Trial to Assess the Effect of Long Term Dosing of Inclisiran in Subjects With High CV Risk and Elevated LDL-C
NCT ID: NCT03814187
Last Updated: 2024-03-06
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
3275 participants
INTERVENTIONAL
2019-04-16
2023-02-13
Brief Summary
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Detailed Description
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The End of Study (EOS) visit in the previous feeder studies was Day 1 in this extension study.The duration that each subject participated in this study was a maximum of 3 years. However, for subjects from the Study ORION-3, the Sponsor decided to end the study prior to completion of their full 3-year of participation. It is recorded in the database as discontinuation was due to Sponsor's decision.
In this Phase III extension study, the same study drug of inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) was administered as a single subcutaneous (SC) dose every 180 days from the last dose in previous feeder study (except for subjects newly initiating inclisiran, who received the first two doses 90 days apart) until the end of the study.
On Day 1 (EOS visit in the feeder study), subjects from the previous feeder studies received blinded study medication except subjects from Study ORION-3. Subjects who received placebo in the previous Phase III feeder study received blinded inclisiran and subjects who received inclisiran in the previous feeder study received blinded placebo at this visit, so that subjects previously on placebo received the correct dosing regime, i.e. a dose at Day 1, Day 90 and every 180-days thereafter. Subjects previously treated with inclisiran did not need a dose of inclisiran to maintain every 180-dosing regime and therefore, were given placebo in order to maintain the blinding of the feeder study. Subjects that moved over from ORION-3 received the first study medication at Day 90, as this study was already open-label.
On Day 90, all subjects received inclisiran sodium 300 mg. This is 180 days after the last injection in the previous feeder study for subjects that received inclisiran and was the second dose of inclisiran for the subjects that received placebo in the feeder study. The EOS visit occurred at Day 1080.
This extension study allowed subjects continued access to inclisiran treatment and allowed the collection of additional efficacy and safety data for long-term use beyond the end of the feeder studies.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Inclisiran
Inclisiran sodium 300 milligrams (mg) was administered as a single SC injection on Day 1\*, 90, then every 180 days to Day 990.
\*Subjects who received blinded placebo in the feeder study received blinded inclisiran and subjects who received blinded inclisiran in the feeder study received blinded placebo on Day 1 in ORION-8. Subjects from the open label ORION-3 study did not receive any injection of study drug on Day 1. Their first dose of study medication was at day 90
Inclisiran Sodium
Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
Interventions
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Inclisiran Sodium
Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
Eligibility Criteria
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Inclusion Criteria
2. On current lipid-lowering therapies (such as a statin and/or ezetimibe) from previous study with no planned medication or dose change during study participation.
3. Willing and able to give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures.
Exclusion Criteria
2. An underlying known disease, or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate) might interfere with interpretation of the clinical study results.
3. Severe concomitant noncardiovascular disease that carries the risk of reducing life expectancy to less than 3 years,
4. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST), elevation \>3x the upper limit of normal (ULN), or total bilirubin (TBIL) elevation \>2x ULN at the last recorded visit in the feeder study prior to study entry visit.
5. Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least one method of acceptable effective contraception (eg, oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device) for the entire duration of the study. Exemptions from this criterion:
1. Women \>2 years postmenopausal (defined as 1 year or longer since last menstrual period) and more than 55 years of age.
2. Postmenopausal women (as defined above) and less than 55 years of age with a negative pregnancy test within 24 hours of randomization.
3. Women who are surgically sterilized at least 3 months prior to enrollment.
6. Planned use of other investigational medicinal products other than inclisiran or devices during the course of the study.
7. Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to:
1. Subjects who are unable to communicate or to cooperate with the investigator
2. Unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study (including subjects whose cooperation is doubtful due to drug abuse or alcohol dependency)
3. Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (eg, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study)
4. Have any medical or surgical condition, which in the opinion of the investigator would put the subject at increased risk from participating in the study
5. Persons directly involved in the conduct of the study.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
18 Years
ALL
No
Sponsors
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Novartis Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Scott Wright, MD
Role: PRINCIPAL_INVESTIGATOR
Mayo Clinic
Locations
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Research Site 10001-015
Birmingham, Alabama, United States
Research Site 10001-138
Foley, Alabama, United States
Research Site 10001-113
Huntsville, Alabama, United States
Research Site 10001-058
Mobile, Alabama, United States
Research Site 10001-037
Montgomery, Alabama, United States
Research Site 10001-076
Saraland, Alabama, United States
Research Site 10001-013
Chandler, Arizona, United States
Research Site 10001-077
Mesa, Arizona, United States
Research Site 10001-136
Phoenix, Arizona, United States
Research Site 10001-051
Surprise, Arizona, United States
Research Site 10001-019
Tucson, Arizona, United States
Research Site 10001-004
Tucson, Arizona, United States
Research Site 10001-132
Tucson, Arizona, United States
Research Site 10001-073
Beverly Hills, California, United States
Research Site 10001-050
Canoga Park, California, United States
Research Site 10001-011
Carlsbad, California, United States
Research Site 10001-065
El Cajon, California, United States
Research Site 10001-150
Los Angeles, California, United States
Research Site 90001-005
Mission Viejo, California, United States
Research Site 10001-043
Northridge, California, United States
Research Site 10001-022
Northridge, California, United States
Research Site 10001-033
Sacramento, California, United States
Research Site 10001-105
San Ramon, California, United States
Research Site 10001-008
Santa Rosa, California, United States
Research Site 10001-153
Spring Valley, California, United States
Research Site 90001-015
Stanford, California, United States
Research Site 10001-044
Torrance, California, United States
Research Site 90001-047
Boca Raton, Florida, United States
Research Site 10001-084
Clearwater, Florida, United States
Research Site 10001-155
Clearwater, Florida, United States
Research Site 10001-099
Clearwater, Florida, United States
Research Site 10001-127
Daytona Beach, Florida, United States
Research Site 10001-119
Fleming Island, Florida, United States
Research Site 10001-070
Fort Lauderdale, Florida, United States
Research Site 10001-067
Hialeah, Florida, United States
Research Site 10001-139
Jacksonville, Florida, United States
Research Site 10001-039
Jacksonville, Florida, United States
Research Site 10001-098
Jacksonville, Florida, United States
Research Site 10001-081
Miami, Florida, United States
Research Site 10001-140
Miami, Florida, United States
Research Site 10001-142
Miami, Florida, United States
Research Site 10001-030
Miami, Florida, United States
Research Site 10001-116
Miami, Florida, United States
Research Site 10001-080
Miami Springs, Florida, United States
Research Site 10001-027
Pembroke Pines, Florida, United States
Research Site 10001-115
Pembroke Pines, Florida, United States
Research Site 10001-048
Pembroke Pines, Florida, United States
Research Site 10001-147
Pembroke Pines, Florida, United States
Research Site 10001-003
Pinellas Park, Florida, United States
Research Site 10001-104
Ponte Vedra, Florida, United States
Research Site 10001-090
Saint Augustine, Florida, United States
Research Site 10001-123
Sarasota, Florida, United States
Research Site 10001-102
St. Petersburg, Florida, United States
Research Site 10001-143
Tampa, Florida, United States
Research Site 10001-069
Atlanta, Georgia, United States
Research Site 10001-137
Dunwoody, Georgia, United States
Research Site 10001-092
Macon, Georgia, United States
Research Site 10001-059
Arlington Heights, Illinois, United States
Research Site 10001-158
Chicago, Illinois, United States
Research Site 10001-036
Evanston, Illinois, United States
Research Site 10001-082
Indianapolis, Indiana, United States
Research Site 10001-040
Valparaiso, Indiana, United States
Research Site 10001-074
West Des Moines, Iowa, United States
Research Site 10001-028
Hutchinson, Kansas, United States
Research Site 10001-125
Lexington, Kentucky, United States
Research Site 10001-108
Lexington, Kentucky, United States
Research Site 10001-107
Owensboro, Kentucky, United States
Research Site 10001-144
Crowley, Louisiana, United States
Research Site 10001-041
Lake Charles, Louisiana, United States
Research Site 10001-101
Monroe, Louisiana, United States
Research Site 90001-004
Boston, Massachusetts, United States
Research Site 10001-024
Flint, Michigan, United States
Research Site 10001-095
Grandville, Michigan, United States
Research Site 10001-078
Sterling Heights, Michigan, United States
Research Site 10001-034
Troy, Michigan, United States
Research Site 10001-018
Edina, Minnesota, United States
Research Site 90001-056
Saint Paul, Minnesota, United States
Research Site 10001-156
St Louis, Missouri, United States
Research Site 10001-007
St Louis, Missouri, United States
Research Site 90001-012
Butte, Montana, United States
Research Site 10001-053
Omaha, Nebraska, United States
Research Site 10001-021
Omaha, Nebraska, United States
Research Site 90001-112
Las Vegas, Nevada, United States
Research Site 10001-124
Las Vegas, Nevada, United States
Research Site 10001-060
Bridgewater, New Jersey, United States
Research Site 90001-014
Summit, New Jersey, United States
Research Site 10001-055
Warren Township, New Jersey, United States
Research Site 10001-054
Albany, New York, United States
Research Site 10001-122
Binghamton, New York, United States
Research Site 10001-128
Endwell, New York, United States
Research Site 10001-042
New Windsor, New York, United States
Research Site 10001-129
Poughkeepsie, New York, United States
Research Site 10001-110
Williamsville, New York, United States
Research Site 10001-063
Cary, North Carolina, United States
Research Site 10001-064
Greensboro, North Carolina, United States
Research Site 10001-145
Mooresville, North Carolina, United States
Research Site 10001-046
Shelby, North Carolina, United States
Research Site 10001-016
Akron, Ohio, United States
Research Site 10001-120
Cincinnati, Ohio, United States
Research Site 90001-002
Cincinnati, Ohio, United States
Research Site 10001-010
Cincinnati, Ohio, United States
Research Site 10001-134
Cincinnati, Ohio, United States
Research Site 10001-014
Columbus, Ohio, United States
Research Site 10001-141
Dayton, Ohio, United States
Research Site 10001-148
Marion, Ohio, United States
Research Site 10001-109
Wyomissing, Pennsylvania, United States
Research Site 10001-001
Anderson, South Carolina, United States
Research Site 10001-006
Greer, South Carolina, United States
Research Site 10001-075.
Greer, South Carolina, United States
Research Site 10001-111
Myrtle Beach, South Carolina, United States
Research Site 10001-133
Pelzer, South Carolina, United States
Research Site 10001-103
Rapid City, South Dakota, United States
Research Site 10001-146
Athens, Tennessee, United States
Research Site 10001-130
Kingsport, Tennessee, United States
Research Site 10001-118
Knoxville, Tennessee, United States
Research Site 10001-106
Knoxville, Tennessee, United States
Research Site 10001-100
Amarillo, Texas, United States
Research Site 10001-087
Austin, Texas, United States
Research Site 10001-117
Austin, Texas, United States
Research Site 10001-009
Dallas, Texas, United States
Research Site 10001-068
Edinburg, Texas, United States
Research Site 10001-031
Houston, Texas, United States
Research Site 10001-088
Houston, Texas, United States
Research Site 10001-091
Houston, Texas, United States
Research Site 10001-061
Houston, Texas, United States
Research Site 10001-032
Houston, Texas, United States
Research Site 10001-057
New Braunfels, Texas, United States
Research Site 10001-079
Round Rock, Texas, United States
Research Site 10001-071
San Antonio, Texas, United States
Research Site 10001-083
Schertz, Texas, United States
Research Site 10001-149
Shavano Park, Texas, United States
Research Site 10001-045
Tomball, Texas, United States
Research Site 10001-005
Layton, Utah, United States
Research Site 10001-002
Salt Lake City, Utah, United States
Research Site 10001-052
Salt Lake City, Utah, United States
Research Site 10001-093
Falls Church, Virginia, United States
Research Site 10001-085
Manassas, Virginia, United States
Research Site 10001-094
Midlothian, Virginia, United States
Research Site 10001-023
Richmond, Virginia, United States
Research Site 10001-029
Suffolk, Virginia, United States
Research Site 10001-114
Tacoma, Washington, United States
Research Site 90011-005
Chicoutimi, Quebec, Canada
Research Site 90011-001
Montreal, Quebec, Canada
Research Site 90011-002
Québec, Quebec, Canada
Research Site 11420-002
Chomutov, , Czechia
Research Site 90420-001
Prague, , Czechia
Research Site 90420-006
Prague, , Czechia
Research Site 11420-003
Uherské Hradiště, , Czechia
Research Site 90045-001
Aalborg, North Denmark, Denmark
Research Site 90045-004
Esbjerg, , Denmark
Research Site 90045-003
Herning, , Denmark
Research Site 90045-006
Hvidovre, , Denmark
Research Site 90045-002
Roskilde, , Denmark
Research Site 90045-005
Viborg, , Denmark
Research Site 11049-006
Berlin, , Germany
Research Site 11049-002
Bochum, , Germany
Research Site 11049-003
Frankfurt, , Germany
Research Site 11049-001
Heidelberg, , Germany
Research Site 11049-007
Heidelberg, , Germany
Research Site 11036-001
Budapest, , Hungary
Research Site 11036-004
Debrecen, , Hungary
Research Site 11036-002
Hatvan, , Hungary
Research Site 11036-003
Zalaegerszeg, , Hungary
Research Site 90031-001
Amersfoort, , Netherlands
Research Site 90031-003
Amsterdam, , Netherlands
Research Site 90031-006
Goes, , Netherlands
Research Site 90031-009
Hoorn, , Netherlands
Research Site 90031-005
Utrecht, , Netherlands
Research SIte 11048-016
Brzozowie, , Poland
Research Site 11048-018
Bydgoszcz, , Poland
Research Site 11048-011
Bydgoszcz, , Poland
Research Site 11048-004
Gdansk, , Poland
Research Site 11048-005
Gdynia, , Poland
Research Site 11048-007
Katowice, , Poland
Research SIte 11048-012
Katowice, , Poland
Research Site 11048-003
Krakow, , Poland
Research SIte 11048-014
Krakow, , Poland
Research Site 11048-008
Lublin, , Poland
Research Site 11048-001
Poznan, , Poland
Research Site 11048-019
Ruda Śląska, , Poland
Research SIte 11048-013
Rzeszów, , Poland
Research SIte 11048-015
Tarnów, , Poland
Research Site 11048-006
Warsaw, , Poland
Research Site 11048-009
Warsaw, , Poland
Research Site 11048-002
Wroclaw, , Poland
Research Site 11048-010
Wroclaw, , Poland
Research Site 90027-008
Bellville, Cape Town, South Africa
Research Site 90027-007
Lyttelton, Cape Town, South Africa
Research Site 90027-003
Bloemfontein, Free State, South Africa
Research Site 90027-010
Johannesburg, Gauteng, South Africa
Research Site 11027-005
Kempton Park, Gauteng, South Africa
Research Site 90027-006
Pretoria, Gauteng, South Africa
Research Site 90027-009
Witbank, Gauteng, South Africa
Research Site 90027-001
Cape Town, Western Cape, South Africa
Research Site 11027-007
Kuils River, Western Cape, South Africa
Research Site 11027-013
Paarl, Western Cape, South Africa
Research Site 90027-004
Somerset West, Western Cape, South Africa
Research Site 90027-005
Somerset West, Western Cape, South Africa
Research Site 90034-004
Córdoba, Andalusia, Spain
Research Site 90034-002
Zaragoza, Aragon, Spain
Research Site 90034-005
Barcelona, Catalonia, Spain
Research Site 90034-006
Barcelona, Catalonia, Spain
Research Site 90034-001
Reus, Catalonia, Spain
Research Site 90034-003
A Coruña, Galicia, Spain
Research Site 90046-002
Gothenburg, , Sweden
Research Site 90046-001
Stockholm, , Sweden
Research Site 90046-003
Stockholm, , Sweden
Research Site 11380-005
Cherkasy, , Ukraine
Research Site 11380-008
Kharkiv, , Ukraine
Research Site 11380-001
Kyiv, , Ukraine
Research Site 11380-002
Kyiv, , Ukraine
Research Site 11380-003
Kyiv, , Ukraine
Research Site 11380-004
Kyiv, , Ukraine
Research Site 11380-006
Uzhhorod, , Ukraine
Research Site 11380-009
Zaporizhzhya, , Ukraine
Research Site 11044-028
Bollington, Cheshire, United Kingdom
Research Site 11044-026
Bury, , United Kingdom
Research Site 11044-024
Cheadle Hulme, , United Kingdom
Research Site 11044-014
Chorley, , United Kingdom
Research Site 11044-012
Cornwell, , United Kingdom
Research Site 11044-010
Derby, , United Kingdom
Research Site 11044-006
Edgbaston, , United Kingdom
Research Site 11044-009
Exeter, , United Kingdom
Research Site 11044-001
Glasgow, , United Kingdom
Research Site 11044-008
Hexham, , United Kingdom
Research SIte 11044-020
Macclesfield, , United Kingdom
Research Site 11044-005
Manchester, , United Kingdom
Research Site 11044-025
Manchester, , United Kingdom
Research Site 11044-027
Manchester, , United Kingdom
Research Site 11044-029
Manchester, , United Kingdom
Research Site 11044-019
Plymouth, , United Kingdom
Research Site 11044-003
Reading, , United Kingdom
Research Site 11044-022
Sale, , United Kingdom
Research Site 11044-023
Sale, , United Kingdom
Research Site 11044-002
Stockton-on-Tees, , United Kingdom
Research Site 11044-021
Timperley, , United Kingdom
Research Site 11044-007
Wales, , United Kingdom
Research Site 11044-004
Waterloo, , United Kingdom
Countries
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References
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Wright RS, Raal FJ, Koenig W, Landmesser U, Leiter LA, Vikarunnessa S, Lesogor A, Maheux P, Talloczy Z, Zang X, Schwartz GG, Ray KK. Inclisiran administration potently and durably lowers LDL-C over an extended-term follow-up: the ORION-8 trial. Cardiovasc Res. 2024 Oct 14;120(12):1400-1410. doi: 10.1093/cvr/cvae109.
Warden BA, Duell PB. Inclisiran: A Novel Agent for Lowering Apolipoprotein B-containing Lipoproteins. J Cardiovasc Pharmacol. 2021 Aug 1;78(2):e157-e174. doi: 10.1097/FJC.0000000000001053.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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CKJX839A12306B
Identifier Type: OTHER
Identifier Source: secondary_id
2017-003092-55
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
MDCO-PCS-17-05
Identifier Type: -
Identifier Source: org_study_id
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