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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
Sponsor:
Information provided by (Responsible Party):
The Medicines Company

Study Description
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Brief Summary:
This is a Phase III, placebo-controlled, double-blind, randomized study in participants with ASCVD or ASCVD-Risk equivalents 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 an international multicenter study (non-United States).

Condition or disease Intervention/treatment Phase
ASCVD Risk Factor, Cardiovascular Elevated Cholesterol Drug: Inclisiran Sodium Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1617 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
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

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Inclisiran
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.
 Drug: Placebo
Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
Other Name: Saline Solution


Outcome Measures
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Primary Outcome Measures :
  1. Percentage Change in LDL-C From Baseline to Day 510 [ Time Frame: Baseline, Day 510 ]
  2. 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 ]

Secondary Outcome Measures :
  1. Absolute Change In LDL-C From Baseline To Day 510 [ Time Frame: Baseline, Day 510 ]
  2. 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 ]
  3. Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510 [ Time Frame: Baseline, Day 510 ]
  4. Percentage Change in Total Cholesterol From Baseline to Day 510 [ Time Frame: Baseline, Day 510 ]
  5. Percentage Change in Apolipoprotein B (ApoB) From Baseline to Day 510 [ Time Frame: Baseline, Day 510 ]
  6. Percentage Change in Non-HDL-C From Baseline to Day 510 [ Time Frame: Baseline, Day 510 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Participants may be included if they meet all of the following inclusion criteria prior to randomization:

  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. Calculated glomerular filtration rate >30 mL/min by estimated glomerular filtration rate (eGFR) using standardized clinical methodology
  6. Participants on statins should be receiving a maximally tolerated dose.
  7. Participants not receiving statins must have documented evidence of intolerance to all doses of at least 2 different statins.
  8. 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.
  9. 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

Exclusion Criteria:

Participants will be excluded from the study if any of the following exclusion criteria apply prior to randomization:

  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.

Contacts and Locations
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Information from the National Library of Medicine

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


Locations
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Sponsors and Collaborators
The Medicines Company
Investigators
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Principal Investigator: Ray Kausik, MD Imperial College of London
  Study Documents (Full-Text)

Documents provided by The Medicines Company:
Study Protocol  [PDF] January 31, 2019
Statistical Analysis Plan  [PDF] August 12, 2019

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT03400800    
Other Study ID Numbers: MDCO-PCS-17-08
First Posted: January 17, 2018    Key Record Dates
Results First Posted: August 21, 2020
Last Update Posted: August 21, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The Medicines Company:
Inclisiran sodium
ASCVD
LDL-C
Additional relevant MeSH terms:
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Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases