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

NCT03399370 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: MDCO-PCS-17-04
• Study Type: interventional
• Target: 1,561
• Locations: 1 country
• Sites: 145

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.

Conditions

ASCVD; Elevated Cholesterol

Keywords

Inclisiran sodium; ASCVD; LDL-C

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• 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

Study Arms (2)

Inclisiran

EXPERIMENTAL

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

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.

Drug: Placebo

Interventions

Inclisiran Sodium DRUG

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

Inclisiran

Placebo DRUG

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

Also known as: Saline Solution

Saline Solution

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• The Medicines Company: lead

Study Sites (145)

Research Site 10001-015

Birmingham, Alabama, 35211, United States

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Research Site 10001-138

Foley, Alabama, 36535, United States

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Research Site 10001-113

Huntsville, Alabama, 35801, United States

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Research Site 10001-058

Mobile, Alabama, 36608, United States

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Research Site 10001-037

Montgomery, Alabama, 36117, United States

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Research Site 10001-076

Saraland, Alabama, 36571, United States

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Research Site 10001-013

Chandler, Arizona, 85224, United States

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Research Site 10001-077

Mesa, Arizona, 85213, United States

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Research Site 10001-136

Phoenix, Arizona, 85014, United States

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Research Site 10001-051

Surprise, Arizona, 85374, United States

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Research Site 10001-019

Tucson, Arizona, 85712, United States

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Research Site 10001-004

Tucson, Arizona, 85741, United States

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Research Site 10001-132

Tucson, Arizona, 85745, United States

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Research Site 10001-073

Beverly Hills, California, 90211, United States

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Research Site 10001-050

Canoga Park, California, 91303, United States

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Research Site 10001-011

Carlsbad, California, 92008, United States

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Research Site 10001-065

El Cajon, California, 92020, United States

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Research Site 10001-150

Los Angeles, California, 90022, United States

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Research Site 10001-043

Northridge, California, 91324, United States

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Research Site 10001-022

Northridge, California, 91325, United States

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Research Site 10001-033

Sacramento, California, 95821-2134, United States

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Research Site 10001-105

San Ramon, California, 94582, United States

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Research Site 10001-008

Santa Rosa, California, 95405, United States

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Research Site 10001-153

Spring Valley, California, 91978, United States

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Research Site 10001-044

Torrance, California, 90502, United States

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Research Site 10001-047

Boca Raton, Florida, 33434, United States

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Research Site 10001-084

Clearwater, Florida, 33756, United States

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Research Site 10001-155

Clearwater, Florida, 33756, United States

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Research Site 10001-099

Clearwater, Florida, 33761, United States

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Research Site 10001-127

Daytona Beach, Florida, 32117, United States

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Research Site 10001-119

Fleming Island, Florida, 32003, United States

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Research Site 10001-070

Fort Lauderdale, Florida, 33308, United States

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Research Site 10001-067

Hialeah, Florida, 33012, United States

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Research Site 10001-139

Jacksonville, Florida, 32204, United States

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Research Site 10001-039

Jacksonville, Florida, 32216, United States

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Research Site 10001-098

Jacksonville, Florida, 32216, United States

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Research Site 10001-081

Miami, Florida, 33126, United States

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Research Site 10001-140

Miami, Florida, 33126, United States

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Research Site 10001-142

Miami, Florida, 33126, United States

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Research Site 10001-030

Miami, Florida, 33165, United States

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Research Site 10001-089

Miami, Florida, 33173, United States

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Research Site 10001-116

Miami, Florida, 33183, United States

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Research Site 10001-080

Miami Springs, Florida, 33166, United States

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Research Site 10001-027

Pembroke Pines, Florida, 33024, United States

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Research Site 10001-115

Pembroke Pines, Florida, 33027, United States

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Research Site 10001-048

Pembroke Pines, Florida, 33029, United States

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Research Site 10001-147

Pembroke Pines, Florida, 33029, United States

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Research Site 10001-003

Pinellas Park, Florida, 33781, United States

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Research Site 10001-104

Ponte Vedra, Florida, 32081, United States

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Research Site 10001-090

Saint Augustine, Florida, 32086, United States

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Research Site 10001-123

Sarasota, Florida, 34239-3513, United States

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Research Site 10001-102

St. Petersburg, Florida, 33713, United States

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Research Site 10001-038

Tampa, Florida, 33607, United States

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Research Site 10001-143

Tampa, Florida, 33614, United States

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Research Site 10001-069

Atlanta, Georgia, 30342, United States

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Research Site 10001-137

Dunwoody, Georgia, 30338, United States

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Research Site 10001-092

Macon, Georgia, 31210, United States

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Research Site 10001-059

Arlington Heights, Illinois, 60005, United States

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Research Site 10001-158

Chicago, Illinois, 60602, United States

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Research Site 10001-035

Chicago, Illinois, 60616, United States

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Research Site 10001-036

Evanston, Illinois, 60201, United States

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Research Site 10001-082

Indianapolis, Indiana, 46260, United States

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Research Site 1001-020

Sellersburg, Indiana, 47172, United States

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Research Site 10001-040

Valparaiso, Indiana, 46383, United States

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Research Site 10001-074

West Des Moines, Iowa, 50266, United States

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Research Site 10001-028

Hutchinson, Kansas, 67502, United States

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Research Site 10001-125

Lexington, Kentucky, 40503, United States

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Research Site 10001-108

Lexington, Kentucky, 40504, United States

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Research Site 10001-107

Owensboro, Kentucky, 42303, United States

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Research Site 10001-144

Crowley, Louisiana, 70526, United States

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Research Site 10001-041

Lake Charles, Louisiana, 70601, United States

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Research Site 10001-101

Monroe, Louisiana, 71201, United States

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Research Site 10001-024

Flint, Michigan, 48504, United States

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Research Site 10001-095

Grandville, Michigan, 49418, United States

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Research Site 10001-078

Sterling Heights, Michigan, 48310, United States

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Research Site 10001-034

Troy, Michigan, 48098, United States

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Research Site 10001-018

Edina, Minnesota, 55435, United States

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Research Site 10001-056

Saint Paul, Minnesota, 55102, United States

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Research Site 10001-156

St Louis, Missouri, 63136, United States

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Research Site 10001-007

St Louis, Missouri, 63141, United States

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Research Site 10001-053

Omaha, Nebraska, 68134, United States

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Research Site 10001-021

Omaha, Nebraska, 68144, United States

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Research Site 10001-112

Las Vegas, Nevada, 89119, United States

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Research Site 10001-124

Las Vegas, Nevada, 89121, United States

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Research Site 10001-060

Bridgewater, New Jersey, 08807, United States

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Research Site 10001-055

Raritan, New Jersey, 08869, United States

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Research Site 10001-054

Albany, New York, 12206, United States

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Research Site 10001-122

Binghamton, New York, 13901, United States

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Research Site 10001-128

Endwell, New York, 13760, United States

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Research Site 10001-042

New Windsor, New York, 12553, United States

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Research Site 10001-129

Poughkeepsie, New York, 12601, United States

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Research Site 10001-110

Williamsville, New York, 14221, United States

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Research Site 10001-063

Cary, North Carolina, 27518, United States

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Research Site 10001-064

Greensboro, North Carolina, 27401, United States

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Research Site 10001-145

Mooresville, North Carolina, 28117, United States

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Research Site 10001-046

Shelby, North Carolina, 28150, United States

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Research Site 10001-016

Akron, Ohio, 443311, United States

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Research Site 10001-120

Cincinnati, Ohio, 45219, United States

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Research Site 10001-154

Cincinnati, Ohio, 45227, United States

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Research Site 10001-010

Cincinnati, Ohio, 45236, United States

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Research Site 10001-134

Cincinnati, Ohio, 45246, United States

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Research Site 10001-014

Columbus, Ohio, 43212, United States

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Research Site 10001-012

Columbus, Ohio, 43213, United States

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Research Site 10001-141

Dayton, Ohio, 45419, United States

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Research Site 10001-148

Marion, Ohio, 43302, United States

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Research Site 10001-017

Edmond, Oklahoma, 73003, United States

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Research Site 10001-109

Wyomissing, Pennsylvania, 19610, United States

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Research Site 10001-001

Anderson, South Carolina, 29621, United States

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Research Site 10001-006

Greer, South Carolina, 29651, United States

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Research Site 10001-075.

Greer, South Carolina, 29651, United States

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Research Site 10001-111

Myrtle Beach, South Carolina, 29588, United States

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Research Site 10001-133

Pelzer, South Carolina, 29669, United States

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Research Site 10001-026

Spartanburg, South Carolina, 29303, United States

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Research Site 10001-103

Rapid City, South Dakota, 57701, United States

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Research Site 10001-146

Athens, Tennessee, 37303, United States

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Research Site 10001-130

Kingsport, Tennessee, 37660, United States

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Research Site 10001-118

Knoxville, Tennessee, 37909, United States

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Research Site 10001-100

Amarillo, Texas, 79106, United States

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Research Site 10001-087

Austin, Texas, 78726, United States

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Research Site 10001-117

Austin, Texas, 78756, United States

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Research Site 10001-009

Dallas, Texas, 75234, United States

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Research Site 10001-068

Edinburg, Texas, 78503, United States

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Research Site 10001-126

Fort Worth, Texas, 76106, United States

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Research Site 10001-031

Houston, Texas, 77002, United States

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Research Site 10001-088

Houston, Texas, 77024, United States

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Research Site 10001-091

Houston, Texas, 77027, United States

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Research Site 10001-061

Houston, Texas, 77058, United States

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Research Site 10001-032

Houston, Texas, 77070, United States

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Research Site 10001-025

Lubbock, Texas, 79410, United States

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Research Site 10001-057

New Braunfels, Texas, 78130, United States

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Research Site 10001-106

Powell, Texas, 37849, United States

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Research Site 10001-079

Round Rock, Texas, 78681, United States

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Research Site 10001-071

San Antonio, Texas, 78229, United States

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Research Site 10001-083

Schertz, Texas, 78154, United States

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Research Site 10001-149

Shavano Park, Texas, 78231, United States

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Research Site 10001-045

Tomball, Texas, 77375, United States

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Research Site 10001-005

Layton, Utah, 84041, United States

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Research Site 10001-002

Salt Lake City, Utah, 84123, United States

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Research Site 10001-052

Salt Lake City, Utah, 94107, United States

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Research Site 10001-093

Falls Church, Virginia, 22042, United States

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Research Site 10001-085

Manassas, Virginia, 20110, United States

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Research Site 10001-094

Midlothian, Virginia, 23114, United States

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Research Site 10001-023

Richmond, Virginia, 23294, United States

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Research Site 10001-029

Suffolk, Virginia, 23435, United States

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Research Site 10001-114

Tacoma, Washington, 98405, United States

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Related Publications (3)

• 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.

  PMID: 38063346 DERIVED

• 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.

  PMID: 37282500 DERIVED

• 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.

  PMID: 32187462 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Vice-President, Regulatory Operations
• Organization: The Medicines Company

frank.bosley@novartis.com

973-985-0597

Study Officials

• Scott Wright, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2018
• First Posted: January 16, 2018
• Study Start: December 21, 2017
• Primary Completion: September 10, 2019
• Study Completion: September 17, 2019
• Last Updated: October 5, 2020
• Results First Posted: October 5, 2020

Record last verified: 2020-09

Locations

US (145)