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

Overview

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.

Full Title of Study: “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)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Care Provider)
  • Study Primary Completion Date: September 10, 2019

Interventions

  • Drug: Inclisiran Sodium
    • Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
  • Drug: Placebo
    • Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).

Arms, Groups and Cohorts

  • Experimental: Inclisiran
    • Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90, then every 6 months.
  • Placebo Comparator: Saline Solution
    • Placebo will be administered as a SC injection of saline solution on Day 1, Day 90, then every 6 months.

Clinical Trial Outcome Measures

Primary Measures

  • Percentage Change in LDL-C From Baseline to Day 510
    • Time Frame: Baseline, Day 510
  • Time-adjusted Percentage Change in LDL-C Levels From Baseline After Day 90 and up to Day 540
    • Time Frame: Baseline, Day 90 to Day 540
    • Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 540 reported

Secondary Measures

  • 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
    • Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 540 reported
  • 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

Participating in This Clinical Trial

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 Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • The Medicines Company
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Scott Wright, MD, Principal Investigator, Mayo Clinic

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