Long-term Safety and Tolerability of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY Long Term)

Long-term Safety and Tolerability of SAR236553 (REGN727) in High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Lipid Modifying Therapy: A Randomized, Double-Blind, Placebo-Controlled Study

Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).

Primary Objective of the study:

To evaluate the long-term safety and tolerability of alirocumab in high cardiovascular risk participants with hypercholesterolemia not adequately controlled with their current lipid modifying therapy (LMT).

Secondary Objectives:

• To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 24 weeks of treatment in comparison with placebo.
• To evaluate the effect of alirocumab in comparison with placebo on LDL-C at other time points.
• To evaluate the effects of alirocumab on other lipid parameters.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Placebo (for alirocumab); Drug: Lipid-Modifying Therapy (LMT); Drug: Alirocumab

Detailed Description

The maximum study duration was to be 89 weeks per participant, including a 3-week screening period, a 78-week randomized treatment period and 8-week follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 2341
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425DES
    • Investigational Site Number 032006
  • Caba, Argentina, C1440AAD
    • Investigational Site Number 032010
  • Capital Federal, Argentina, 1119
    • Investigational Site Number 032008
  • Coronel Suarez, Argentina, B7540GHD
    • Investigational Site Number 032001
  • Resistencia, Argentina, H3500CDM
    • Investigational Site Number 032004
  • Zarate, Argentina, B2800DGH
    • Investigational Site Number 032007
• Belgium
  • Antwerpen, Belgium, 2020
    • Investigational Site Number 056005
  • Genk, Belgium, 3600
    • Investigational Site Number 056004
  • Natoye, Belgium, 5360
    • Investigational Site Number 056001
  • Wetteren, Belgium, 9230
    • Investigational Site Number 056002
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Investigational Site Number 100008
  • Plovdiv, Bulgaria, 4000
    • Investigational Site Number 100014
  • Sofia, Bulgaria, 1203
    • Investigational Site Number 100005
  • Sofia, Bulgaria, 1233
    • Investigational Site Number 100012
  • Sofia, Bulgaria, 1233
    • Investigational Site Number 100015
  • Sofia, Bulgaria, 1527
    • Investigational Site Number 100009
  • Sofia, Bulgaria, 1606
    • Investigational Site Number 100001
  • Stara Zagora, Bulgaria, 6000
    • Investigational Site Number 100013
  • Varna, Bulgaria, 9010
    • Investigational Site Number 100007
• Canada
  • Cambridge, Canada, N1R 6V6
    • Investigational Site Number 124013
  • Coquitlam, Canada, V3K 3P4
    • Investigational Site Number 124027
  • Hawkesbury, Canada, K6A 1A1
    • Investigational Site Number 124001
  • London, Canada, N5W 6A2
    • Investigational Site Number 124002
  • Mirabel, Canada, J7J 2K8
    • Investigational Site Number 124009
  • Montreal, Canada, H1T 3Y7
    • Investigational Site Number 124018
  • Ottawa, Canada, K1K 4L2
    • Investigational Site Number 124007
  • Quebec, Canada, G1V 4M6
    • Investigational Site Number 124011
  • Saint John'S, Canada, A1A 3R5
    • Investigational Site Number 124005
  • Sarnia, Canada, N7T 4X3
    • Investigational Site Number 124008
  • Terrebonne, Canada, J6V 1S8
    • Investigational Site Number 124022
  • Vancouver, Canada, V5Z 1M9
    • Investigational Site Number 124003
  • Victoria, Canada, V8T 5G4
    • Investigational Site Number 124006
  • Woodstock, Canada, N4S 5P5
    • Investigational Site Number 124015
• Chile
  • Osorno, Chile, 5311092
    • Investigational Site Number 152007
  • Santiago, Chile, 7980378
    • Investigational Site Number 152008
  • Santiago, Chile, 8053095
    • Investigational Site Number 152006
  • Temuco, Chile, 4790869
    • Investigational Site Number 152004
• Colombia
  • Barranquilla, Colombia
    • Investigational Site Number 170004
  • Barranquilla, Colombia
    • Investigational Site Number 170005
  • Barranquilla, Colombia
    • Investigational Site Number 170008
  • Manizales, Colombia
    • Investigational Site Number 170001
  • Medellin, Colombia
    • Investigational Site Number 170003
• Czech Republic
  • Praha 2, Czech Republic, 128 08
    • Investigational Site Number 203004
  • Praha 5, Czech Republic, 15006
    • Investigational Site Number 203007
  • Praha 5, Czech Republic, 15800
    • Investigational Site Number 203006
• Denmark
  • Aarhus, Denmark, 8200
    • Investigational Site Number 208005
  • Hellerup, Denmark, 2900
    • Investigational Site Number 208004
  • Slagelse, Denmark, 4200
    • Investigational Site Number 208003
  • Svendborg, Denmark, 5700
    • Investigational Site Number 208001
  • Viborg, Denmark, 8800
    • Investigational Site Number 208002
• Finland
  • Joensuu, Finland, 80100
    • Investigational Site Number 246002
  • Kokkola, Finland, 67100
    • Investigational Site Number 246001
  • Kuopio, Finland, 70210
    • Investigational Site Number 246003
  • Vantaa, Finland, 01600
    • Investigational Site Number 246004
• France
  • Bandol, France, 83150
    • Investigational Site Number 250007
  • Broglie, France, 27270
    • Investigational Site Number 250003
  • Bron Cedex, France, 69677
    • Investigational Site Number 250014
  • Dijon, France, 21000
    • Investigational Site Number 250004
  • Lille Cedex, France, 59037
    • Investigational Site Number 250006
  • Nantes, France, 44093
    • Investigational Site Number 250009
  • Nantes, France, 44300
    • Investigational Site Number 250001
  • Paris Cedex 13, France, 75651
    • Investigational Site Number 250002
  • Pessac, France, 33604
    • Investigational Site Number 250010
  • Rennes, France, 35033
    • Investigational Site Number 250012
  • Vieux Conde, France, 59690
    • Investigational Site Number 250005
  • Vihiers, France, 49310
    • Investigational Site Number 250008
• Germany
  • Bad Wörishofen, Germany, 86825
    • Investigational Site Number 276001
  • Berlin, Germany, 12627
    • Investigational Site Number 276007
  • Berlin, Germany, 13125
    • Investigational Site Number 276005
  • Berlin, Germany, 13158
    • Investigational Site Number 276014
  • Bochum, Germany, 44787
    • Investigational Site Number 276008
  • Dresden, Germany, 01067
    • Investigational Site Number 276009
  • Essen, Germany, 45355
    • Investigational Site Number 276004
  • Frankfurt A.M., Germany, 60596
    • Investigational Site Number 276010
  • Görlitz, Germany, 02826
    • Investigational Site Number 276011
  • Hannover, Germany, 30159
    • Investigational Site Number 276019
  • Leipzig, Germany, 04103
    • Investigational Site Number 276013
  • Magdeburg, Germany, 39120
    • Investigational Site Number 276003
  • Magdeburg, Germany, 39104
    • Investigational Site Number 276012
  • Schwerin, Germany, 19055
    • Investigational Site Number 276006
  • Witten, Germany, 58455
    • Investigational Site Number 276015
• Hungary
  • Baja, Hungary, 6500
    • Investigational Site Number 348003
  • Budapest, Hungary, 1036
    • Investigational Site Number 348007
  • Budapest, Hungary, 1036
    • Investigational Site Number 348009
  • Budapest, Hungary, 1135
    • Investigational Site Number 348008
  • Budapest, Hungary, 1136
    • Investigational Site Number 348013
  • Debrecen, Hungary, 4032
    • Investigational Site Number 348004
  • Nagykanizsa, Hungary, 8800
    • Investigational Site Number 348002
  • Nyiregyhaza, Hungary, 4400
    • Investigational Site Number 348006
  • Sopron, Hungary, 9400
    • Investigational Site Number 348001
  • Urhida, Hungary, 8142
    • Investigational Site Number 348011
• Israel
  • Afula, Israel, 18101
    • Investigational Site Number 376002
  • Holon, Israel, 58100
    • Investigational Site Number 376003
  • Holon, Israel, 58100
    • Investigational Site Number 376005
  • Nazareth, Israel, 16100
    • Investigational Site Number 376004
• Italy
  • Chieti, Italy, 66013
    • Investigational Site Number 380006
  • Cinisello Balsamo, Italy, 20092
    • Investigational Site Number 380002
  • Milano, Italy, 20138
    • Investigational Site Number 380009
  • Napoli, Italy, 80131
    • Investigational Site Number 380007
  • Palermo, Italy, 90127
    • Investigational Site Number 380001
  • Pozzilli, Italy, 86077
    • Investigational Site Number 380005
  • Vittorio Veneto, Italy, 31029
    • Investigational Site Number 380008
  • Zingonia-Osio Sotto, Italy
    • Investigational Site Number 380010
• Mexico
  • Df, Mexico, 03300
    • Investigational Site Number 484010
  • Mexico, Mexico, 06090
    • Investigational Site Number 484004
  • Not Provided, Mexico
    • Investigational Site Number 484008
  • San Luis Potosi, Mexico, 78200
    • Investigational Site Number 484001
  • Tijuana, Mexico, 22500
    • Investigational Site Number 484002
  • Torreon, Mexico, 27000
    • Investigational Site Number 484009
  • Xalapa, Mexico, 91020
    • Investigational Site Number 484003
• Netherlands
  • Amsterdam, Netherlands, 1091 AC
    • Investigational Site Number 528013
  • Amsterdam, Netherlands, 1105 AZ
    • Investigational Site Number 528001
  • Breda, Netherlands, 4811 SW
    • Investigational Site Number 528004
  • Eindhoven, Netherlands, 5616GB
    • Investigational Site Number 528005
  • Groningen, Netherlands, 9711 SG
    • Investigational Site Number 528007
  • Hoogeveen, Netherlands, 7909 AA
    • Investigational Site Number 528011
  • Hoorn, Netherlands, 1625 HV
    • Investigational Site Number 528002
  • Leiderdorp, Netherlands, 2352 RA
    • Investigational Site Number 528008
  • Rotterdam, Netherlands, 3021 HC
    • Investigational Site Number 528009
  • Velp, Netherlands, 6883 ES
    • Investigational Site Number 528006
  • Venlo, Netherlands, 5912 BL
    • Investigational Site Number 528012
  • Zoetermeer, Netherlands, 2724 EK
    • Investigational Site Number 528010
• Norway
  • Elverum, Norway, 2402
    • Investigational Site Number 578005
  • Hamar, Norway, 2317
    • Investigational Site Number 578001
  • Oslo, Norway
    • Investigational Site Number 578002
  • Skedsmokorset, Norway, 2020
    • Investigational Site Number 578004
  • Stavanger, Norway, 4005
    • Investigational Site Number 578003
• Poland
  • Gdynia, Poland, 81-384
    • Investigational Site Number 616008
  • Gdynia, Poland, 81423
    • Investigational Site Number 616003
  • Gniewkowo, Poland, 88-140
    • Investigational Site Number 616001
  • Katowice, Poland, 40-748
    • Investigational Site Number 616010
  • Krakow, Poland, 31-315
    • Investigational Site Number 616018
  • Piotrkow Trybunalski, Poland, 97-300
    • Investigational Site Number 616004
  • Pulawy, Poland, 24-100
    • Investigational Site Number 616013
  • Warszawa, Poland, 02-777
    • Investigational Site Number 616009
  • Wroclaw, Poland, 50-088
    • Investigational Site Number 616007
• Portugal
  • Funchal / Madeira, Portugal, 9050
    • Investigational Site Number 620006
  • Lisboa, Portugal, 1169-024
    • Investigational Site Number 620002
  • Lisboa, Portugal, 1549-008
    • Investigational Site Number 620001
  • Porto, Portugal, 4200-319
    • Investigational Site Number 620005
• Romania
  • Baia Mare, Romania, 430031
    • Investigational Site Number 642005
  • Brasov, Romania, 500283
    • Investigational Site Number 642002
  • Targu Mures, Romania, 540099
    • Investigational Site Number 642004
  • Timisoara, Romania, 300358
    • Investigational Site Number 642001
• Russian Federation
  • Barnaul, Russian Federation
    • Investigational Site Number 643005
  • Moscow, Russian Federation, 119415
    • Investigational Site Number 643012
  • Moscow, Russian Federation, 125284
    • Investigational Site Number 643008
  • Perm, Russian Federation, 614097
    • Investigational Site Number 643014
  • St Petersburg, Russian Federation, 196084
    • Investigational Site Number 643006
  • St.Petersburg, Russian Federation, 196084
    • Investigational Site Number 643009
  • Yaroslavl, Russian Federation, 150002
    • Investigational Site Number 643004
• South Africa
  • Centurion, South Africa, 0158
    • Investigational Site Number 710010
  • Meyerspark, South Africa, 0184
    • Investigational Site Number 710008
  • Middelburg, South Africa, 1055
    • Investigational Site Number 710011
  • Parktown, South Africa, 2193
    • Investigational Site Number 710006
  • Pretoria, South Africa, 181
    • Investigational Site Number 710002
  • Pretoria, South Africa, 0002
    • Investigational Site Number 710004
  • Pretoria, South Africa, 0084
    • Investigational Site Number 710001
  • Roodepoort, South Africa, 1724
    • Investigational Site Number 710009
  • Somerset West, South Africa, 7130
    • Investigational Site Number 710003
  • Witbank, South Africa
    • Investigational Site Number 710005
  • Worcester, South Africa, 6850
    • Investigational Site Number 710007
• Spain
  • Córdoba, Spain, 14004
    • Investigational Site Number 724006
  • Granada, Spain, 18012
    • Investigational Site Number 724003
  • Madrid, Spain, 28040
    • Investigational Site Number 724002
  • Málaga, Spain, 29010
    • Investigational Site Number 724007
  • Quart De Poblet, Spain, 46930
    • Investigational Site Number 724008
  • Reus, Spain, 43201
    • Investigational Site Number 724005
  • Sabadell, Spain, 08208
    • Investigational Site Number 724001
  • Sevilla, Spain, 41013
    • Investigational Site Number 724004
• Sweden
  • Rättvik, Sweden, 79530
    • Investigational Site Number 752002
  • Stockholm, Sweden, 111 57
    • Investigational Site Number 752003
  • Stockholm, Sweden, 111 35
    • Investigational Site Number 752006
  • Stockholm, Sweden, 14186
    • Investigational Site Number 752004
  • Örebro, Sweden, 70146
    • Investigational Site Number 752001
• Ukraine
  • Chernivtsi, Ukraine, 58013
    • Investigational Site Number 804012
  • Dnipropetrovsk, Ukraine, 49006
    • Investigational Site Number 804003
  • Donetsk, Ukraine, 83114
    • Investigational Site Number 804002
  • Kharkiv, Ukraine, 61002
    • Investigational Site Number 804014
  • Kiev, Ukraine, 02091
    • Investigational Site Number 804016
  • Kyiv, Ukraine, 01103
    • Investigational Site Number 804011
  • Kyiv, Ukraine, 03115
    • Investigational Site Number 804010
  • Kyiv, Ukraine, 03680
    • Investigational Site Number 804001
  • Kyiv, Ukraine, 04053
    • Investigational Site Number 804008
  • Kyiv, Ukraine
    • Investigational Site Number 804013
  • Zhytomyr, Ukraine, 10002
    • Investigational Site Number 804005
• United Kingdom
  • Addlestone, United Kingdom, KT15 2BH
    • Investigational Site Number 826004
  • Birmingham, United Kingdom, B15 2SQ
    • Investigational Site Number 826009
  • Birmingham, United Kingdom, B18 7QH
    • Investigational Site Number 826016
  • Blackpool, United Kingdom, FY3 7EN
    • Investigational Site Number 826021
  • Cambridge, United Kingdom, CB2 OQQ
    • Investigational Site Number 826023
  • Cardiff, United Kingdom, CF14 5GJ
    • Investigational Site Number 826012
  • Chichester, United Kingdom, PO19 4SE
    • Investigational Site Number 826024
  • Chorley, United Kingdom, PR7 7NA
    • Investigational Site Number 826006
  • Glasgow, United Kingdom, G20 0SP
    • Investigational Site Number 826010
  • Irvine, United Kingdom, KA12 0AY
    • Investigational Site Number 826003
  • Liverpool, United Kingdom, L22 0LG
    • Investigational Site Number 826008
  • Liverpool, United Kingdom, L7 8XP
    • Investigational Site Number 826005
  • Manchester, United Kingdom, M13 9WL
    • Investigational Site Number 826025
  • Manchester, United Kingdom, M15 6SX
    • Investigational Site Number 826007
  • Middlesex, United Kingdom, HA6 2RN
    • Investigational Site Number 826001
  • Penzance, United Kingdom, TR19 7HH
    • Investigational Site Number 826019
  • Reading, United Kingdom, RG2 7AG
    • Investigational Site Number 826011
  • Romford, United Kingdom, RM7 0AG
    • Investigational Site Number 826013
  • Soham, United Kingdom, CB7 5JD
    • Investigational Site Number 826014
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Investigational Site Number 840159
  • Arizona
    • Gilbert, Arizona, United States, 85295
      • Investigational Site Number 840028
    • Sierra Vista, Arizona, United States, 85635
      • Investigational Site Number 840035
    • Tempe, Arizona, United States, 85282
      • Investigational Site Number 840052
    • Tempe, Arizona, United States, 85282
      • Investigational Site Number 840065
    • Tempe, Arizona, United States, 85282
      • Investigational Site Number 840079
    • Tempe, Arizona, United States, 85282
      • Investigational Site Number 840094
    • Tucson, Arizona, United States, 85741-3565
      • Investigational Site Number 840103
  • California
    • Beverly Hills, California, United States, 90210
      • Investigational Site Number 840209
    • Beverly Hills, California, United States, 90211
      • Investigational Site Number 840194
    • Fresno, California, United States, 93720
      • Investigational Site Number 840207
    • Lincoln, California, United States, 95648
      • Investigational Site Number 840101
    • Long Beach, California, United States, 90807
      • Investigational Site Number 840076
    • Pasadena, California, United States, 91105
      • Investigational Site Number 840214
    • Sacramento, California, United States, 95842
      • Investigational Site Number 840045
    • Santa Rosa, California, United States, 95405
      • Investigational Site Number 840163
  • Colorado
    • Colorado Springs, Colorado, United States, 80906
      • Investigational Site Number 840086
    • Golden, Colorado, United States, 80401
      • Investigational Site Number 840077
  • Connecticut
    • Bridgeport, Connecticut, United States, 06610
      • Investigational Site Number 840224
    • Guilford, Connecticut, United States, 06437
      • Investigational Site Number 840134
    • Hartford, Connecticut, United States, 06102
      • Investigational Site Number 840246
    • Stamford, Connecticut, United States, 06905
      • Investigational Site Number 840055
    • Stamford, Connecticut, United States, 06905
      • Investigational Site Number 840091
  • Florida
    • Atlantis, Florida, United States, 33462
      • Investigational Site Number 840150
    • Bradenton, Florida, United States, 34208
      • Investigational Site Number 840020
    • Brandon, Florida, United States, 33511
      • Investigational Site Number 840041
    • Clearwater, Florida, United States, 33756
      • Investigational Site Number 840184
    • Clearwater, Florida, United States, 33756
      • Investigational Site Number 840242
    • Clearwater, Florida, United States, 33765
      • Investigational Site Number 840039
    • Crystal River, Florida, United States, 34429
      • Investigational Site Number 840182
    • Daytona Beach, Florida, United States, 32117
      • Investigational Site Number 840002
    • Daytona Beach, Florida, United States, 32117
      • Investigational Site Number 840166
    • Fleming Island, Florida, United States, 32003
      • Investigational Site Number 840167
    • Fort Lauderdale, Florida, United States, 33309
      • Investigational Site Number 840018
    • Ft. Lauderdale, Florida, United States, 33308
      • Investigational Site Number 840090
    • Jacksonville, Florida, United States, 32204
      • Investigational Site Number 840153
    • Jacksonville, Florida, United States, 32205
      • Investigational Site Number 840181
    • Jacksonville, Florida, United States, 32216
      • Investigational Site Number 840152
    • Lake Mary, Florida, United States, 32746
      • Investigational Site Number 840154
    • Largo, Florida, United States, 33773
      • Investigational Site Number 840059
    • Miami, Florida, United States, 33176
      • Investigational Site Number 840221
    • New Port Richey, Florida, United States, 34652
      • Investigational Site Number 840021
    • New Smyrna Beach, Florida, United States, 32169
      • Investigational Site Number 840122
    • Ocala, Florida, United States, 34471
      • Investigational Site Number 840151
    • Ormond Beach, Florida, United States, 32174
      • Investigational Site Number 840108
    • Palm Harbor, Florida, United States, 34684
      • Investigational Site Number 840067
    • Pembroke Pines, Florida, United States, 33026
      • Investigational Site Number 840006
    • Ponte Vedra, Florida, United States, 32081
      • Investigational Site Number 840168
    • Sarasota, Florida, United States, 34239
      • Investigational Site Number 840164
    • Sarasota, Florida, United States, 34239
      • Investigational Site Number 840175
    • St. Petersburg, Florida, United States
      • Investigational Site Number 840001
    • St. Petersburg, Florida, United States
      • Investigational Site Number 840003
    • West Palm Beach, Florida, United States, 33401
      • Investigational Site Number 840036
  • Georgia
    • Cumming, Georgia, United States, 30041
      • Investigational Site Number 840117
    • Roswell, Georgia, United States, 30076
      • Investigational Site Number 840110
    • Savannah, Georgia, United States, 31405
      • Investigational Site Number 840026
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Investigational Site Number 840075
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Investigational Site Number 840027
    • Indianapolis, Indiana, United States, 46260
      • Investigational Site Number 840093
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Investigational Site Number 840222
    • West Des Moines, Iowa, United States, 50266
      • Investigational Site Number 840165
  • Kansas
    • Kansas City, Kansas, United States, 66160-7321
      • Investigational Site Number 840200
    • Wichita, Kansas, United States, 67203
      • Investigational Site Number 840040
    • Wichita, Kansas, United States, 67205
      • Investigational Site Number 840061
    • Wichita, Kansas, United States, 67207
      • Investigational Site Number 840032
    • Wichita, Kansas, United States, 67207
      • Investigational Site Number 840084
  • Maine
    • Biddeford, Maine, United States, 04005
      • Investigational Site Number 840244
    • Framingham, Maine, United States, 01702
      • Investigational Site Number 840158
  • Michigan
    • Novi, Michigan, United States, 48374
      • Investigational Site Number 840193
    • Saginaw, Michigan, United States, 48604
      • Investigational Site Number 840162
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Investigational Site Number 840033
    • St. Louis, Missouri, United States, 63131
      • Investigational Site Number 840113
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Investigational Site Number 840095
    • Henderson, Nevada, United States, 89052
      • Investigational Site Number 840096
  • New Jersey
    • Edison, New Jersey, United States, 08817
      • Investigational Site Number 840022
    • Hillsborough, New Jersey, United States, 08844
      • Investigational Site Number 840011
    • Trenton, New Jersey, United States, 08611
      • Investigational Site Number 840049
  • New York
    • Bronxville, New York, United States, 10708
      • Investigational Site Number 840097
    • Brooklyn, New York, United States, 11215
      • Investigational Site Number 840129
    • Poughkeepsie, New York, United States, 12601
      • Investigational Site Number 840160
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Investigational Site Number 840217
    • Charlotte, North Carolina, United States, 28211
      • Investigational Site Number 840023
    • Greensboro, North Carolina, United States, 27408
      • Investigational Site Number 840083
    • Raleigh, North Carolina, United States, 27609
      • Investigational Site Number 840104
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Investigational Site Number 840068
    • Dayton, Ohio, United States, 45406
      • Investigational Site Number 840007
    • Marion, Ohio, United States, 43302
      • Investigational Site Number 840013
    • Mentor, Ohio, United States, 44060
      • Investigational Site Number 840161
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Investigational Site Number 840005
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • Investigational Site Number 840170
    • Camp Hill, Pennsylvania, United States, 17011
      • Investigational Site Number 840180
    • Duncansville, Pennsylvania, United States, 16635
      • Investigational Site Number 840004
    • Jersey Shore, Pennsylvania, United States, 17740
      • Investigational Site Number 840046
    • Phoenixville, Pennsylvania, United States, 19460
      • Investigational Site Number 840155
    • Scranton, Pennsylvania, United States, 18508
      • Investigational Site Number 840177
    • Wyomissing, Pennsylvania, United States, 19610
      • Investigational Site Number 840202
  • South Carolina
    • Charleston, South Carolina, United States, 29485
      • Investigational Site Number 840073
    • Greenville, South Carolina, United States, 29615
      • Investigational Site Number 840087
    • Simpsonville, South Carolina, United States, 29681
      • Investigational Site Number 840074
    • Varnville, South Carolina, United States, 29944
      • Investigational Site Number 840105
  • Tennessee
    • Knoxville, Tennessee, United States, 37917
      • Investigational Site Number 840190
  • Texas
    • Dallas, Texas, United States, 75216
      • Investigational Site Number 840092
    • Dallas, Texas, United States, 75226
      • Investigational Site Number 840212
    • Fort Worth, Texas, United States, 76104
      • Investigational Site Number 840058
    • Fort Worth, Texas, United States, 76104
      • Investigational Site Number 840149
    • Fort Worth, Texas, United States, 76117
      • Investigational Site Number 840070
    • Houston, Texas, United States, 77024
      • Investigational Site Number 840038
    • Houston, Texas, United States, 77074
      • Investigational Site Number 840047
    • Plano, Texas, United States, 75023
      • Investigational Site Number 840053
    • Sugar Land, Texas, United States, 77479
      • Investigational Site Number 840072
    • Tyler, Texas, United States, 75701
      • Investigational Site Number 840241
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Investigational Site Number 840031
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Investigational Site Number 840204
  • Washington
    • Spokane, Washington, United States, 99204
      • Investigational Site Number 840120
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209-0996
      • Investigational Site Number 840111

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

Either A or B below and who were not adequately controlled with their lipid-modifying therapy:

A) Participants with heterozygous familial hypercholesterolemia (heFH) with or without established coronary heart disease (CHD) or CHD risk equivalents

OR

B) Participants with hypercholesterolemia together with established CHD or CHD risk equivalents.

Exclusion criteria:

• Age < 18 years
• LDL-C <70 mg/dL (< 1.81 mmol/L)
• Fasting serum triglycerides > 400 mg/dL (>4.52 mmol/L)

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo (for alirocumab) every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 78 weeks.	Drug: Placebo (for alirocumab); Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a pre-filled syringe.; Drug: Lipid-Modifying Therapy (LMT); Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.
Experimental: Alirocumab; Alirocumab 150 mg Q2W added to stable LMT for 78 weeks.	Drug: Lipid-Modifying Therapy (LMT); Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.; Drug: Alirocumab; Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a pre-filled syringe.; Other Names: SAR236553; REGN727; Praluent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced Adverse Events (AEs)	Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	Up to 10 weeks after last study drug administration (maximum of 86 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.	From Baseline to Week 52
Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis	Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).	From Baseline to Week 52
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.	From Baseline to Week 52
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis	Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.	From Baseline to Week 52
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis	Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.	From Baseline to Week 52
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis	Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.	From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis	Adjusted least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were used in the model (ITT analysis).	From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection) (on-treatment analysis).	From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.	From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).	From Baseline to Week 52
Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis	Measured LDL-C values via beta quantification method. Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.	From Baseline to Week 52
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.	From Baseline to Week 52
Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).	From Baseline to Week 52
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.	From Baseline to Week 52
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.	From Baseline to Week 52
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.	From Baseline to Week 52
Percentage of Very High Cardiovascular (CV) Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis	Very high CV risk: Heterozygous Familial Hypercholesterolemia (heFH) participants with coronary heart disease (CHD) or CHD risk equivalents or non- Familial Hypercholesterolemia (FH). High CV risk: heFH participants without CHD or CHD risk equivalents. CHD risk equivalent: peripheral arterial disease, ischemic stroke, moderate chronic kidney disease (estimated glomerular filtration rate, 30 to <60 ml/minute/1.73 m^2 of body-surface area), or diabetes mellitus plus 2 or more additional risk factors (hypertension; ankle-brachial index of ≤0.90; microalbuminuria, macroalbuminuria, or a urinary dipstick result of >2+ protein; preproliferative or proliferative retinopathy or laser treatment for retinopathy; or family history of premature CHD). Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were included in imputation model.	Up to Week 52
Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis	Adjusted percentages at Week 24 were from multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).	Up to Week 52
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis	Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were included in the imputation model.	Up to Week 52
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis	Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 52 (i.e. up to 21 days after last injection).	Up to Week 52
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis	Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment were included in the imputation model.	From Baseline to Week 52
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.	From Baseline to Week 52
Percent Change From Baseline in Apo A1 at Week 24 - ITT Analysis	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.	From Baseline to Week 52
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.	From Baseline to Week 52
Percent Change From Baseline in Apo A1 at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.	From Baseline to Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Calculated LDL-C at Week 78 - ITT Analysis	Adjusted LS means and standard errors at Week 78 from MMRM model including all available post-baseline data from Week 4 to Week 78 regardless of status on- or off-treatment.	From Baseline to Week 78
Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis	Adjusted LS means and standard errors at Week 52 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.	From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis	Adjusted LS means and standard errors at Week 52 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).	From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 78 - On-Treatment Analysis	Adjusted LS means and standard errors at Week 78 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 78 (i.e. up to 21 days after last injection).	From Baseline to Week 78
Percentage of Participants Who Experienced Cardiovascular (CV) Events	CV events included coronary heart disease (CHD) death; non-fatal myocardial infarction (MI); fatal and non-fatal ischemic stroke; unstable angina requiring hospitalization; congestive heart failure (CHF) requiring hospitalization; ischemia-driven coronary revascularization procedure. Reported events are CV events as confirmed by an independent Clinical Events Committee (CEC) that occurred during the treatment emergent period ( i.e. from first dose up to the last dose of study drug + 70 days).	Up to 10 weeks after last study drug administration (maximum of 86 weeks)

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Mahmood T, Minnier J, Ito MK, Li QH, Koren A, Kam IW, Fazio S, Shapiro MD. Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies. Eur J Prev Cardiol. 2021 Jul 23;28(8):816-822. doi: 10.1177/2047487320915803. Epub 2020 Apr 10.
• Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.
• Defesche JC, Stefanutti C, Langslet G, Hopkins PN, Seiz W, Baccara-Dinet MT, Hamon SC, Banerjee P, Kastelein JJP. Efficacy of alirocumab in 1191 patients with a wide spectrum of mutations in genes causative for familial hypercholesterolemia. J Clin Lipidol. 2017 Nov-Dec;11(6):1338-1346.e7. doi: 10.1016/j.jacl.2017.08.016. Epub 2017 Sep 4. Erratum In: J Clin Lipidol. 2020 Sep - Oct;14(5):742.
• Kastelein JJ, Hovingh GK, Langslet G, Baccara-Dinet MT, Gipe DA, Chaudhari U, Zhao J, Minini P, Farnier M. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody alirocumab vs placebo in patients with heterozygous familial hypercholesterolemia. J Clin Lipidol. 2017 Jan-Feb;11(1):195-203.e4. doi: 10.1016/j.jacl.2016.12.004. Epub 2016 Dec 28.
• Ray KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, Eckel RH, Cannon CP. Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation. 2016 Dec 13;134(24):1931-1943. doi: 10.1161/CIRCULATIONAHA.116.024604. Epub 2016 Oct 24.
• Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, Stroes ES, Langslet G, Raal FJ, El Shahawy M, Koren MJ, Lepor NE, Lorenzato C, Pordy R, Chaudhari U, Kastelein JJ; ODYSSEY LONG TERM Investigators. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015 Apr 16;372(16):1489-99. doi: 10.1056/NEJMoa1501031. Epub 2015 Mar 15.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: January 6, 2012
• First Submitted That Met QC Criteria: January 10, 2012
• First Posted (Estimate): January 11, 2012

Study Record Updates

• Last Update Posted (Estimate): December 22, 2015
• Last Update Submitted That Met QC Criteria: November 18, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: LTS11717; 2011-002806-59 (EudraCT Number); U1111-1121-3928 (Other Identifier: UTN)