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

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)

Sponsors

Lead Sponsor: The Medicines Company

Source The Medicines Company
Brief 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). The study will be a multicenter study in the United States.

Overall Status Completed
Start Date December 21, 2017
Completion Date September 17, 2019
Primary Completion Date September 10, 2019
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure 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 Baseline, Day 90 to Day 540
Secondary Outcome
Measure Time Frame
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 Baseline, Day 90 to Day 540
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
Enrollment 1561
Condition
Intervention

Intervention Type: Drug

Intervention Name: Inclisiran Sodium

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

Arm Group Label: Inclisiran

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).

Arm Group Label: Saline Solution

Other Name: Saline Solution

Eligibility

Criteria:

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Scott Wright, MD Principal Investigator Mayo Clinic
Location
Facility:
Research Site 10001-015 | Birmingham, Alabama, 35211, United States
Research Site 10001-138 | Foley, Alabama, 36535, United States
Research Site 10001-113 | Huntsville, Alabama, 35801, United States
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Research Site 10001-013 | Chandler, Arizona, 85224, United States
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Research Site 10001-150 | Los Angeles, California, 90022, United States
Research Site 10001-043 | Northridge, California, 91324, United States
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Research Site 10001-033 | Sacramento, California, 95821-2134, United States
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Research Site 10001-044 | Torrance, California, 90502, United States
Research Site 10001-047 | Boca Raton, Florida, 33434, United States
Research Site 10001-084 | Clearwater, Florida, 33756, United States
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Research Site 10001-099 | Clearwater, Florida, 33761, United States
Research Site 10001-127 | Daytona Beach, Florida, 32117, United States
Research Site 10001-119 | Fleming Island, Florida, 32003, United States
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Research Site 10001-139 | Jacksonville, Florida, 32204, United States
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Research Site 10001-024 | Flint, Michigan, 48504, United States
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Location Countries

United States

Verification Date

September 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Inclisiran

Type: Experimental

Description: Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90, then every 6 months.

Label: Saline Solution

Type: Placebo Comparator

Description: Placebo will be administered as a SC injection of saline solution on Day 1, Day 90, then every 6 months.

Acronym ORION-10
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Care Provider)

Source: ClinicalTrials.gov