Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol
- Conditions
- ASCVDRisk Factor, CardiovascularElevated Cholesterol
- Interventions
- Drug: Placebo
- Registration Number
- NCT03400800
- Lead Sponsor
- The Medicines Company
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1617
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Inclisiran Inclisiran Sodium 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. Saline Solution Placebo Placebo (1.5 mL) will be administered as a SC injection of saline solution on Day 1, Day 90, and then every 6 months.
- Primary Outcome Measures
Name Time Method Percentage Change in LDL-C From Baseline to Day 510 Baseline, Day 510 Time-adjusted Percent Change in LDL-C Levels From Baseline After Day 90 and up to Day 540 Baseline, Day 90 to Day 540
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (70)
Research Site - 11044-027
🇬🇧Davyhulme, Manchester, United Kingdom
Research Site - 11044-009
🇬🇧Exeter, Devon, United Kingdom
Research Site 11027-003
🇿🇦Bloemfontein, Free State, South Africa
Research Site - 11044-012
🇬🇧Liskeard, Cornwall, United Kingdom
Research Site 11027-001
🇿🇦Cape Town, Western Cape, South Africa
Research Site 11027-004
🇿🇦Somerset West, Western Cape, South Africa
Research Site - 11044-006
🇬🇧Edgbaston, Birmingham, United Kingdom
Research Site - 11044-014
🇬🇧Chorley, Lancashire, United Kingdom
Research Site 11027-013
🇿🇦Cape Town, Western Cape, South Africa
Research Site 11049-006
🇩🇪Berlin, Germany
Research Site 11420-003
🇨🇿Uherské Hradiště, Czechia
Research Site 11049-002
🇩🇪Bochum, Germany
Research Site 11049-007
🇩🇪Heidelberg, Germany
Research Site 11049-003
🇩🇪Frankfurt, Germany
Research Site 11036-004
🇭🇺Debrecen, Hungary
Research Site 11049-001
🇩🇪Leipzig, Germany
Research Site 11036-001
🇭🇺Budapest, Hungary
Research Site 11036-002
🇭🇺Hatvan, Hungary
Research Site 11036-003
🇭🇺Zalaegerszeg, Hungary
Research Site 11048-019
🇵🇱Ruda Śląska, Slaskie, Poland
Research Site 11048-018
🇵🇱Bydgoszcz, Kujawsko-pomorskie, Poland
Research Site 11048-016
🇵🇱Brzozów, Podkarpackie, Poland
Research Site 11048-011
🇵🇱Bydgoszcz, Poland
Research Site 11048-004
🇵🇱Gdańsk, Poland
Research Site 11048-017
🇵🇱Gdańsk, Poland
Research Site 11048-007
🇵🇱Katowice, Poland
Research Site 11048-012
🇵🇱Katowice, Poland
Research Site 11048-014
🇵🇱Kraków, Poland
Research Site 11048-003
🇵🇱Kraków, Poland
Research Site 11048-001
🇵🇱Poznań, Poland
Research Site 11048-013
🇵🇱Rzeszów, Poland
Research Site 11048-015
🇵🇱Tarnów, Poland
Research Site 11048-009
🇵🇱Warsaw, Poland
Research Site 11048-006
🇵🇱Warszawice, Poland
Research Site 11048-002
🇵🇱Wrocław, Poland
Research Site - 11380-004
🇺🇦Kiev, Ukraine
Research Site 11027-011
🇿🇦Welkom, South Africa
Research Site 11048-010
🇵🇱Wrocław, Poland
Research Site 11027-005
🇿🇦Johannesburg, Gauteng, South Africa
Research Site 11027-006
🇿🇦Pretoria, South Africa
Research Site - 11380-008
🇺🇦Kharkiv, Ukraine
Research Site - 11380-005
🇺🇦Cherkasy, Ukraine
Research Site - 11380-009
🇺🇦Kiev, Ukraine
Research Site - 11380-003
🇺🇦Kyiv, Ukraine
Research Site - 11380-001
🇺🇦Kyiv, Ukraine
Research Site - 11380-002
🇺🇦Kyiv, Ukraine
Research Site - 11380-007
🇺🇦Lviv, Ukraine
Research Site - 11044-023
🇬🇧Sale, Cheshire, United Kingdom
Research Site - 11380-006
🇺🇦Uzhhorod, Ukraine
Research Site - 11044-022
🇬🇧Sale, Cheshire, United Kingdom
Research Site - 11044-007
🇬🇧Cardiff, United Kingdom
Research Site - 11044-004
🇬🇧Waterloo, Liverpool, United Kingdom
Research Site - 11044-024
🇬🇧Cheadle Hulme, United Kingdom
Research Site - 11044-026
🇬🇧Bury, United Kingdom
Research Site - 11044-028
🇬🇧Bollington, United Kingdom
Research Site - 11044-025
🇬🇧Manchester, United Kingdom
Research Site - 11044-001
🇬🇧Glasgow, United Kingdom
Research Site - 11044-008
🇬🇧Hexham, United Kingdom
Research Site - 11044-005
🇬🇧Manchester, United Kingdom
Research Site - 11044-029
🇬🇧Manchester, United Kingdom
Research Site - 11044-002
🇬🇧Stockton, United Kingdom
Research Site - 11044-003
🇬🇧Reading, United Kingdom
Research Site - 11044-020
🇬🇧Macclesfield, United Kingdom
Research Site 11420-002
🇨🇿Chomutov, Czechia
Research Site 11048-005
🇵🇱Gdynia, Poland
Research Site 11048-008
🇵🇱Lublin, Poland
Research Site 11027-007
🇿🇦Kuilsrivier, Western Cape, South Africa
Research Site - 11044-019
🇬🇧Plymouth, Devon, United Kingdom
Research Site - 11044-021
🇬🇧Timperley, Cheshire, United Kingdom
Research Site - 11044-010
🇬🇧Derby, United Kingdom