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)

Hypercholesterolemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01507831
• Other study ID #: LTS11717
• Secondary ID: 2011-002806-59U1
• Status: Completed
• Phase: Phase 3
• First received: January 6, 2012
• Last updated: November 18, 2015
• Start date: January 2012
• Est. completion date: November 2014

Study information

• Verified date: November 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2341
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

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.
• Alirocumab
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a pre-filled syringe.
• Lipid-Modifying Therapy (LMT)
Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.

Locations

Country	Name	City	State
Argentina	Investigational Site Number 032006	Buenos Aires
Argentina	Investigational Site Number 032010	Caba
Argentina	Investigational Site Number 032008	Capital Federal
Argentina	Investigational Site Number 032001	Coronel Suarez
Argentina	Investigational Site Number 032004	Resistencia
Argentina	Investigational Site Number 032007	Zarate
Belgium	Investigational Site Number 056005	Antwerpen
Belgium	Investigational Site Number 056004	Genk
Belgium	Investigational Site Number 056001	Natoye
Belgium	Investigational Site Number 056002	Wetteren
Bulgaria	Investigational Site Number 100008	Pleven
Bulgaria	Investigational Site Number 100014	Plovdiv
Bulgaria	Investigational Site Number 100001	Sofia
Bulgaria	Investigational Site Number 100005	Sofia
Bulgaria	Investigational Site Number 100009	Sofia
Bulgaria	Investigational Site Number 100012	Sofia
Bulgaria	Investigational Site Number 100015	Sofia
Bulgaria	Investigational Site Number 100013	Stara Zagora
Bulgaria	Investigational Site Number 100007	Varna
Canada	Investigational Site Number 124013	Cambridge
Canada	Investigational Site Number 124027	Coquitlam
Canada	Investigational Site Number 124001	Hawkesbury
Canada	Investigational Site Number 124002	London
Canada	Investigational Site Number 124009	Mirabel
Canada	Investigational Site Number 124018	Montreal
Canada	Investigational Site Number 124007	Ottawa
Canada	Investigational Site Number 124011	Quebec
Canada	Investigational Site Number 124005	Saint John'S
Canada	Investigational Site Number 124008	Sarnia
Canada	Investigational Site Number 124022	Terrebonne
Canada	Investigational Site Number 124003	Vancouver
Canada	Investigational Site Number 124006	Victoria
Canada	Investigational Site Number 124015	Woodstock
Chile	Investigational Site Number 152007	Osorno
Chile	Investigational Site Number 152006	Santiago
Chile	Investigational Site Number 152008	Santiago
Chile	Investigational Site Number 152004	Temuco
Colombia	Investigational Site Number 170004	Barranquilla
Colombia	Investigational Site Number 170005	Barranquilla
Colombia	Investigational Site Number 170008	Barranquilla
Colombia	Investigational Site Number 170001	Manizales
Colombia	Investigational Site Number 170003	Medellin
Czech Republic	Investigational Site Number 203004	Praha 2
Czech Republic	Investigational Site Number 203006	Praha 5
Czech Republic	Investigational Site Number 203007	Praha 5
Denmark	Investigational Site Number 208005	Aarhus
Denmark	Investigational Site Number 208004	Hellerup
Denmark	Investigational Site Number 208003	Slagelse
Denmark	Investigational Site Number 208001	Svendborg
Denmark	Investigational Site Number 208002	Viborg
Finland	Investigational Site Number 246002	Joensuu
Finland	Investigational Site Number 246001	Kokkola
Finland	Investigational Site Number 246003	Kuopio
Finland	Investigational Site Number 246004	Vantaa
France	Investigational Site Number 250007	Bandol
France	Investigational Site Number 250003	Broglie
France	Investigational Site Number 250014	Bron Cedex
France	Investigational Site Number 250004	Dijon
France	Investigational Site Number 250006	Lille Cedex
France	Investigational Site Number 250001	Nantes
France	Investigational Site Number 250009	Nantes
France	Investigational Site Number 250002	Paris Cedex 13
France	Investigational Site Number 250010	Pessac
France	Investigational Site Number 250012	Rennes
France	Investigational Site Number 250005	Vieux Conde
France	Investigational Site Number 250008	Vihiers
Germany	Investigational Site Number 276001	Bad Wörishofen
Germany	Investigational Site Number 276005	Berlin
Germany	Investigational Site Number 276007	Berlin
Germany	Investigational Site Number 276014	Berlin
Germany	Investigational Site Number 276008	Bochum
Germany	Investigational Site Number 276009	Dresden
Germany	Investigational Site Number 276004	Essen
Germany	Investigational Site Number 276010	Frankfurt A.M.
Germany	Investigational Site Number 276011	Görlitz
Germany	Investigational Site Number 276019	Hannover
Germany	Investigational Site Number 276013	Leipzig
Germany	Investigational Site Number 276003	Magdeburg
Germany	Investigational Site Number 276012	Magdeburg
Germany	Investigational Site Number 276006	Schwerin
Germany	Investigational Site Number 276015	Witten
Hungary	Investigational Site Number 348003	Baja
Hungary	Investigational Site Number 348007	Budapest
Hungary	Investigational Site Number 348008	Budapest
Hungary	Investigational Site Number 348009	Budapest
Hungary	Investigational Site Number 348013	Budapest
Hungary	Investigational Site Number 348004	Debrecen
Hungary	Investigational Site Number 348002	Nagykanizsa
Hungary	Investigational Site Number 348006	Nyiregyhaza
Hungary	Investigational Site Number 348001	Sopron
Hungary	Investigational Site Number 348011	Urhida
Israel	Investigational Site Number 376002	Afula
Israel	Investigational Site Number 376003	Holon
Israel	Investigational Site Number 376005	Holon
Israel	Investigational Site Number 376004	Nazareth
Italy	Investigational Site Number 380006	Chieti
Italy	Investigational Site Number 380002	Cinisello Balsamo
Italy	Investigational Site Number 380009	Milano
Italy	Investigational Site Number 380007	Napoli
Italy	Investigational Site Number 380001	Palermo
Italy	Investigational Site Number 380005	Pozzilli
Italy	Investigational Site Number 380008	Vittorio Veneto
Italy	Investigational Site Number 380010	Zingonia-Osio Sotto
Mexico	Investigational Site Number 484010	Df
Mexico	Investigational Site Number 484004	Mexico
Mexico	Investigational Site Number 484008	Not Provided
Mexico	Investigational Site Number 484001	San Luis Potosi
Mexico	Investigational Site Number 484002	Tijuana
Mexico	Investigational Site Number 484009	Torreon
Mexico	Investigational Site Number 484003	Xalapa
Netherlands	Investigational Site Number 528001	Amsterdam
Netherlands	Investigational Site Number 528013	Amsterdam
Netherlands	Investigational Site Number 528004	Breda
Netherlands	Investigational Site Number 528005	Eindhoven
Netherlands	Investigational Site Number 528007	Groningen
Netherlands	Investigational Site Number 528011	Hoogeveen
Netherlands	Investigational Site Number 528002	Hoorn
Netherlands	Investigational Site Number 528008	Leiderdorp
Netherlands	Investigational Site Number 528009	Rotterdam
Netherlands	Investigational Site Number 528006	Velp
Netherlands	Investigational Site Number 528012	Venlo
Netherlands	Investigational Site Number 528010	Zoetermeer
Norway	Investigational Site Number 578005	Elverum
Norway	Investigational Site Number 578001	Hamar
Norway	Investigational Site Number 578002	Oslo
Norway	Investigational Site Number 578004	Skedsmokorset
Norway	Investigational Site Number 578003	Stavanger
Poland	Investigational Site Number 616003	Gdynia
Poland	Investigational Site Number 616008	Gdynia
Poland	Investigational Site Number 616001	Gniewkowo
Poland	Investigational Site Number 616010	Katowice
Poland	Investigational Site Number 616018	Krakow
Poland	Investigational Site Number 616004	Piotrkow Trybunalski
Poland	Investigational Site Number 616013	Pulawy
Poland	Investigational Site Number 616009	Warszawa
Poland	Investigational Site Number 616007	Wroclaw
Portugal	Investigational Site Number 620006	Funchal / Madeira
Portugal	Investigational Site Number 620001	Lisboa
Portugal	Investigational Site Number 620002	Lisboa
Portugal	Investigational Site Number 620005	Porto
Romania	Investigational Site Number 642005	Baia Mare
Romania	Investigational Site Number 642002	Brasov
Romania	Investigational Site Number 642004	Targu Mures
Romania	Investigational Site Number 642001	Timisoara
Russian Federation	Investigational Site Number 643005	Barnaul
Russian Federation	Investigational Site Number 643008	Moscow
Russian Federation	Investigational Site Number 643012	Moscow
Russian Federation	Investigational Site Number 643014	Perm
Russian Federation	Investigational Site Number 643006	St Petersburg
Russian Federation	Investigational Site Number 643009	St.Petersburg
Russian Federation	Investigational Site Number 643004	Yaroslavl
South Africa	Investigational Site Number 710010	Centurion
South Africa	Investigational Site Number 710008	Meyerspark
South Africa	Investigational Site Number 710011	Middelburg
South Africa	Investigational Site Number 710006	Parktown
South Africa	Investigational Site Number 710001	Pretoria
South Africa	Investigational Site Number 710002	Pretoria
South Africa	Investigational Site Number 710004	Pretoria
South Africa	Investigational Site Number 710009	Roodepoort
South Africa	Investigational Site Number 710003	Somerset West
South Africa	Investigational Site Number 710005	Witbank
South Africa	Investigational Site Number 710007	Worcester
Spain	Investigational Site Number 724006	Córdoba
Spain	Investigational Site Number 724003	Granada
Spain	Investigational Site Number 724002	Madrid
Spain	Investigational Site Number 724007	Málaga
Spain	Investigational Site Number 724008	Quart De Poblet
Spain	Investigational Site Number 724005	Reus
Spain	Investigational Site Number 724001	Sabadell
Spain	Investigational Site Number 724004	Sevilla
Sweden	Investigational Site Number 752001	Örebro
Sweden	Investigational Site Number 752002	Rättvik
Sweden	Investigational Site Number 752003	Stockholm
Sweden	Investigational Site Number 752004	Stockholm
Sweden	Investigational Site Number 752006	Stockholm
Ukraine	Investigational Site Number 804012	Chernivtsi
Ukraine	Investigational Site Number 804003	Dnipropetrovsk
Ukraine	Investigational Site Number 804002	Donetsk
Ukraine	Investigational Site Number 804014	Kharkiv
Ukraine	Investigational Site Number 804016	Kiev
Ukraine	Investigational Site Number 804001	Kyiv
Ukraine	Investigational Site Number 804008	Kyiv
Ukraine	Investigational Site Number 804010	Kyiv
Ukraine	Investigational Site Number 804011	Kyiv
Ukraine	Investigational Site Number 804013	Kyiv
Ukraine	Investigational Site Number 804005	Zhytomyr
United Kingdom	Investigational Site Number 826004	Addlestone
United Kingdom	Investigational Site Number 826009	Birmingham
United Kingdom	Investigational Site Number 826016	Birmingham
United Kingdom	Investigational Site Number 826021	Blackpool
United Kingdom	Investigational Site Number 826023	Cambridge
United Kingdom	Investigational Site Number 826012	Cardiff
United Kingdom	Investigational Site Number 826024	Chichester
United Kingdom	Investigational Site Number 826006	Chorley
United Kingdom	Investigational Site Number 826010	Glasgow
United Kingdom	Investigational Site Number 826003	Irvine
United Kingdom	Investigational Site Number 826005	Liverpool
United Kingdom	Investigational Site Number 826008	Liverpool
United Kingdom	Investigational Site Number 826007	Manchester
United Kingdom	Investigational Site Number 826025	Manchester
United Kingdom	Investigational Site Number 826001	Middlesex
United Kingdom	Investigational Site Number 826019	Penzance
United Kingdom	Investigational Site Number 826011	Reading
United Kingdom	Investigational Site Number 826013	Romford
United Kingdom	Investigational Site Number 826014	Soham
United States	Investigational Site Number 840217	Asheville	North Carolina
United States	Investigational Site Number 840150	Atlantis	Florida
United States	Investigational Site Number 840170	Beaver	Pennsylvania
United States	Investigational Site Number 840194	Beverly Hills	California
United States	Investigational Site Number 840209	Beverly Hills	California
United States	Investigational Site Number 840244	Biddeford	Maine
United States	Investigational Site Number 840020	Bradenton	Florida
United States	Investigational Site Number 840041	Brandon	Florida
United States	Investigational Site Number 840224	Bridgeport	Connecticut
United States	Investigational Site Number 840097	Bronxville	New York
United States	Investigational Site Number 840129	Brooklyn	New York
United States	Investigational Site Number 840180	Camp Hill	Pennsylvania
United States	Investigational Site Number 840073	Charleston	South Carolina
United States	Investigational Site Number 840023	Charlotte	North Carolina
United States	Investigational Site Number 840204	Chesapeake	Virginia
United States	Investigational Site Number 840068	Cincinnati	Ohio
United States	Investigational Site Number 840039	Clearwater	Florida
United States	Investigational Site Number 840184	Clearwater	Florida
United States	Investigational Site Number 840242	Clearwater	Florida
United States	Investigational Site Number 840086	Colorado Springs	Colorado
United States	Investigational Site Number 840182	Crystal River	Florida
United States	Investigational Site Number 840117	Cumming	Georgia
United States	Investigational Site Number 840092	Dallas	Texas
United States	Investigational Site Number 840212	Dallas	Texas
United States	Investigational Site Number 840007	Dayton	Ohio
United States	Investigational Site Number 840002	Daytona Beach	Florida
United States	Investigational Site Number 840166	Daytona Beach	Florida
United States	Investigational Site Number 840004	Duncansville	Pennsylvania
United States	Investigational Site Number 840022	Edison	New Jersey
United States	Investigational Site Number 840027	Evansville	Indiana
United States	Investigational Site Number 840167	Fleming Island	Florida
United States	Investigational Site Number 840018	Fort Lauderdale	Florida
United States	Investigational Site Number 840058	Fort Worth	Texas
United States	Investigational Site Number 840070	Fort Worth	Texas
United States	Investigational Site Number 840149	Fort Worth	Texas
United States	Investigational Site Number 840158	Framingham	Maine
United States	Investigational Site Number 840207	Fresno	California
United States	Investigational Site Number 840090	Ft. Lauderdale	Florida
United States	Investigational Site Number 840028	Gilbert	Arizona
United States	Investigational Site Number 840077	Golden	Colorado
United States	Investigational Site Number 840083	Greensboro	North Carolina
United States	Investigational Site Number 840087	Greenville	South Carolina
United States	Investigational Site Number 840134	Guilford	Connecticut
United States	Investigational Site Number 840246	Hartford	Connecticut
United States	Investigational Site Number 840095	Henderson	Nevada
United States	Investigational Site Number 840096	Henderson	Nevada
United States	Investigational Site Number 840011	Hillsborough	New Jersey
United States	Investigational Site Number 840038	Houston	Texas
United States	Investigational Site Number 840047	Houston	Texas
United States	Investigational Site Number 840159	Huntsville	Alabama
United States	Investigational Site Number 840093	Indianapolis	Indiana
United States	Investigational Site Number 840222	Iowa City	Iowa
United States	Investigational Site Number 840152	Jacksonville	Florida
United States	Investigational Site Number 840153	Jacksonville	Florida
United States	Investigational Site Number 840181	Jacksonville	Florida
United States	Investigational Site Number 840046	Jersey Shore	Pennsylvania
United States	Investigational Site Number 840200	Kansas City	Kansas
United States	Investigational Site Number 840190	Knoxville	Tennessee
United States	Investigational Site Number 840154	Lake Mary	Florida
United States	Investigational Site Number 840059	Largo	Florida
United States	Investigational Site Number 840101	Lincoln	California
United States	Investigational Site Number 840076	Long Beach	California
United States	Investigational Site Number 840013	Marion	Ohio
United States	Investigational Site Number 840161	Mentor	Ohio
United States	Investigational Site Number 840075	Meridian	Idaho
United States	Investigational Site Number 840221	Miami	Florida
United States	Investigational Site Number 840111	Milwaukee	Wisconsin
United States	Investigational Site Number 840021	New Port Richey	Florida
United States	Investigational Site Number 840122	New Smyrna Beach	Florida
United States	Investigational Site Number 840193	Novi	Michigan
United States	Investigational Site Number 840151	Ocala	Florida
United States	Investigational Site Number 840108	Ormond Beach	Florida
United States	Investigational Site Number 840067	Palm Harbor	Florida
United States	Investigational Site Number 840214	Pasadena	California
United States	Investigational Site Number 840006	Pembroke Pines	Florida
United States	Investigational Site Number 840155	Phoenixville	Pennsylvania
United States	Investigational Site Number 840053	Plano	Texas
United States	Investigational Site Number 840168	Ponte Vedra	Florida
United States	Investigational Site Number 840160	Poughkeepsie	New York
United States	Investigational Site Number 840104	Raleigh	North Carolina
United States	Investigational Site Number 840110	Roswell	Georgia
United States	Investigational Site Number 840045	Sacramento	California
United States	Investigational Site Number 840162	Saginaw	Michigan
United States	Investigational Site Number 840033	Saint Louis	Missouri
United States	Investigational Site Number 840031	Salt Lake City	Utah
United States	Investigational Site Number 840163	Santa Rosa	California
United States	Investigational Site Number 840164	Sarasota	Florida
United States	Investigational Site Number 840175	Sarasota	Florida
United States	Investigational Site Number 840026	Savannah	Georgia
United States	Investigational Site Number 840177	Scranton	Pennsylvania
United States	Investigational Site Number 840035	Sierra Vista	Arizona
United States	Investigational Site Number 840074	Simpsonville	South Carolina
United States	Investigational Site Number 840120	Spokane	Washington
United States	Investigational Site Number 840113	St. Louis	Missouri
United States	Investigational Site Number 840001	St. Petersburg	Florida
United States	Investigational Site Number 840003	St. Petersburg	Florida
United States	Investigational Site Number 840055	Stamford	Connecticut
United States	Investigational Site Number 840091	Stamford	Connecticut
United States	Investigational Site Number 840072	Sugar Land	Texas
United States	Investigational Site Number 840052	Tempe	Arizona
United States	Investigational Site Number 840065	Tempe	Arizona
United States	Investigational Site Number 840079	Tempe	Arizona
United States	Investigational Site Number 840094	Tempe	Arizona
United States	Investigational Site Number 840049	Trenton	New Jersey
United States	Investigational Site Number 840103	Tucson	Arizona
United States	Investigational Site Number 840005	Tulsa	Oklahoma
United States	Investigational Site Number 840241	Tyler	Texas
United States	Investigational Site Number 840105	Varnville	South Carolina
United States	Investigational Site Number 840165	West Des Moines	Iowa
United States	Investigational Site Number 840036	West Palm Beach	Florida
United States	Investigational Site Number 840032	Wichita	Kansas
United States	Investigational Site Number 840040	Wichita	Kansas
United States	Investigational Site Number 840061	Wichita	Kansas
United States	Investigational Site Number 840084	Wichita	Kansas
United States	Investigational Site Number 840202	Wyomissing	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Bulgaria,  Canada,  Chile,  Colombia,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Romania,  Russian Federation,  South Africa,  Spain,  Sweden,  Ukraine,  United Kingdom, 

References & Publications (1)

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 reducin — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Other	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)	Yes
Primary	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)	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No