Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol (ORION-11)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03400800|
Recruitment Status : Completed
First Posted : January 17, 2018
Results First Posted : August 21, 2020
Last Update Posted : August 21, 2020
- Study Details
- Tabular View
- Study Results
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|ASCVD Risk Factor, Cardiovascular Elevated Cholesterol||Drug: Inclisiran Sodium Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1617 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Care Provider)|
|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) or ACSVD Risk-Equivalents and Elevated Low-Density Lipoprotein Cholesterol (LDL-C)|
|Actual Study Start Date :||November 1, 2017|
|Actual Primary Completion Date :||July 31, 2019|
|Actual Study Completion Date :||August 27, 2019|
Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) in 1.5 milliliters (mL) will be administered as a SC injection on Day 1, Day 90, and then every 6 months.
Drug: Inclisiran Sodium
Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
Placebo Comparator: Saline Solution
Placebo (1.5 mL) will be administered as a SC injection of saline solution on Day 1, Day 90, and then every 6 months.
Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
Other Name: Saline Solution
- Percentage Change in LDL-C From Baseline to Day 510 [ Time Frame: Baseline, Day 510 ]
- Time-adjusted Percent Change in LDL-C Levels From Baseline After Day 90 and up to Day 540 [ Time Frame: Baseline, Day 90 to Day 540 ]
- 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 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Participants may be included if they meet all of the following inclusion criteria prior to randomization:
- 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.
- Calculated glomerular filtration rate >30 mL/min by estimated glomerular filtration rate (eGFR) using standardized clinical methodology
- 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.
- Subjects were willing and able to give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures
Participants will be excluded from the study if any of the following exclusion criteria apply prior to randomization:
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03400800
|Principal Investigator:||Ray Kausik, MD||Imperial College of London|
Documents provided by The Medicines Company:
|Responsible Party:||The Medicines Company|
|Other Study ID Numbers:||
|First Posted:||January 17, 2018 Key Record Dates|
|Results First Posted:||August 21, 2020|
|Last Update Posted:||August 21, 2020|
|Last Verified:||August 2020|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Lipid Metabolism Disorders