Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol

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)

Sponsors

Lead Sponsor: The Medicines Company

Source 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).

Overall Status Completed
Start Date November 1, 2017
Completion Date August 27, 2019
Primary Completion Date July 31, 2019
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
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
Measure Time Frame
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
Enrollment 1617
Condition
Intervention

Intervention Type: Drug

Intervention Name: Inclisiran Sodium

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

Arm Group Label: Inclisiran

Intervention Type: Drug

Intervention Name: Placebo

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

Arm Group Label: Saline Solution

Other Name: Saline Solution

Eligibility

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Ray Kausik, MD Principal Investigator Imperial College of London
Location
Facility:
Research Site 11420-002 | Chomutov, 43001, Czechia
Research Site 11420-003 | Uherské Hradiště, 68601, Czechia
Research Site 11049-006 | Berlin, 12567, Germany
Research Site 11049-002 | Bochum, 44787, Germany
Research Site 11049-003 | Frankfurt, 60313, Germany
Research Site 11049-007 | Heidelberg, 69120, Germany
Research Site 11049-001 | Leipzig, 4103, Germany
Research Site 11036-001 | Budapest, 1036, Hungary
Research Site 11036-004 | Debrecen, 4025, Hungary
Research Site 11036-002 | Hatvan, 3000, Hungary
Research Site 11036-003 | Zalaegerszeg, 8900, Hungary
Research Site 11048-018 | Bydgoszcz, Kujawsko-pomorskie, 85-079, Poland
Research Site 11048-016 | Brzozów, Podkarpackie, 36-200, Poland
Research Site 11048-019 | Ruda Śląska, Slaskie, 41-709, Poland
Research Site 11048-011 | Bydgoszcz, 85-231, Poland
Research Site 11048-004 | Gdańsk, 80-382, Poland
Research Site 11048-017 | Gdańsk, 80-542, Poland
Research Site 11048-005 | Gdynia, 81-537, Poland
Research Site 11048-007 | Katowice, 04-040, Poland
Research Site 11048-012 | Katowice, 40-648, Poland
Research Site 11048-014 | Kraków, 31-216, Poland
Research Site 11048-003 | Kraków, 31-501, Poland
Research Site 11048-008 | Lublin, 20-709, Poland
Research Site 11048-001 | Poznań, 60-702, Poland
Research Site 11048-013 | Rzeszów, 35-055, Poland
Research Site 11048-015 | Tarnów, 33-100, Poland
Research Site 11048-009 | Warsaw, 04-628, Poland
Research Site 11048-006 | Warszawice, 01-192, Poland
Research Site 11048-002 | Wrocław, 50-381, Poland
Research Site 11048-010 | Wrocław, 51-314, Poland
Research Site 11027-003 | Bloemfontein, Free State, 9301, South Africa
Research Site 11027-005 | Johannesburg, Gauteng, 1619, South Africa
Research Site 11027-001 | Cape Town, Western Cape, 7500, South Africa
Research Site 11027-013 | Cape Town, Western Cape, 7646, South Africa
Research Site 11027-007 | Kuilsrivier, Western Cape, 7130, South Africa
Research Site 11027-004 | Somerset West, Western Cape, 7130, South Africa
Research Site 11027-006 | Pretoria, 184, South Africa
Research Site 11027-011 | Welkom, 9459, South Africa
Research Site - 11380-005 | Cherkasy, 18009, Ukraine
Research Site - 11380-008 | Kharkiv, 61444, Ukraine
Research Site - 11380-004 | Kiev, 3115, Ukraine
Research Site - 11380-009 | Kiev, 3115, Ukraine
Research Site - 11380-001 | Kyiv, 2002, Ukraine
Research Site - 11380-002 | Kyiv, 3037, Ukraine
Research Site - 11380-003 | Kyiv, 3049, Ukraine
Research Site - 11380-007 | Lviv, 79060, Ukraine
Research Site - 11380-006 | Uzhhorod, 8800, Ukraine
Research Site - 11044-006 | Edgbaston, Birmingham, B15 2SQ, United Kingdom
Research Site - 11044-022 | Sale, Cheshire, M33 2RH, United Kingdom
Research Site - 11044-023 | Sale, Cheshire, M33 4BR, United Kingdom
Research Site - 11044-021 | Timperley, Cheshire, WA14 5PF, United Kingdom
Research Site - 11044-012 | Liskeard, Cornwall, PL14 3XA, United Kingdom
Research Site - 11044-009 | Exeter, Devon, EX2 5DW, United Kingdom
Research Site - 11044-019 | Plymouth, Devon, PL5 3JB, United Kingdom
Research Site - 11044-014 | Chorley, Lancashire, PR7 7NA, United Kingdom
Research Site - 11044-004 | Waterloo, Liverpool, L22 0LG, United Kingdom
Research Site - 11044-027 | Davyhulme, Manchester, M41 7WJ, United Kingdom
Research Site - 11044-028 | Bollington, SK10 5JH, United Kingdom
Research Site - 11044-026 | Bury, BL9 ONJ, United Kingdom
Research Site - 11044-007 | Cardiff, CF15 9SS, United Kingdom
Research Site - 11044-024 | Cheadle Hulme, SK8 5LL, United Kingdom
Research Site - 11044-010 | Derby, S40 4AA, United Kingdom
Research Site - 11044-001 | Glasgow, G20 0SP, United Kingdom
Research Site - 11044-008 | Hexham, NE46 1QJ, United Kingdom
Research Site - 11044-020 | Macclesfield, SK11 6JL, United Kingdom
Research Site - 11044-025 | Manchester, M14 6WP, United Kingdom
Research Site - 11044-005 | Manchester, M15 6SX, United Kingdom
Research Site - 11044-029 | Manchester, M20 2RN, United Kingdom
Research Site - 11044-003 | Reading, RG2 0TG, United Kingdom
Research Site - 11044-002 | Stockton, TS19 8PE, United Kingdom
Location Countries

Czechia

Germany

Hungary

Poland

South Africa

Ukraine

United Kingdom

Verification Date

August 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Inclisiran

Type: Experimental

Description: 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.

Label: Saline Solution

Type: Placebo Comparator

Description: Placebo (1.5 mL) will be administered as a SC injection of saline solution on Day 1, Day 90, and then every 6 months.

Acronym ORION-11
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Care Provider)

Source: ClinicalTrials.gov