Trial to Assess the Effect of Long Term Dosing of Inclisiran in Subjects With High CV Risk and Elevated LDL-C (ORION-8)

An Open-label Extension Trial of the Phase III Lipid-lowering Trials to Assess the Effect of Long Term Dosing of Inclisiran Given as Subcutaneous Injections in Subjects With High Cardiovascular Risk and Elevated LDL-C

The purpose of this extension study was to evaluate the efficacy, safety, and tolerability of long-term dosing of Inclisiran. The study was a global multicenter study.

Study Overview

• Status: Completed
• Conditions: Elevated Cholesterol; Homozygous Familial Hypercholesterolemia; Heterozygous Familial Hypercholesterolemia; ASCVD
• Intervention / Treatment: Drug: Inclisiran Sodium

Detailed Description

This study was an open label, long term extension study in subjects with atherosclerotic cardiovascular disease (ASCVD), ASCVD-risk equivalents (eg, diabetes and familial hypercholesterolemia), or heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C) despite maximum tolerated dose of LDL-C lowering therapies who have completed the inclisiran Phase II trial MDCO-PCS-16-01 (ORION-3; NCT03060577), or any of the following Phase III lipid lowering studies: MDCO-PCS-17-03 (ORION-9; NCT03397121), MDCO-PCS-17-04 (ORION-10; NCT03399370), or MDCO-PCS-17-08 (ORION-11; NCT03400800).

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.

• Study Type: Interventional
• Enrollment (Actual): 3275
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Research Site 90011-005
    • Montréal, Quebec, Canada, H2W 1R7
      • Research Site 90011-001
    • Québec, Quebec, Canada, GIV 4W2
      • Research Site 90011-002
• Czechia
  • Chomutov, Czechia, 430 02
    • Research Site 11420-002
  • Praha, Czechia, 140 21
    • Research Site 90420-001
  • Praha, Czechia, 180 81
    • Research Site 90420-006
  • Uherské Hradiště, Czechia, 686 01
    • Research Site 11420-003
• Denmark
  • Esbjerg, Denmark, 6700
    • Research Site 90045-004
  • Herning, Denmark, 7400
    • Research Site 90045-003
  • Hvidovre, Denmark, 2650
    • Research Site 90045-006
  • Roskilde, Denmark, 4000
    • Research Site 90045-002
  • Viborg, Denmark, 8800
    • Research Site 90045-005
  • Nordjylland
    • Aalborg, Nordjylland, Denmark, 9000
      • Research Site 90045-001
• Germany
  • Berlin, Germany, 12627
    • Research Site 11049-006
  • Bochum, Germany, 47787
    • Research Site 11049-002
  • Frankfurt, Germany, 60313
    • Research Site 11049-003
  • Heidelberg, Germany, 69120
    • Research Site 11049-001
  • Heidelberg, Germany, 69120
    • Research Site 11049-007
• Hungary
  • Budapest, Hungary
    • Research Site 11036-001
  • Debrecen, Hungary
    • Research Site 11036-004
  • Hatvan, Hungary
    • Research Site 11036-002
  • Zalaegerszeg, Hungary
    • Research Site 11036-003
• Netherlands
  • Amersfoort, Netherlands, 3813 TZ
    • Research Site 90031-001
  • Amsterdam, Netherlands, 1105 AZ
    • Research Site 90031-003
  • Goes, Netherlands, 4462 RA
    • Research Site 90031-006
  • Hoorn, Netherlands, 1624 NP
    • Research Site 90031-009
  • Utrecht, Netherlands
    • Research Site 90031-005
• Poland
  • Brzozowie, Poland
    • Research SIte 11048-016
  • Bydgoszcz, Poland, 85-079
    • Research Site 11048-018
  • Bydgoszcz, Poland
    • Research Site 11048-011
  • Gdańsk, Poland
    • Research Site 11048-004
  • Gdynia, Poland
    • Research Site 11048-005
  • Katowice, Poland
    • Research Site 11048-007
  • Katowice, Poland
    • Research SIte 11048-012
  • Kraków, Poland
    • Research Site 11048-003
  • Kraków, Poland
    • Research SIte 11048-014
  • Lublin, Poland
    • Research Site 11048-008
  • Poznań, Poland
    • Research Site 11048-001
  • Ruda Śląska, Poland, 41-709
    • Research Site 11048-019
  • Rzeszów, Poland
    • Research SIte 11048-013
  • Tarnów, Poland
    • Research SIte 11048-015
  • Warsaw, Poland
    • Research Site 11048-006
  • Warsaw, Poland
    • Research Site 11048-009
  • Wrocław, Poland
    • Research Site 11048-002
  • Wrocław, Poland
    • Research Site 11048-010
• South Africa
  • Cape Town
    • Bellville, Cape Town, South Africa, 7530
      • Research Site 90027-008
    • Lyttelton, Cape Town, South Africa, 0157
      • Research Site 90027-007
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Research Site 90027-003
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Research Site 90027-010
    • Kempton Park, Gauteng, South Africa, 1619
      • Research Site 11027-005
    • Pretoria, Gauteng, South Africa, 0184
      • Research Site 90027-006
    • Witbank, Gauteng, South Africa, 1035
      • Research Site 90027-009
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7500
      • Research Site 90027-001
    • Kuilsrivier, Western Cape, South Africa, 7580
      • Research Site 11027-007
    • Paarl, Western Cape, South Africa, 7646
      • Research Site 11027-013
    • Somerset West, Western Cape, South Africa, 7130
      • Research Site 90027-004
    • Somerset West, Western Cape, South Africa, 7130
      • Research Site 90027-005
• Spain
  • Andalucia
    • Córdoba, Andalucia, Spain, 14004
      • Research Site 90034-004
  • Aragon
    • Zaragoza, Aragon, Spain, 5009
      • Research Site 90034-002
  • Cataluna
    • Barcelona, Cataluna, Spain, 08036
      • Research Site 90034-005
    • Barcelona, Cataluna, Spain, 08907
      • Research Site 90034-006
    • Reus, Cataluna, Spain, 43204
      • Research Site 90034-001
  • Galicia
    • La Coruña, Galicia, Spain, 15002
      • Research Site 90034-003
• Sweden
  • Göteborg, Sweden, SE-41346
    • Research Site 90046-002
  • Stockholm, Sweden, SE-11446
    • Research Site 90046-001
  • Stockholm, Sweden, SE-14186
    • Research Site 90046-003
• Ukraine
  • Cherkasy, Ukraine
    • Research Site 11380-005
  • Kharkiv, Ukraine, 61176
    • Research Site 11380-008
  • Kyiv, Ukraine, 02002
    • Research Site 11380-001
  • Kyiv, Ukraine, 03037
    • Research Site 11380-002
  • Kyiv, Ukraine, 03049
    • Research Site 11380-003
  • Kyiv, Ukraine
    • Research Site 11380-004
  • Zaporizhzhya, Ukraine
    • Research Site 11380-009
  • Úzhgorod, Ukraine, 88000
    • Research Site 11380-006
• United Kingdom
  • Bury, United Kingdom
    • Research Site 11044-026
  • Cheadle Hulme, United Kingdom
    • Research Site 11044-024
  • Chorley, United Kingdom
    • Research Site 11044-014
  • Cornwell, United Kingdom
    • Research Site 11044-012
  • Derby, United Kingdom
    • Research Site 11044-010
  • Edgbaston, United Kingdom
    • Research Site 11044-006
  • Exeter, United Kingdom
    • Research Site 11044-009
  • Glasgow, United Kingdom
    • Research Site 11044-001
  • Hexham, United Kingdom
    • Research Site 11044-008
  • Macclesfield, United Kingdom
    • Research SIte 11044-020
  • Manchester, 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
  • Plymouth, United Kingdom
    • Research Site 11044-019
  • Reading, United Kingdom
    • Research Site 11044-003
  • Sale, United Kingdom
    • Research Site 11044-022
  • Sale, United Kingdom
    • Research Site 11044-023
  • Stockton-on-Tees, United Kingdom
    • Research Site 11044-002
  • Timperley, United Kingdom
    • Research Site 11044-021
  • Wales, United Kingdom
    • Research Site 11044-007
  • Waterloo, United Kingdom
    • Research Site 11044-004
  • Cheshire
    • Bollington, Cheshire, United Kingdom, SK10 5JH
      • Research Site 11044-028
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Research Site 10001-015
    • Foley, Alabama, United States, 36535
      • Research Site 10001-138
    • Huntsville, Alabama, United States, 35801
      • Research Site 10001-113
    • Mobile, Alabama, United States, 36608
      • Research Site 10001-058
    • Montgomery, Alabama, United States, 36117
      • Research Site 10001-037
    • Saraland, Alabama, United States, 36571
      • Research Site 10001-076
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Research Site 10001-013
    • Mesa, Arizona, United States, 85213
      • Research Site 10001-077
    • Phoenix, Arizona, United States, 85014
      • Research Site 10001-136
    • Surprise, Arizona, United States, 85374
      • Research Site 10001-051
    • Tucson, Arizona, United States, 85712
      • Research Site 10001-019
    • Tucson, Arizona, United States, 85741
      • Research Site 10001-004
    • Tucson, Arizona, United States, 85745
      • Research Site 10001-132
  • California
    • Beverly Hills, California, United States, 90211
      • Research Site 10001-073
    • Canoga Park, California, United States, 91303
      • Research Site 10001-050
    • Carlsbad, California, United States, 92008
      • Research Site 10001-011
    • El Cajon, California, United States, 92020
      • Research Site 10001-065
    • Los Angeles, California, United States, 90022
      • Research Site 10001-150
    • Mission Viejo, California, United States, 92691
      • Research Site 90001-005
    • Northridge, California, United States, 91324
      • Research Site 10001-043
    • Northridge, California, United States, 91325
      • Research Site 10001-022
    • Sacramento, California, United States, 95821-2134
      • Research Site 10001-033
    • San Ramon, California, United States, 94582
      • Research Site 10001-105
    • Santa Rosa, California, United States, 95405
      • Research Site 10001-008
    • Spring Valley, California, United States, 91978
      • Research Site 10001-153
    • Stanford, California, United States, 94305
      • Research Site 90001-015
    • Torrance, California, United States, 90502
      • Research Site 10001-044
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Research Site 90001-047
    • Clearwater, Florida, United States, 33756
      • Research Site 10001-084
    • Clearwater, Florida, United States, 33756
      • Research Site 10001-155
    • Clearwater, Florida, United States, 33761
      • Research Site 10001-099
    • Daytona Beach, Florida, United States, 32117
      • Research Site 10001-127
    • Fleming Island, Florida, United States, 32003
      • Research Site 10001-119
    • Fort Lauderdale, Florida, United States, 33308
      • Research Site 10001-070
    • Hialeah, Florida, United States, 33012
      • Research Site 10001-067
    • Jacksonville, Florida, United States, 32204
      • Research Site 10001-139
    • Jacksonville, Florida, United States, 32216
      • Research Site 10001-039
    • Jacksonville, Florida, United States, 32216
      • Research Site 10001-098
    • Miami, Florida, United States, 33126
      • Research Site 10001-081
    • Miami, Florida, United States, 33126
      • Research Site 10001-140
    • Miami, Florida, United States, 33126
      • Research Site 10001-142
    • Miami, Florida, United States, 33165
      • Research Site 10001-030
    • Miami, Florida, United States, 33183
      • Research Site 10001-116
    • Miami Springs, Florida, United States, 33166
      • Research Site 10001-080
    • Pembroke Pines, Florida, United States, 33024
      • Research Site 10001-027
    • Pembroke Pines, Florida, United States, 33027
      • Research Site 10001-115
    • Pembroke Pines, Florida, United States, 33029
      • Research Site 10001-048
    • Pembroke Pines, Florida, United States, 33029
      • Research Site 10001-147
    • Pinellas Park, Florida, United States, 33781
      • Research Site 10001-003
    • Ponte Vedra, Florida, United States, 32081
      • Research Site 10001-104
    • Saint Augustine, Florida, United States, 32086
      • Research Site 10001-090
    • Saint Petersburg, Florida, United States, 33713
      • Research Site 10001-102
    • Sarasota, Florida, United States, 34239-3513
      • Research Site 10001-123
    • Tampa, Florida, United States, 33614
      • Research Site 10001-143
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Research Site 10001-069
    • Dunwoody, Georgia, United States, 30338
      • Research Site 10001-137
    • Macon, Georgia, United States, 31210
      • Research Site 10001-092
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Research Site 10001-059
    • Chicago, Illinois, United States, 60652
      • Research Site 10001-158
    • Evanston, Illinois, United States, 60201
      • Research Site 10001-036
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Research Site 10001-082
    • Valparaiso, Indiana, United States, 46383
      • Research Site 10001-040
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Research Site 10001-074
  • Kansas
    • Hutchinson, Kansas, United States, 67502
      • Research Site 10001-028
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Research Site 10001-125
    • Lexington, Kentucky, United States, 40504
      • Research Site 10001-108
    • Owensboro, Kentucky, United States, 42303
      • Research Site 10001-107
  • Louisiana
    • Crowley, Louisiana, United States, 70526
      • Research Site 10001-144
    • Lake Charles, Louisiana, United States, 70601
      • Research Site 10001-041
    • Monroe, Louisiana, United States, 71201
      • Research Site 10001-101
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Research Site 90001-004
  • Michigan
    • Flint, Michigan, United States, 48504
      • Research Site 10001-024
    • Grandville, Michigan, United States, 49418
      • Research Site 10001-095
    • Sterling Heights, Michigan, United States, 48310
      • Research Site 10001-078
    • Troy, Michigan, United States, 48098
      • Research Site 10001-034
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Research Site 10001-018
    • Saint Paul, Minnesota, United States, 55102
      • Research Site 90001-056
  • Missouri
    • Saint Louis, Missouri, United States, 63136
      • Research Site 10001-156
    • Saint Louis, Missouri, United States, 63141
      • Research Site 10001-007
  • Montana
    • Butte, Montana, United States, 59701
      • Research Site 90001-012
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Research Site 10001-053
    • Omaha, Nebraska, United States, 68144
      • Research Site 10001-021
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Research Site 90001-112
    • Las Vegas, Nevada, United States, 89121
      • Research Site 10001-124
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Research Site 10001-060
    • Summit, New Jersey, United States, 07901
      • Research Site 90001-014
    • Warren, New Jersey, United States, 07059
      • Research Site 10001-055
  • New York
    • Albany, New York, United States, 12206
      • Research Site 10001-054
    • Binghamton, New York, United States, 13901
      • Research Site 10001-122
    • Endwell, New York, United States, 13760
      • Research Site 10001-128
    • New Windsor, New York, United States, 12553
      • Research Site 10001-042
    • Poughkeepsie, New York, United States, 12601
      • Research Site 10001-129
    • Williamsville, New York, United States, 14221
      • Research Site 10001-110
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Research Site 10001-063
    • Greensboro, North Carolina, United States, 27401
      • Research Site 10001-064
    • Mooresville, North Carolina, United States, 28117
      • Research Site 10001-145
    • Shelby, North Carolina, United States, 28150
      • Research Site 10001-046
  • Ohio
    • Akron, Ohio, United States, 443311
      • Research Site 10001-016
    • Cincinnati, Ohio, United States, 45219
      • Research Site 10001-120
    • Cincinnati, Ohio, United States, 45227
      • Research Site 90001-002
    • Cincinnati, Ohio, United States, 45236
      • Research Site 10001-010
    • Cincinnati, Ohio, United States, 45246
      • Research Site 10001-134
    • Columbus, Ohio, United States, 43212
      • Research Site 10001-014
    • Dayton, Ohio, United States, 45419
      • Research Site 10001-141
    • Marion, Ohio, United States, 43302
      • Research Site 10001-148
  • Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Research Site 10001-109
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Research Site 10001-001
    • Greer, South Carolina, United States, 29651
      • Research Site 10001-006
    • Greer, South Carolina, United States, 29651
      • Research Site 10001-075.
    • Myrtle Beach, South Carolina, United States, 29588
      • Research Site 10001-111
    • Pelzer, South Carolina, United States, 29669
      • Research Site 10001-133
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Research Site 10001-103
  • Tennessee
    • Athens, Tennessee, United States, 37303
      • Research Site 10001-146
    • Kingsport, Tennessee, United States, 37660
      • Research Site 10001-130
    • Knoxville, Tennessee, United States, 37909
      • Research Site 10001-118
    • Knoxville, Tennessee, United States, 37917
      • Research Site 10001-106
  • Texas
    • Amarillo, Texas, United States, 79106
      • Research Site 10001-100
    • Austin, Texas, United States, 78726
      • Research Site 10001-087
    • Austin, Texas, United States, 78756
      • Research Site 10001-117
    • Dallas, Texas, United States, 75234
      • Research Site 10001-009
    • Edinburg, Texas, United States, 78503
      • Research Site 10001-068
    • Houston, Texas, United States, 77002
      • Research Site 10001-031
    • Houston, Texas, United States, 77024
      • Research Site 10001-088
    • Houston, Texas, United States, 77027
      • Research Site 10001-091
    • Houston, Texas, United States, 77058
      • Research Site 10001-061
    • Houston, Texas, United States, 77070
      • Research Site 10001-032
    • New Braunfels, Texas, United States, 78130
      • Research Site 10001-057
    • Round Rock, Texas, United States, 78681
      • Research Site 10001-079
    • San Antonio, Texas, United States, 78229
      • Research Site 10001-071
    • Schertz, Texas, United States, 78154
      • Research Site 10001-083
    • Shavano Park, Texas, United States, 78231
      • Research Site 10001-149
    • Tomball, Texas, United States, 77375
      • Research Site 10001-045
  • Utah
    • Layton, Utah, United States, 84041
      • Research Site 10001-005
    • Salt Lake City, Utah, United States, 84123
      • Research Site 10001-002
    • Salt Lake City, Utah, United States, 94107
      • Research Site 10001-052
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Research Site 10001-093
    • Manassas, Virginia, United States, 20110
      • Research Site 10001-085
    • Midlothian, Virginia, United States, 23114
      • Research Site 10001-094
    • Richmond, Virginia, United States, 23294
      • Research Site 10001-023
    • Suffolk, Virginia, United States, 23435
      • Research Site 10001-029
  • Washington
    • Tacoma, Washington, United States, 98405
      • Research Site 10001-114

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Completion on a previously qualifying inclisiran Phase II trial MDCO-PCS-16-01 (ORION-3), or Phase III lipid lowering ORION feeder study [MDCO-PCS-17-03 (ORION-9), MDCO-PCS-17-4 (ORION-10), or MDCO-PCS-17-08 (ORION-11)] meaning the subject received the last dose of study drug and completed the final study visit per applicable protocol.
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:

1. Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study, and/or put the subject at significant risk [according to investigator's (or delegate's) judgment] if he/she participates in the clinical study.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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

Drug: Inclisiran Sodium; Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Achieving Global Lipid Targets for Their Level of ASCVD Risk	The primary objective of the study is to evaluate the effect of inclisiran treatment on the proportion of subjects achieving prespecified LDL-C targets at end of study (EOS). Target is <70 mg/dL for atherosclerotic cardiovascular disease (ASCVD) subjects and <100 mg/dL for ASCVD risk equivalent subjects. Risk equivalent subjects are defined as either type 2 diabetes, familial hypercholesterolemia or a 10-year risk of a cardiovascular event ≥20% as assessed by the Framingham Risk Score or equivalent; without a medical history of coronary heart disease , cerebrovascular disease or peripheral artery disease.	From ORION-8 Day 1 to the end of study (up to 1080 days)
Incidence of Treatment-emergent Adverse Events (TEAEs)	Safety assessments include adverse events and serious adverse events until the end of study. End of study visit occured at least 90 days following the last inclisiran dose once a decision was made to end the study (either by the subject, investigator or sponsor). For subjects prematurely and permanently discontinued from study treatment, who were not willing to return within the 90 day timeframe, the EOS visit was scheduled as soon as possible, or if decision to discontinue and not return was made at a specific visit, this visit became the EOS visit.	From ORION-8 Day 1 to the end of study (up to 1080 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in LDL-C From the Initial Feeder Study Baseline	Absolute change from baseline in low density lipoprotein cholesterol (LDL-C) was calculated to evaluate the effect of inclisiran on LDL-C levels.	Feeder study baseline, ORION-8 baseline, Day 1080/EOS (ORION-8) (up to a maximum of 2340 days)
Percentage Change in LDL-C From the Initial Feeder Study Baseline	Percentage change from baseline in low density lipoprotein cholesterol (LDL-C) was calculated to evaluate the effect of inclisiran on LDL-C levels.	Feeder study baseline, ORION-8 baseline, Day 1080/EOS (ORION-8) (up to a maximum of 2340 days)
Absolute Change From the Initial Feeder Study Baseline in Total Cholesterol, Triglycerides and HDL-C	Absolute change from baseline in total cholesterol, triglycerides and high density lipoprotein cholesterol (HDL-C) was calculated to evaluate the effect of inclisiran on other lipids and lipoproteins.	Feeder study baseline, ORION-8 baseline, Day 1080/EOS (ORION-8) (up to a maximum of 2340 days)
Percentage Change From the Initial Feeder Study Baseline in Total Cholesterol, Triglycerides and HDL-C	Percentage change from baseline in total cholesterol (TC), triglycerides and high density lipoprotein cholesterol (HDL-C) was calculated to evaluate the effect of inclisiran on other lipids and lipoproteins.	Feeder study baseline, ORION-8 baseline, Day 1080/EOS (ORION-8) (up to a maximum of 2340 days)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Scott Wright, MD, Mayo Clinic

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2019
• Primary Completion (Actual): February 13, 2023
• Study Completion (Actual): February 13, 2023

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: January 22, 2019
• First Posted (Actual): January 23, 2019

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: LDL-C; ASCVD; HeFH; HoFH; Inclisiran sodium
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II; Homozygous Familial Hypercholesterolemia
• Other Study ID Numbers: MDCO-PCS-17-05; CKJX839A12306B (Other Identifier: Novartis Pharmaceuticals); 2017-003092-55 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No