B7600GNY
    • Research Site
  • Mendoza, Argentina, 5500
    • Research Site
  • Mendoza, Argentina, M5500GIP
    • Research Site
  • Nueve de julio, Argentina, B6500EZL
    • Research Site
  • Quilmes, Argentina, B1878FNR
    • Research Site
  • Rosario, Argentina, S2000DEJ
    • Research Site
  • San Fernando, Argentina, 1646
    • Research Site
  • San Miguel de Tucuman, Argentina, T4000IAR
    • Research Site
• Australia
  • Clayton, Australia, 3168
    • Research Site
  • Gosford, Australia, 2250
    • Research Site
  • Murdoch, Australia, 6150
    • Research Site
  • Nedlands, Australia, 6009
    • Research Site
  • New Lambton, Australia, 2310
    • Research Site
  • Woolloongabba, Australia, 4102
    • Research Site
• Belgium
  • Brussels, Belgium, 1020
    • Research Site
  • Genk, Belgium, 3600
    • Research Site
  • Jambes, Belgium, 5100
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Malmedy, Belgium, 4960
    • Research Site
  • Turnhout, Belgium, 2300
    • Research Site
  • Veurne, Belgium, 8630
    • Research Site
• Brazil
  • Fortaleza, Brazil, 60864190
    • Research Site
  • Porto Alegre, Brazil, 90610-000
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Research Site
  • Porto Alegre, Brazil, 90035-074
    • Research Site
  • Porto Alegre, Brazil, 90470-340
    • Research Site
  • Rio de Janeiro, Brazil, 22271-100
    • Research Site
  • Santo Andre, Brazil, 09080-110
    • Research Site
  • Sao Paulo, Brazil, 05403-000
    • Research Site
  • Sao Paulo, Brazil, 04023-062
    • Research Site
  • Sao Paulo, Brazil, 04020060
    • Research Site
  • Sorocaba, Brazil, 18040-425
    • Research Site
  • Vitória, Brazil, 29055-450
    • Research Site
• Bulgaria
  • Dupnitsa, Bulgaria, 2600
    • Research Site
  • Kozloduy, Bulgaria, 3320
    • Research Site
  • Pazardzhik, Bulgaria, 4400
    • Research Site
  • Pernik, Bulgaria, 2300
    • Research Site
  • Petrich, Bulgaria, 2850
    • Research Site
  • Plovdiv, Bulgaria, 4002
    • Research Site
  • Ruse, Bulgaria, 7002
    • Research Site
  • Sandanski, Bulgaria, 2800
    • Research Site
  • Silistra, Bulgaria
    • Research Site
  • Sofia, Bulgaria, 1002
    • Research Site
  • Sofia, Bulgaria, 1408
    • Research Site
  • Vidin, Bulgaria, 3700
    • Research Site
  • Vratsa, Bulgaria, 3000
    • Research Site
  • Yambol, Bulgaria, 8600
    • Research Site
• Chile
  • Curico, Chile, 3341643
    • Research Site
  • Quillota, Chile, 2260000
    • Research Site
  • Santiago, Chile, 7500698
    • Research Site
  • Santiago, Chile, 7500800
    • Research Site
  • Talca, Chile, 3465584
    • Research Site
• Colombia
  • Armenia, Colombia, 630004
    • Research Site
  • Barranquilla, Colombia, 80001
    • Research Site
  • Bogota, Colombia, 111511
    • Research Site
  • Bogotá, Colombia, 110221
    • Research Site
  • Bogotá, Colombia
    • Research Site
  • Cali, Colombia, 76001000
    • Research Site
  • Manizales, Colombia, 17001
    • Research Site
  • Medellin, Colombia, 5001000
    • Research Site
  • Medillin, Colombia
    • Research Site
• Croatia
  • Petrinja, Croatia, 44250
    • Research Site
• Denmark
  • Aarhus N, Denmark, 8200
    • Research Site
  • København NV, Denmark, 2400
    • Research Site
  • Næstved, Denmark, 4700
    • Research Site
  • Odense C, Denmark, 5000
    • Research Site
  • Roskilde, Denmark, 4000
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  • Silkeborg, Denmark, 8600
    • Research Site
• France
  • Bois Guillaume, France, 76031
    • Research Site
  • Brest Cedex, France, 29609
    • Research Site
  • La Tronche, France, 38700
    • Research Site
  • Lille cedex, France, 59037
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  • Lyon Cedex 04, France, 69317
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  • Marseille, France, 13915
    • Research Site
  • Montpellier, France, 34295
    • Research Site
  • NIMES Cedex 9, France, 30029
    • Research Site
  • Orléans Cedex 2, France, 45100
    • Research Site
  • Pessac, France, 33604
    • Research Site
• Israel
  • Haifa, Israel, 34362
    • Research Site
  • Jerusalem, Israel, 91120
    • Research Site
  • Jerusalem, Israel, 9372212
    • Research Site
  • Petach Tikva, Israel, 49100
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  • Rehovot, Israel, 7661041
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  • Tel Aviv, Israel, IL-
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• Mexico
  • Durango, Mexico, 43080
    • Research Site
  • Guadalajara, Mexico, 44130
    • Research Site
  • Guadalajara, Mexico, 44200
    • Research Site
  • Mexico, Mexico, 14050
    • Research Site
  • Monterrey, Mexico, 64460
    • Research Site
  • Monterrey, Mexico, 66465
    • Research Site
• New Zealand
  • Auckland, New Zealand, 2025
    • Research Site
  • Auckland, New Zealand, 0626
    • Research Site
  • Dunedin, New Zealand, 9016
    • Research Site
  • Greenlane, New Zealand, 1051
    • Research Site
  • Hamilton West, New Zealand, 3204
    • Research Site
  • Tauranga, New Zealand, 3112
    • Research Site
• Norway
  • Bodø, Norway, N-8092
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  • Kolbjørnsvik, Norway, N-4816
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  • Svelvik, Norway, 3060
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• Peru
  • Cusco, Peru, CUSCO 01
    • Research Site
  • Lima, Peru, 15033
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  • Lima, Peru, L27
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  • Lima, Peru, LIMA 1
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  • Lima, Peru, LIMA 31
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  • Lima, Peru, 41
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  • Lima, Peru, LIMA 33
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  • Lima, Peru, L41
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  • Lima, Peru, LIMA 21
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  • Piura, Peru
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• Philippines
  • Iloilo City, Philippines, 5000
    • Research Site
  • Lipa City, Philippines
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  • Manila, Philippines, 1000
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  • Quezon City, Philippines, 1101
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  • Quezon City, Philippines, 1100
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  • Quezon City, Philippines, 1109
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• Poland
  • Białystok, Poland, 15-044
    • Research Site
  • Białystok, Poland, 15-351
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  • Bydgoszcz, Poland, 85-231
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  • Gdańsk, Poland, 80-952
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  • Gorzów Wlkp, Poland, 66-400
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  • Grodzisk Mazowiecki, Poland, 05-825
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  • Karczew, Poland, 05-480
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  • Katowice, Poland, 40-648
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  • Kraków, Poland, 30-901
    • Research Site
  • Ostrowiec Świętokrzyski, Poland, 27-400
    • Research Site
  • Ostrów Wielkopolski, Poland, 63-400
    • Research Site
  • Ruda Śląska, Poland, 41-707
    • Research Site
  • Skierniewice, Poland, 96-100
    • Research Site
  • Sosnowiec, Poland, 41-200
    • Research Site
  • Starachowice, Poland, 27-200
    • Research Site
  • Szczecin, Poland, 70-111
    • Research Site
  • Słupca, Poland, 62-400
    • Research Site
  • Trzebnica, Poland, 55-100
    • Research Site
  • Wrocław, Poland, 53-301
    • Research Site
  • Wrocław, Poland, 51-162
    • Research Site
  • Żnin, Poland, 88-400
    • Research Site
• Serbia
  • Belgrade, Serbia, 11000
    • Research Site
• Slovenia
  • Celje, Slovenia, 3000
    • Research Site
  • Golnik, Slovenia, 4204
    • Research Site
  • Kamnik, Slovenia, 1241
    • Research Site
  • Ljubljana, Slovenia, 1000
    • Research Site
  • Maribor, Slovenia, 2000
    • Research Site
• Sweden
  • Goteborg, Sweden, 405 30
    • Research Site
  • Göteborg, Sweden, 41345
    • Research Site
  • Helsingborg, Sweden, 252 20
    • Research Site
  • Lund, Sweden, 221 85
    • Research Site
  • Malmo, Sweden, 21152
    • Research Site
  • Stockholm, Sweden, 114 46
    • Research Site
  • Uppsala, Sweden, 751 85
    • Research Site
• Taiwan
  • Changhua, Taiwan, 500
    • Research Site
  • Kaohsiung, Taiwan
    • Research Site
  • Kaohsiung, Taiwan, 83301
    • Research Site
  • New-Taipei, Taiwan, 22056
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Taichung, Taiwan, 40447
    • Research Site
  • Taipei, Taiwan
    • Research Site
  • Taipei, Taiwan, 112
    • Research Site
• Thailand
  • Bangkok, Thailand, 10600
    • Research Site
  • Bangkoknoi, Thailand, 10700
    • Research Site
  • Hat Yai, Thailand, 90110
    • Research Site
  • Khon Kaen, Thailand, 40002
    • Research Site
  • Muang,, Thailand, 55000
    • Research Site
  • Nonthaburi, Thailand, 11000
    • Research Site
• Turkey
  • Adana, Turkey, 01330
    • Research Site
  • Ankara, Turkey, 06280
    • Research Site
  • Bursa, Turkey, 16059
    • Research Site
  • Istanbul, Turkey, 34098
    • Research Site
  • Istanbul, Turkey, 34020
    • Research Site
  • Izmir, Turkey, 35100
    • Research Site
  • Izmir, Turkey, 35110
    • Research Site
  • Mersin, Turkey, 33343
    • Research Site
  • İstanbul, Turkey, 34844
    • Research Site
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Research Site
  • Chernivtsi, Ukraine, 58000
    • Research Site
  • Chernivtsi, Ukraine, 58022
    • Research Site
  • Dnipropetrovsk, Ukraine, 49051
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  • Ivano-Frankivsk, Ukraine, 76012
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  • Kharkiv, Ukraine, 61039
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  • Kharkiv, Ukraine, 61035
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  • Kyiv, Ukraine, 04107
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  • Kyiv, Ukraine, 03680
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  • Lutsk, Ukraine, 43000
    • Research Site
  • Lviv, Ukraine, 79066
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  • Odesa, Ukraine, 65025
    • Research Site
  • Vinnytsia, Ukraine, 21001
    • Research Site
  • Zaporizhzhya, Ukraine, 69068
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  • Zaporizhzhya, Ukraine, 69063
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  • Zaporizhzhya, Ukraine, 69065
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Research Site
    • Gulf Shores, Alabama, United States, 36542
      • Research Site
    • Montgomery, Alabama, United States, 36117
      • Research Site
  • Arizona
    • Flagstaff, Arizona, United States, 86001
      • Research Site
    • Phoenix, Arizona, United States, 85018
      • Research Site
  • California
    • Anaheim, California, United States, 92801
      • Research Site
    • Arcadia, California, United States, 91007
      • Research Site
    • Bakersfield, California, United States, 93301
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    • Fresno, California, United States, 93721
      • Research Site
    • Fullerton, California, United States, 92835
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    • Hawaiian Gardens, California, United States, 90716
      • Research Site
    • Huntington Beach, California, United States, 92647
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    • Los Angeles, California, United States, 90048
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    • Northridge, California, United States, 91324
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    • Palmdale, California, United States, 93551
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    • Peninsula, California, United States, 90505
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    • Placentia, California, United States, 92870
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    • Rolling Hills Estates, California, United States, 90274
      • Research Site
    • Westminster, California, United States, 92683
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  • Colorado
    • Centennial, Colorado, United States, 80112
      • Research Site
    • Colorado Springs, Colorado, United States, 80907
      • Research Site
    • Denver, Colorado, United States, 80246
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  • Florida
    • Chiefland, Florida, United States, 32626
      • Research Site
    • Clearwater, Florida, United States, 33765
      • Research Site
    • Clearwater, Florida, United States, 33759
      • Research Site
    • Coconut Creek, Florida, United States, 33066
      • Research Site
    • Coral Gables, Florida, United States, 33134
      • Research Site
    • Daytona Beach, Florida, United States, 32117
      • Research Site
    • DeBary, Florida, United States, 32713
      • Research Site
    • DeLand, Florida, United States, 32720
      • Research Site
    • Doral, Florida, United States, 33172
      • Research Site
    • Edgewater, Florida, United States, 32132
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    • Fort Lauderdale, Florida, United States, 33308
      • Research Site
    • Hialeah, Florida, United States, 33012
      • Research Site
    • Hialeah, Florida, United States, 33013
      • Research Site
    • Hialeah, Florida, United States, 33010
      • Research Site
    • Homestead, Florida, United States, 33130
      • Research Site
    • Jacksonville, Florida, United States, 32204
      • Research Site
    • Kissimmee, Florida, United States, 34744
      • Research Site
    • Miami, Florida, United States, 33126
      • Research Site
    • Miami, Florida, United States, 33186
      • Research Site
    • Miami, Florida, United States, 33165
      • Research Site
    • Miami, Florida, United States, 33144
      • Research Site
    • Miami, Florida, United States, 33155
      • Research Site
    • Miami, Florida, United States, 33174
      • Research Site
    • Miami, Florida, United States, 33147
      • Research Site
    • Pensacola, Florida, United States, 32504
      • Research Site
    • Port Charlotte, Florida, United States, 33952
      • Research Site
    • Sarasota, Florida, United States, 34239
      • Research Site
    • South Miami, Florida, United States, 33143
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Research Site
    • Blue Ridge, Georgia, United States, 30513
      • Research Site
    • Lawrenceville, Georgia, United States, 30046
      • Research Site
    • Woodstock, Georgia, United States, 30189
      • Research Site
  • Idaho
    • Nampa, Idaho, United States, 83687
      • Research Site
  • Illinois
    • Evergreen Park, Illinois, United States, 60805
      • Research Site
    • O'Fallon, Illinois, United States, 62269
      • Research Site
    • Peoria, Illinois, United States, 61602
      • Research Site
    • River Forest, Illinois, United States, 60305
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  • Kansas
    • Topeka, Kansas, United States, 66606
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  • Kentucky
    • Henderson, Kentucky, United States, 42420
      • Research Site
    • Owensboro, Kentucky, United States, 42303
      • Research Site
  • Louisiana
    • Opelousas, Louisiana, United States, 70570
      • Research Site
    • Shreveport, Louisiana, United States, 71106
      • Research Site
    • Sunset, Louisiana, United States, 70584
      • Research Site
  • Maine
    • Bangor, Maine, United States, 04401
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  • Maryland
    • Lutherville, Maryland, United States, 21093
      • Research Site
    • White Marsh, Maryland, United States, 21162
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  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Research Site
    • Marlborough, Massachusetts, United States, 01752
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  • Michigan
    • Buckley, Michigan, United States, 49620
      • Research Site
    • Kalamazoo, Michigan, United States, 49009
      • Research Site
    • Troy, Michigan, United States, 48085
      • Research Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Research Site
    • Fridley, Minnesota, United States, 55432
      • Research Site
    • Woodbury, Minnesota, United States, 55125
      • Research Site
  • Mississippi
    • Picayune, Mississippi, United States, 39466
      • Research Site
    • Port Gibson, Mississippi, United States, 39150
      • Research Site
  • Missouri
    • Belton, Missouri, United States, 64012
      • Research Site
    • Florissant, Missouri, United States, 63033
      • Research Site
    • Saint Louis, Missouri, United States, 63136
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  • Montana
    • Missoula, Montana, United States, 59808
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  • Nebraska
    • Fremont, Nebraska, United States, 68025
      • Research Site
    • Omaha, Nebraska, United States, 68124
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  • Nevada
    • Las Vegas, Nevada, United States, 89146
      • Research Site
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Research Site
    • Union, New Jersey, United States, 07083
      • Research Site
  • New York
    • Bronx, New York, United States, 10459
      • Research Site
    • Bronx, New York, United States, 10461
      • Research Site
    • Brooklyn, New York, United States, 11236
      • Research Site
    • Great Neck, New York, United States, 11023
      • Research Site
    • Mineola, New York, United States, 11501
      • Research Site
    • New Windsor, New York, United States, 12553
      • Research Site
    • New York, New York, United States, 10016
      • Research Site
    • Potsdam, New York, United States, 13676
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  • North Carolina
    • Burlington, North Carolina, United States, 27215
      • Research Site
    • Calabash, North Carolina, United States, 28467
      • Research Site
    • Charlotte, North Carolina, United States, 28277
      • Research Site
    • Hickory, North Carolina, United States, 28601
      • Research Site
    • Mooresville, North Carolina, United States, 28117
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    • New Bern, North Carolina, United States, 28562
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    • Shelby, North Carolina, United States, 28150
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  • Ohio
    • Chardon, Ohio, United States, 44024
      • Research Site
    • Cincinnati, Ohio, United States, 45242
      • Research Site
    • Columbus, Ohio, United States, 43213
      • Research Site
    • Columbus, Ohio, United States, 43214
      • Research Site
    • Marion, Ohio, United States, 43302
      • Research Site
    • Toledo, Ohio, United States, 43617
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  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Research Site
    • Oklahoma City, Oklahoma, United States, 73103
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  • Oregon
    • Clackamas, Oregon, United States, 97015-6804
      • Research Site
    • Medford, Oregon, United States, 97504
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  • Pennsylvania
    • Monroeville, Pennsylvania, United States, 15146
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19142
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    • Pittsburgh, Pennsylvania, United States, 15213
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15243
      • Research Site
    • Uniontown, Pennsylvania, United States, 15401
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  • South Carolina
    • Charleston, South Carolina, United States, 29412
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    • Hodges, South Carolina, United States, 29653
      • Research Site
    • Spartanburg, South Carolina, United States, 29303
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  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Research Site
  • Tennessee
    • Tullahoma, Tennessee, United States, 37388
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  • Texas
    • Corsicana, Texas, United States, 75110
      • Research Site
    • Dallas, Texas, United States, 75216
      • Research Site
    • Duncanville, Texas, United States, 75116
      • Research Site
    • Fort Worth, Texas, United States, 76104
      • Research Site
    • Houston, Texas, United States, 77034
      • Research Site
    • Houston, Texas, United States, 77024
      • Research Site
    • Houston, Texas, United States, 77055
      • Research Site
    • Houston, Texas, United States, 77043
      • Research Site
    • Houston, Texas, United States, 77036
      • Research Site
    • Houston, Texas, United States, 77063
      • Research Site
    • Houston, Texas, United States, 78756
      • Research Site
    • Huntsville, Texas, United States, 77340
      • Research Site
    • Killeen, Texas, United States, 76543
      • Research Site
    • Lampasas, Texas, United States, 76550
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    • Longview, Texas, United States, 75604
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    • Lufkin, Texas, United States, 75904
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    • McKinney, Texas, United States, 75069
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    • McKinney, Texas, United States, 75071
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    • Plano, Texas, United States, 75093
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    • Sealy, Texas, United States, 77474
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  • Utah
    • Bountiful, Utah, United States, 84010
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    • Salt Lake City, Utah, United States, 84102
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  • Virginia
    • Abingdon, Virginia, United States, 24210
      • Research Site
    • Richmond, Virginia, United States, 23220
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    • Richmond, Virginia, United States, 23235
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  • Washington
    • Everett, Washington, United States, 98208
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    • Tacoma, Washington, United States, 98405
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  • West Virginia
    • Kingwood, West Virginia, United States, 26357
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    • Morgantown, West Virginia, United States, 26505
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• Vietnam
  • Can Tho, Vietnam, 900000
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  • Hanoi, Vietnam, 100000
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  • Ho Chi Minh, Vietnam, 700000
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Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:.

• Informed consent.
• Subjects 40-85 y.o.

• Moderate to very severe COPD with Post Bronchodilator (BD) FEV1>20% and ≤65%.

  -≥2 moderate or ≥1 severe COPD exacerbation(s) required treatment or hospitalization within 2-52 weeks prior to Visit1.

• Modified Medical Research Council (mMRC) score ≥1 at Visit 1.
• Treatment with double or triple therapy throughout the year prior to Visit 1, constant 2 weeks prior to Visit 1.
• Tobacco history of ≥10 pack-years.
• Women of childbearing potential must use a highly effective form of birth control from Visit 1 until 16 weeks after their last dose, and negative serum pregnancy test result at Visit 1.
• Male subjects who are sexually active must be surgically sterile one year prior to Visit 1 or use an adequate method of contraception from the first Investigational Product (IP) dose until 16 weeks after their last dose.
• Compliance with maintenance therapy during run-in ≥70%.
• Blood eosinophils due to subject's stratification and cap for blood eosinophil levels.When any eosinophil cohort is full, subjects in the completed cohort will not be randomised and will be withdrawn from the study.

Exclusion criteria:

• Clinically important pulmonary disease other than COPD or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
• Any disorder or major physical impairment that is not stable by Investigator opinion and/or could affect: - subject safety-study findings or their interpretation or subject's ability to complete the entire study duration.
• Unstable ischemic heart disease, arrhythmia, cardiomyopathy, or other relevant cardiovascular disorder that in Investigator's judgment may put the patient at risk or negatively affect the study outcome.
• Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 2 weeks prior to Visit1 or during the enrolment and run-in period.
• Acute upper or lower respiratory infection requiring antibiotics within 2 weeks prior to Visit1 or during the enrolment and run-in period.
• Pneumonia within 8 weeks prior to Visit1 or during the enrolment and run-in period.
• Pregnant, breastfeeding, or lactating women.
• Risk factors for pneumonia
• History of anaphylaxis to any other biologic therapy.
• Long term oxygen therapy with signs and/or symptoms of cor pulmonale, right ventricular failure.
• Use of immunosuppressive medication within 2 weeks prior to Visit1 and/or during the enrolment and run-in period.
• Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to Visit 1.
• Evidence of active tuberculosis (TB) without an appropriate course of treatment.
• Lung volume reduction surgery within the 6 months prior to Visit 1. History of partial or total lung resection (single lobe or segmentectomy is acceptable).
• Asthma as a primary or main diagnosis according to the Global Initiative for Asthma (GINA) guidelines or other accepted guidelines.
• Previous treatment with benralizumab.
• Helminth parasitic infection diagnosed within 24 weeks prior to Visit 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo administered subcutaneously	Drug: Placebo; Benralizumab subcutaneously on study week 0 until study week 48 inclusive
Experimental: Benralizumab Arm A; Benralizumab administered subcutaneously	Drug: Benralizumab Arm A; Benralizumab subcutaneously on study week 0 until study week 48 inclusive
Experimental: Benralizumab Arm B; Benralizumab administered subcutaneously	Drug: Benralizumab Arm B; Benralizumab subcutaneously on study week 0 until study week 48 inclusive
Experimental: Benralizumab Arm C; Benralizumab administered subcutaneously	Drug: Benralizumab Arm C; Benralizumab subcutaneously on study week 0 until study week 48 inclusive

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL	A COPD exacerbation is defined by symptomatic worsening of COPD requiring: Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids; and/or; Use of antibiotics; and/or; An inpatient hospitalization or death due to COPD Annual COPD exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.	Immediately following the first IP dose through week 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline EOS>=220/uL	Pre-bronchodilator FEV1 (L) is collected at Weeks 0, 4, 8, 16, 24, 32, 40, 48, and 56. Baseline is the last non-missing value with quality (acceptable or borderline quality grade) prior to the first dose of study treatment.	First IP up to end of treatment Week 56
Mean Change From Baseline in SGRQ Total Score for Patients With Baseline EOS>=220/uL	SGRQ is from 50-item PRO instrument. The SGRQ total score is expressed as a percentage of overall impairment, in which 100% means the worst possible health status and 0 indicates the best possible health status.	First IP up to Week 56
Mean Change From Baseline in CAT Total Score for Patients With Baseline EOS>=220/uL	CAT is an 8-item PRO developed to measure the impact of COPD on health status. The instrument uses semantic differential six-point response scales. A CAT total score is the sum of item responses. Score ranges from 0 to 40 with higher scores indicative of greater COPD impact on health status.	First IP up to Week 56
Mean Change From Baseline in E-RS: COPD Total Score for Patients With Baseline EOS>=220/uL	The E-RS: COPD is an 11-item PRO developed to evaluate the severity of respiratory symptoms of COPD. Summation of E-RS: COPD item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity.	First IP up to Week 56
Mean Change From Baseline in Total Rescue Medication Use (Number of Puffs Per Day) for Patients With Baseline EOS>=220/uL	The number of rescue medication inhalations and nebulizer treatments taken are recorded by the patient in the eDiary twice daily. Total rescue medication use is the sum of daytime and night-time use.	First IP up to Week 56
Duration of Study Treatment Administration	Duration of study treatment is calculated from first dose date to last dose date + 1 day.	From first dose date to last dose date, 48 weeks per protocol.
Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS<220/uL	A COPD exacerbation is defined by symptomatic worsening of COPD requiring: Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids; and/or; Use of antibiotics; and/or; An inpatient hospitalization or death due to COPD Annual COPD exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.	Immediately following the first IP dose through week 56
Mean Change From Baseline in Proportion of Nights With Awakenings Due to Respiratory Symptoms for Patients With Baseline EOS>=220/uL	Change from baseline to Week 56 in proportion of nights with awakenings due to respiratory symptoms.	First IP up to Week 56
Number of Participants by Number of COPD Exacerbations Based on EXACT-PRO for Patients With Baseline EOS>=220/uL	The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while considering their experiences "today". The daily EXACT-PRO total score is recorded and has a range of 0-100 with higher scores indicative of greater severity. COPD exacerbation event frequency is calculated based on comparison of the baseline score with daily total scores. An increase of EXACT-PRO total score ≥9 for 3 days or ≥12 for 2 days indicates a COPD exacerbation event has occurred.	Immediately following first IP up to week 56
Severity of EXACT-PRO for Patients With Baseline EOS>=220/uL	The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while considering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. Severity of the study is the highest score of EXACT-PRO.	Immediately following first IP up to week 56
Duration of COPD Exacerbation Based on EXACT-PRO Score for Patients With Baseline EOS>=220/uL	The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while considering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. COPD exacerbation event frequency is identified by comparing the baseline score with daily total scores. An increase in EXACT-PRO total score ≥9 for 3 days or ≥12 for 2 days indicate an event has occurred. Event duration is calculated after identification of the following five parameters: 1) onset; 2) three-day rolling average; 3) maximum observed value; 4) threshold for improvement; and 5) recovery. That is, duration of the exacerbation is the time elapse between onset and recovery of the event.	Immediately following first IP up to week 56
Annual EXACT-PRO Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL	The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while considering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. Event frequency is calculated by comparing the baseline with daily total scores. An increase in EXACT-PRO total score ≥9 for 3 days or ≥12 for 2 days indicate an event has occurred. Annual EXACT-PRO exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.	Immediately following the first IP dose through week 56
Number of Participants Having at Least 1 COPD Exacerbation for Patients With Baseline EOS>=220/uL	A COPD exacerbation is defined by symptomatic worsening COPD requiring systemic corticosteroids, antibiotics, or an inpatient hospitalization/death due to COPD.	Immediately following first IP dose up to week 56
Time to First COPD Exacerbation	Time to first COPD exacerbation is from the randomization date to the first occurrence of COPD exacerbation.	Immediately following IP dose to Week 56
Annual COPD Exacerbation Rate Associated With ER or Hospitalization Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL	Annual COPD exacerbations rate that result in ER or hospitalization is calculated by number of exacerbations resulting ER or hospitalization divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.	Immediately following the first IP dose through week 56
Number of Participants Had COPD-related Healthcare Encounter for Patient With Baseline EOS>=220/uL	Types of healthcare encounter: Hospitalisations (inc. intensive care and/or general care), Emergency department visits, Unscheduled outpatients visits, Home visits, Telephone calls, and ambulance transports.	Immediately following first IP dose up to Week 56
Serum Concentration of Benralizumab	PK serum samples were collected pre-dose at each visit.	Pre-first dose and pre-dose at end of treatment (week 56).
Immunogenicity of Benralizumab	Anti-drug antibody (ADA) responses such as ADA prevalence, ADA incidence, ADA persistently positive counts, etc. were presented.	Pre-treatment until end of follow-up, week 60 per protocol.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: MedImmune LLC
• Investigators: Principal Investigator: Bartolome R. Celli, MD, Brigham and Women's Hospital, Pulmonary Division, 75 Francis Street, PBB Clinics 3, Boston, MA 02115

Publications and helpful links

General Publications

• Criner GJ, Celli BR, Singh D, Agusti A, Papi A, Jison M, Makulova N, Shih VH, Brooks L, Barker P, Martin UJ, Newbold P. Predicting response to benralizumab in chronic obstructive pulmonary disease: analyses of GALATHEA and TERRANOVA studies. Lancet Respir Med. 2020 Feb;8(2):158-170. doi: 10.1016/S2213-2600(19)30338-8. Epub 2019 Sep 28.
• Criner GJ, Celli BR, Brightling CE, Agusti A, Papi A, Singh D, Sin DD, Vogelmeier CF, Sciurba FC, Bafadhel M, Backer V, Kato M, Ramirez-Venegas A, Wei YF, Bjermer L, Shih VH, Jison M, O'Quinn S, Makulova N, Newbold P, Goldman M, Martin UJ; GALATHEA Study Investigators; TERRANOVA Study Investigators. Benralizumab for the Prevention of COPD Exacerbations. N Engl J Med. 2019 Sep 12;381(11):1023-1034. doi: 10.1056/NEJMoa1905248. Epub 2019 May 20.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2014
• Primary Completion (Actual): April 9, 2018
• Study Completion (Actual): April 9, 2018

Study Registration Dates

• First Submitted: May 20, 2014
• First Submitted That Met QC Criteria: June 2, 2014
• First Posted (Estimate): June 4, 2014

Study Record Updates

• Last Update Posted (Actual): June 26, 2019
• Last Update Submitted That Met QC Criteria: June 7, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Bronchial Diseases; Respiratory Tract Diseases; Obstructive Lung Diseases; Chronic Obstructive Pulmonary Disease; Lung Disease; COPD Exacerbation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Anti-Asthmatic Agents; Respiratory System Agents; Benralizumab
• Other Study ID Numbers: D3251C00004