ASCVDPhase 3ORION-10NCT03399370

Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol

A Phase 3 study testing Inclisiran Sodium in people with ASCVD and Elevated Cholesterol, run by The Medicines Company at 145 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This is a Phase III, placebo-controlled, double-blind, randomized study in participants with ASCVD and elevated LDL-C despite maximum tolerated dose of LDL-C lowering therapies to evaluate the efficacy, safety, and tolerability of subcutaneous (SC) inclisiran injection(s). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: ASCVD, Elevated Cholesterol
What is being tested?: Inclisiran Sodium
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,561 participants
Where: 145 sitesUnited States
Study dates: 21 Dec 2017to 17 Sep 2019
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female participants ≥18 years of age.
History of ASCVD (coronary heart disease [CHD], cardiovascular disease [CVD], or peripheral arterial disease [PAD]).
Serum LDL-C ≥1.8 millimole (mmol)/liter (L) (≥70 mg/dL).
Fasting triglyceride <4.52 mmol/L (<400 mg/dL) at screening.
Participants on statins should be receiving a maximally tolerated dose.
Participants not receiving statins must have documented evidence of intolerance to all doses of at least 2 different statins.
Subjects on lipid-lower therapies (such as a statin and/or ezetimibe) should be on a stable dose for ≥30 days before screening with no planned medication or dose change during study participation.

Who cannot join

New York Heart Association (NYHA) class IV heart failure.
Uncontrolled cardiac arrhythmia
Uncontrolled severe hypertension
Active liver disease
Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least 2 methods of highly effective contraception (failure rate less than 1% per year) (for example, combined oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, or intrauterine device) for the entire duration of the study. Exemptions from this criterion:
Women >2 years postmenopausal (defined as 1 year or longer since last menstrual period) and more than 55 years of age.

Show all 12Show fewer

Postmenopausal women (as defined above) and less than 55 years of age with a negative pregnancy test within 24 hours of randomization.
Women who are surgically sterilized at least 3 months prior to enrollment.
Males who are unwilling to use an acceptable method of birth control during the entire study period (such as condom with spermicide).
Treatment with other investigational products or devices within 30 days or 5 half-lives of the screening visit, whichever is longer.
Treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial locations and contacts

145 sites in 1 country.

City, postcode or hospital

145 sites in 1 country

United States145 sites

Research Site 10001-016
Akron, Ohio, 443311
Research Site 10001-054
Albany, New York, 12206
Research Site 10001-100
Amarillo, Texas, 79106
Research Site 10001-001
Anderson, South Carolina, 29621
Research Site 10001-059
Arlington Heights, Illinois, 60005
Research Site 10001-146
Athens, Tennessee, 37303
Research Site 10001-069
Atlanta, Georgia, 30342
Research Site 10001-087
Austin, Texas, 78726
Research Site 10001-117
Austin, Texas, 78756
Research Site 10001-073
Beverly Hills, California, 90211
Research Site 10001-122
Binghamton, New York, 13901
Research Site 10001-015
Birmingham, Alabama, 35211
Research Site 10001-047
Boca Raton, Florida, 33434
Research Site 10001-060
Bridgewater, New Jersey, 08807
Research Site 10001-050
Canoga Park, California, 91303
Research Site 10001-011
Carlsbad, California, 92008
Research Site 10001-063
Cary, North Carolina, 27518
Research Site 10001-013
Chandler, Arizona, 85224
Research Site 10001-158
Chicago, Illinois, 60602
Research Site 10001-035
Chicago, Illinois, 60616
Research Site 10001-120
Cincinnati, Ohio, 45219
Research Site 10001-154
Cincinnati, Ohio, 45227
Research Site 10001-010
Cincinnati, Ohio, 45236
Research Site 10001-134
Cincinnati, Ohio, 45246
Research Site 10001-084
Clearwater, Florida, 33756
Research Site 10001-155
Clearwater, Florida, 33756
Research Site 10001-099
Clearwater, Florida, 33761
Research Site 10001-014
Columbus, Ohio, 43212
Research Site 10001-012
Columbus, Ohio, 43213
Research Site 10001-144
Crowley, Louisiana, 70526
Research Site 10001-009
Dallas, Texas, 75234
Research Site 10001-141
Dayton, Ohio, 45419
Research Site 10001-127
Daytona Beach, Florida, 32117
Research Site 10001-137
Dunwoody, Georgia, 30338
Research Site 10001-018
Edina, Minnesota, 55435
Research Site 10001-068
Edinburg, Texas, 78503
Research Site 10001-017
Edmond, Oklahoma, 73003
Research Site 10001-065
El Cajon, California, 92020
Research Site 10001-128
Endwell, New York, 13760
Research Site 10001-036
Evanston, Illinois, 60201
Research Site 10001-093
Falls Church, Virginia, 22042
Research Site 10001-119
Fleming Island, Florida, 32003
Research Site 10001-024
Flint, Michigan, 48504
Research Site 10001-138
Foley, Alabama, 36535
Research Site 10001-070
Fort Lauderdale, Florida, 33308
Research Site 10001-126
Fort Worth, Texas, 76106
Research Site 10001-095
Grandville, Michigan, 49418
Research Site 10001-064
Greensboro, North Carolina, 27401
Research Site 10001-006
Greer, South Carolina, 29651
Research Site 10001-075.
Greer, South Carolina, 29651
Research Site 10001-067
Hialeah, Florida, 33012
Research Site 10001-031
Houston, Texas, 77002
Research Site 10001-088
Houston, Texas, 77024
Research Site 10001-091
Houston, Texas, 77027
Research Site 10001-061
Houston, Texas, 77058
Research Site 10001-032
Houston, Texas, 77070
Research Site 10001-113
Huntsville, Alabama, 35801
Research Site 10001-028
Hutchinson, Kansas, 67502
Research Site 10001-082
Indianapolis, Indiana, 46260
Research Site 10001-139
Jacksonville, Florida, 32204
Research Site 10001-039
Jacksonville, Florida, 32216
Research Site 10001-098
Jacksonville, Florida, 32216
Research Site 10001-130
Kingsport, Tennessee, 37660
Research Site 10001-118
Knoxville, Tennessee, 37909
Research Site 10001-041
Lake Charles, Louisiana, 70601
Research Site 10001-112
Las Vegas, Nevada, 89119
Research Site 10001-124
Las Vegas, Nevada, 89121
Research Site 10001-005
Layton, Utah, 84041
Research Site 10001-125
Lexington, Kentucky, 40503
Research Site 10001-108
Lexington, Kentucky, 40504
Research Site 10001-150
Los Angeles, California, 90022
Research Site 10001-025
Lubbock, Texas, 79410
Research Site 10001-092
Macon, Georgia, 31210
Research Site 10001-085
Manassas, Virginia, 20110
Research Site 10001-148
Marion, Ohio, 43302
Research Site 10001-077
Mesa, Arizona, 85213
Research Site 10001-081
Miami, Florida, 33126
Research Site 10001-140
Miami, Florida, 33126
Research Site 10001-142
Miami, Florida, 33126
Research Site 10001-030
Miami, Florida, 33165
Research Site 10001-089
Miami, Florida, 33173
Research Site 10001-116
Miami, Florida, 33183
Research Site 10001-080
Miami Springs, Florida, 33166
Research Site 10001-094
Midlothian, Virginia, 23114
Research Site 10001-058
Mobile, Alabama, 36608
Research Site 10001-101
Monroe, Louisiana, 71201
Research Site 10001-037
Montgomery, Alabama, 36117
Research Site 10001-145
Mooresville, North Carolina, 28117
Research Site 10001-111
Myrtle Beach, South Carolina, 29588
Research Site 10001-057
New Braunfels, Texas, 78130
Research Site 10001-042
New Windsor, New York, 12553
Research Site 10001-043
Northridge, California, 91324
Research Site 10001-022
Northridge, California, 91325
Research Site 10001-053
Omaha, Nebraska, 68134
Research Site 10001-021
Omaha, Nebraska, 68144
Research Site 10001-107
Owensboro, Kentucky, 42303
Research Site 10001-133
Pelzer, South Carolina, 29669
Research Site 10001-027
Pembroke Pines, Florida, 33024
Research Site 10001-115
Pembroke Pines, Florida, 33027
Research Site 10001-048
Pembroke Pines, Florida, 33029
Research Site 10001-147
Pembroke Pines, Florida, 33029
Research Site 10001-136
Phoenix, Arizona, 85014
Research Site 10001-003
Pinellas Park, Florida, 33781
Research Site 10001-104
Ponte Vedra, Florida, 32081
Research Site 10001-129
Poughkeepsie, New York, 12601
Research Site 10001-106
Powell, Texas, 37849
Research Site 10001-103
Rapid City, South Dakota, 57701
Research Site 10001-055
Raritan, New Jersey, 08869
Research Site 10001-023
Richmond, Virginia, 23294
Research Site 10001-079
Round Rock, Texas, 78681
Research Site 10001-033
Sacramento, California, 95821-2134
Research Site 10001-090
Saint Augustine, Florida, 32086
Research Site 10001-056
Saint Paul, Minnesota, 55102
Research Site 10001-002
Salt Lake City, Utah, 84123
Research Site 10001-052
Salt Lake City, Utah, 94107
Research Site 10001-071
San Antonio, Texas, 78229
Research Site 10001-105
San Ramon, California, 94582
Research Site 10001-008
Santa Rosa, California, 95405
Research Site 10001-076
Saraland, Alabama, 36571
Research Site 10001-123
Sarasota, Florida, 34239-3513
Research Site 10001-083
Schertz, Texas, 78154
Research Site 1001-020
Sellersburg, Indiana, 47172
Research Site 10001-149
Shavano Park, Texas, 78231
Research Site 10001-046
Shelby, North Carolina, 28150
Research Site 10001-026
Spartanburg, South Carolina, 29303
Research Site 10001-153
Spring Valley, California, 91978
Research Site 10001-156
St Louis, Missouri, 63136
Research Site 10001-007
St Louis, Missouri, 63141
Research Site 10001-102
St. Petersburg, Florida, 33713
Research Site 10001-078
Sterling Heights, Michigan, 48310
Research Site 10001-029
Suffolk, Virginia, 23435
Research Site 10001-051
Surprise, Arizona, 85374
Research Site 10001-114
Tacoma, Washington, 98405
Research Site 10001-038
Tampa, Florida, 33607
Research Site 10001-143
Tampa, Florida, 33614
Research Site 10001-045
Tomball, Texas, 77375
Research Site 10001-044
Torrance, California, 90502
Research Site 10001-034
Troy, Michigan, 48098
Research Site 10001-019
Tucson, Arizona, 85712
Research Site 10001-004
Tucson, Arizona, 85741
Research Site 10001-132
Tucson, Arizona, 85745
Research Site 10001-040
Valparaiso, Indiana, 46383
Research Site 10001-074
West Des Moines, Iowa, 50266
Research Site 10001-110
Williamsville, New York, 14221
Research Site 10001-109
Wyomissing, Pennsylvania, 19610

Other trials in United States

About this study

Official title: A Placebo-Controlled, Double-Blind, Randomized Trial to Evaluate the Effect of 300 mg of Inclisiran Sodium Given as Subcutaneous Injections in Subjects With Atherosclerotic Cardiovascular Disease (ASCVD) and Elevated Low-Density Lipoprotein Cholesterol (LDL-C)

Conditions: ASCVD, Elevated Cholesterol
Being tested: Inclisiran Sodium, Placebo
Keywords: Inclisiran sodium, ASCVD, LDL-C
Medical subject headings: Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Inclisiran SodiumDrug
Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
PlaceboDrug
Also called Saline Solution
Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).

Study groups in NCT03399370
Study group	Role	What they receive
Inclisiran	Experimental	Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90, then every 6 months. Receives: Drug: Inclisiran Sodium
Saline Solution	Placebo comparator	Placebo will be administered as a SC injection of saline solution on Day 1, Day 90, then every 6 months. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage Change in LDL-C From Baseline to Day 510
Measured: Baseline, Day 510
Time-adjusted Percentage Change in LDL-C Levels From Baseline After Day 90 and up to Day 540
Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 540 reported
Measured: Baseline, Day 90 to Day 540

Secondary outcomes (6)

Absolute Change in LDL-C From Baseline to Day 510
Measured: Baseline, Day 510
Time-adjusted Absolute Change in LDL-C From Baseline After Day 90 and up to Day 540
Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 540 reported
Measured: Baseline, Day 90 to Day 540
Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510
Measured: Baseline, Day 510
Percentage Change in Total Cholesterol From Baseline to Day 510
Measured: Baseline, Day 510
Percentage Change in Apolipoprotein B (ApoB) From Baseline to Day 510
Measured: Baseline, Day 510
Percentage Change in Non-HDL-C From Baseline to Day 510
Measured: Baseline, Day 510

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Dec 201717 Sep 2019

First posted16 Jan 2018
Study start21 Dec 2017
Primary completion10 Sep 2019
Study completion17 Sep 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for ASCVDStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Care provider
Enrolment: 1,561 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03399370
Sponsor's protocol ID: MDCO-PCS-17-04
Acronym: ORION-10
Status last verified: Sep 2020
First submitted: 3 Jan 2018
Last updated: 5 Oct 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Landmesser U, Ray KK, Raal FJ, Garcia Conde L, Han J, Koenig W, Leiter LA, Schwartz GG, Wright RS; on behalf of the ORION Investigators. Inclisiran in Patients with CKD: Post Hoc Pooled Analysis of Three Phase 3 Trials. J Am Soc Nephrol. 2026 Jul 1;37(7):1497-1506. doi: 10.1681/ASN.0000001006. Epub 2026 Jan 28.
PubMed 41604274
Leiter LA, Raal FJ, Schwartz GG, Koenig W, Ray KK, Landmesser U, Han J, Conde LG, Wright RS. Inclisiran in individuals with diabetes or obesity: Post hoc pooled analyses of the ORION-9, ORION-10 and ORION-11 Phase 3 randomized trials. Diabetes Obes Metab. 2024 Aug;26(8):3223-3237. doi: 10.1111/dom.15650. Epub 2024 May 17.
PubMed 38757725
Dutta S, Shah R, Singhal S, Singh S, Piparva K, Katoch CDS. A systematic review and meta-analysis of tolerability, cardiac safety and efficacy of inclisiran for the therapy of hyperlipidemic patients. Expert Opin Drug Saf. 2024 Feb;23(2):187-198. doi: 10.1080/14740338.2023.2293201. Epub 2023 Dec 19.
PubMed 38063346
Ray KK, Wright RS. Plain language summary of results from ORION-10 and ORION-11: two studies to learn how well inclisiran works in people with high cholesterol. Future Cardiol. 2023 Mar;19(4):175-184. doi: 10.2217/fca-2022-0133. Epub 2023 Jun 6.
PubMed 37282500
Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, Bisch JA, Richardson T, Jaros M, Wijngaard PLJ, Kastelein JJP; ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020 Apr 16;382(16):1507-1519. doi: 10.1056/NEJMoa1912387. Epub 2020 Mar 18.
PubMed 32187462

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Not yet recruiting
Hs-CRP-Guided Colchicine Treatment Targets in Very-High-Risk Patients With Coronary Artery Disease After PCI (TARGET-CHD)
Coronary Artery Disease, Atherosclerotic Cardiovascular Disease (ASCVD)
RecruitingPhase 2
A Study of Clazakizumab (LY5724886) in Adults With Elevated hsCRP and at Increased Risk for Cardiovascular Event
Atherosclerosis, Cardiovascular Disease
RecruitingObservational study
Late Subclinical Cardiovascular Disease in Testicular Cancer Survivors
Testicular Cancer, Survivorship
Active, not recruitingPhase 2
Phase 2 Study of Kylo-11 in ASCVD Patients With Elevated Lp(a)
Lipoprotein Disorder

All ASCVD trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Placebo-Controlled, Double-Blind, Randomized Trial to Evaluate the Effect of 300 mg of Inclisiran Sodium Given as Subcutaneous Injections in Subjects With Atherosclerotic Cardiovascular Disease (ASCVD) and Elevated Low-Density Lipoprotein Cholesterol (LDL-C)
ClinicalTrials.gov ID: NCT03399370
Acronym / sponsor ID: ORION-10 / MDCO-PCS-17-04
Conditions: ASCVD, Elevated Cholesterol
Keywords: Inclisiran sodium, ASCVD, LDL-C
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,561 participants (actual)
Lead sponsor: The Medicines CompanyIndustry (pharma, biotech, devices)
Study start: 21 Dec 2017 (actual)
Primary completion: 10 Sep 2019 (actual)
Study completion: 17 Sep 2019 (actual)
First posted: 16 Jan 2018 (actual)
Results: Posted 5 Oct 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, care provider)
Number of arms: 2

Arm	Type	Receives
Inclisiran	Experimental	Drug: Inclisiran SodiumInclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90, then every 6 months.
Saline Solution	Placebo comparator	Drug: PlaceboPlacebo will be administered as a SC injection of saline solution on Day 1, Day 90, then every 6 months.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Male or female participants ≥18 years of age.
History of ASCVD (coronary heart disease [CHD], cardiovascular disease [CVD], or peripheral arterial disease [PAD]).
Serum LDL-C ≥1.8 millimole (mmol)/liter (L) (≥70 mg/dL).
Fasting triglyceride <4.52 mmol/L (<400 mg/dL) at screening.
Participants on statins should be receiving a maximally tolerated dose.

Key exclusion criteria (12 listed)

New York Heart Association (NYHA) class IV heart failure.
Uncontrolled cardiac arrhythmia
Uncontrolled severe hypertension
Active liver disease
Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least 2 methods of highly effective contraception (failure rate less than 1% per year) (for example, combined oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, or intrauterine device) for the entire duration of the study. Exemptions from this criterion:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Inclisiran SodiumInclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.	Drug	Inclisiran
PlaceboAlso: Saline SolutionPlacebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).	Drug	Saline Solution

Primary outcome

Percentage Change in LDL-C From Baseline to Day 510
Time frame: Baseline, Day 510
Time-adjusted Percentage Change in LDL-C Levels From Baseline After Day 90 and up to Day 540
Time frame: Baseline, Day 90 to Day 540
Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 540 reported

6 secondary outcomes

Absolute Change in LDL-C From Baseline to Day 510
Time frame: Baseline, Day 510
Time-adjusted Absolute Change in LDL-C From Baseline After Day 90 and up to Day 540
Time frame: Baseline, Day 90 to Day 540
Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510
Time frame: Baseline, Day 510
Percentage Change in Total Cholesterol From Baseline to Day 510
Time frame: Baseline, Day 510
Percentage Change in Apolipoprotein B (ApoB) From Baseline to Day 510
Time frame: Baseline, Day 510
Percentage Change in Non-HDL-C From Baseline to Day 510
Time frame: Baseline, Day 510

Results and safety

Results posted to the registry on 5 Oct 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Inclisiran	781	721
Saline Solution	780	694

Primary outcome: Percentage Change in LDL-C From Baseline to Day 510

Time frame: Baseline, Day 510. Least squares mean (95% Confidence Interval). Unit: percent change

Measure	Inclisiran n = 781	Placebo n = 780
Value	-56.34 (-58.35 to -54.34)	1.30 (-1.24 to 3.83)

Inclisiran vs Placebo: Mean Difference (Final Values): -57.64 (95% CI -60.86 to -54.43), p <.0001, ANCOVA

Population analysed: Intent-to-treat (ITT) population

Primary outcome: Time-adjusted Percentage Change in LDL-C Levels From Baseline After Day 90 and up to Day 540

Time frame: Baseline, Day 90 to Day 540. Least squares mean (95% Confidence Interval). Unit: percent change

Measure	Inclisiran n = 781	Placebo n = 790
Value	-51.27 (-53.00 to -49.54)	2.51 (0.77 to 4.25)

Inclisiran vs Placebo: Mean Difference (Final Values): -53.78 (95% CI -56.23 to -51.33), p <0.0001, ANCOVA

Population analysed: Intent-to-treat (ITT) population

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: 18 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Inclisiran	175 of 781 (22.4%)	247 of 781 (31.6%)	12 of 781
Saline Solution	205 of 778 (26.3%)	219 of 778 (28.1%)	11 of 778

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 41604274Landmesser U, Ray KK, Raal FJ, Garcia Conde L, Han J, Koenig W, Leiter LA, Schwartz GG, Wright RS; on behalf of the ORION Investigators. Inclisiran in Patients with CKD: Post Hoc Pooled Analysis of Three Phase 3 Trials. J Am Soc Nephrol. 2026 Jul 1;37(7):1497-1506. doi: 10.1681/ASN.0000001006. Epub 2026 Jan 28.
Derived from this study: PubMed 38757725Leiter LA, Raal FJ, Schwartz GG, Koenig W, Ray KK, Landmesser U, Han J, Conde LG, Wright RS. Inclisiran in individuals with diabetes or obesity: Post hoc pooled analyses of the ORION-9, ORION-10 and ORION-11 Phase 3 randomized trials. Diabetes Obes Metab. 2024 Aug;26(8):3223-3237. doi: 10.1111/dom.15650. Epub 2024 May 17.
Derived from this study: PubMed 38063346Dutta S, Shah R, Singhal S, Singh S, Piparva K, Katoch CDS. A systematic review and meta-analysis of tolerability, cardiac safety and efficacy of inclisiran for the therapy of hyperlipidemic patients. Expert Opin Drug Saf. 2024 Feb;23(2):187-198. doi: 10.1080/14740338.2023.2293201. Epub 2023 Dec 19.
Derived from this study: PubMed 37282500Ray KK, Wright RS. Plain language summary of results from ORION-10 and ORION-11: two studies to learn how well inclisiran works in people with high cholesterol. Future Cardiol. 2023 Mar;19(4):175-184. doi: 10.2217/fca-2022-0133. Epub 2023 Jun 6.
Derived from this study: PubMed 32187462Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, Bisch JA, Richardson T, Jaros M, Wijngaard PLJ, Kastelein JJP; ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020 Apr 16;382(16):1507-1519. doi: 10.1056/NEJMoa1912387. Epub 2020 Mar 18.

Related trials for ASCVD

Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Not yet recruiting
Hs-CRP-Guided Colchicine Treatment Targets in Very-High-Risk Patients With Coronary Artery Disease After PCI (TARGET-CHD)
Coronary Artery Disease, Atherosclerotic Cardiovascular Disease (ASCVD)
RecruitingPhase 2
A Study of Clazakizumab (LY5724886) in Adults With Elevated hsCRP and at Increased Risk for Cardiovascular Event
Atherosclerosis, Cardiovascular Disease
RecruitingObservational study
Late Subclinical Cardiovascular Disease in Testicular Cancer Survivors
Testicular Cancer, Survivorship
Active, not recruitingPhase 2
Phase 2 Study of Kylo-11 in ASCVD Patients With Elevated Lp(a)
Lipoprotein Disorder

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Scott Wright, MD principal investigator

Mayo Clinic

145 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Inclisiran Sodium in people with ASCVD and Elevated Cholesterol, run by The Medicines Company at 145 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 145 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage Change in LDL-C From Baseline to Day 510 (time frame: Baseline, Day 510). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03399370, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2020.