Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol (ORION-10)

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)

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). The study will be a multicenter study in the United States.

Study Overview

• Status: Completed
• Conditions: Elevated Cholesterol; ASCVD
• Intervention / Treatment: Drug: Inclisiran Sodium; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1561
• Phase: Phase 3

Contacts and Locations

Study Locations

• 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
    • 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
    • Torrance, California, United States, 90502
      • Research Site 10001-044
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Research Site 10001-047
    • 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, Florida, United States, 33173
      • Research Site 10001-089
    • 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
    • Tampa, Florida, United States, 33607
      • Research Site 10001-038
  • 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, 60602
      • Research Site 10001-158
    • Chicago, Illinois, United States, 60616
      • Research Site 10001-035
    • Evanston, Illinois, United States, 60201
      • Research Site 10001-036
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Research Site 10001-082
    • Sellersburg, Indiana, United States, 47172
      • Research Site 1001-020
    • 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
  • 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 10001-056
  • Missouri
    • Saint Louis, Missouri, United States, 63136
      • Research Site 10001-156
    • Saint Louis, Missouri, United States, 63141
      • Research Site 10001-007
  • 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, 89121
      • Research Site 10001-124
    • Las Vegas, Nevada, United States, 89119
      • Research Site 10001-112
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Research Site 10001-060
    • Raritan, New Jersey, United States, 08869
      • 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, 45236
      • Research Site 10001-010
    • Cincinnati, Ohio, United States, 45246
      • Research Site 10001-134
    • Cincinnati, Ohio, United States, 45227
      • Research Site 10001-154
    • Columbus, Ohio, United States, 43212
      • Research Site 10001-014
    • Columbus, Ohio, United States, 43213
      • Research Site 10001-012
    • Dayton, Ohio, United States, 45419
      • Research Site 10001-141
    • Marion, Ohio, United States, 43302
      • Research Site 10001-148
  • Oklahoma
    • Edmond, Oklahoma, United States, 73003
      • Research Site 10001-017
  • 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
    • Spartanburg, South Carolina, United States, 29303
      • Research Site 10001-026
  • 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
  • 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
    • Fort Worth, Texas, United States, 76106
      • Research Site 10001-126
    • 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
    • Lubbock, Texas, United States, 79410
      • Research Site 10001-025
    • New Braunfels, Texas, United States, 78130
      • Research Site 10001-057
    • Powell, Texas, United States, 37849
      • Research Site 10001-106
    • 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
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female participants ≥18 years of age.
2. History of ASCVD (coronary heart disease [CHD], cardiovascular disease [CVD], or peripheral arterial disease [PAD]).
3. Serum LDL-C ≥1.8 millimole (mmol)/liter (L) (≥70 mg/dL).
4. Fasting triglyceride <4.52 mmol/L (<400 mg/dL) at screening.
5. Participants on statins should be receiving a maximally tolerated dose.
6. Participants not receiving statins must have documented evidence of intolerance to all doses of at least 2 different statins.
7. 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.

Exclusion Criteria:

1. New York Heart Association (NYHA) class IV heart failure.
2. Uncontrolled cardiac arrhythmia
3. Uncontrolled severe hypertension
4. Active liver disease

5. 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:

   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. Males who are unwilling to use an acceptable method of birth control during the entire study period (such as condom with spermicide).
7. Treatment with other investigational products or devices within 30 days or 5 half-lives of the screening visit, whichever is longer.
8. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Inclisiran; Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90, then every 6 months.	Drug: Inclisiran Sodium; Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
PLACEBO_COMPARATOR: Saline Solution; Placebo will be administered as a SC injection of saline solution on Day 1, Day 90, then every 6 months.	Drug: Placebo; Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).; Other Names: Saline Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in LDL-C From Baseline to Day 510		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	Baseline, Day 90 to Day 540

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510		Baseline, Day 510
Percentage Change in Total Cholesterol From Baseline to Day 510		Baseline, Day 510
Percentage Change in Apolipoprotein B (ApoB) From Baseline to Day 510		Baseline, Day 510
Percentage Change in Non-HDL-C From Baseline to Day 510		Baseline, Day 510
Absolute Change in LDL-C From Baseline to Day 510		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	Baseline, Day 90 to Day 540

Collaborators and Investigators

• Sponsor: The Medicines Company

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 21, 2017
• Primary Completion (ACTUAL): September 10, 2019
• Study Completion (ACTUAL): September 17, 2019

Study Registration Dates

• First Submitted: January 3, 2018
• First Submitted That Met QC Criteria: January 8, 2018
• First Posted (ACTUAL): January 16, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 5, 2020
• Last Update Submitted That Met QC Criteria: September 8, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: LDL-C; ASCVD; Inclisiran sodium
• Additional Relevant MeSH Terms: Vascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Cardiovascular Diseases; Hypercholesterolemia; Atherosclerosis
• Other Study ID Numbers: MDCO-PCS-17-04

Drug and device information, study documents

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