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

NCT ID: NCT03400800

Last Updated: 2020-08-21

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1617 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-01

Study Completion Date

2019-08-27

Brief Summary

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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

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Conditions

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ASCVD Risk Factor, Cardiovascular Elevated Cholesterol

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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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.

Group Type EXPERIMENTAL

Inclisiran Sodium

Intervention Type DRUG

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

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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Inclisiran Sodium

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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Saline Solution

Eligibility Criteria

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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. 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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Medicines Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ray Kausik, MD

Role: PRINCIPAL_INVESTIGATOR

Imperial College of London

Locations

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Research Site 11420-002

Chomutov, , Czechia

Site Status

Research Site 11420-003

Uherské Hradiště, , Czechia

Site Status

Research Site 11049-006

Berlin, , Germany

Site Status

Research Site 11049-002

Bochum, , Germany

Site Status

Research Site 11049-003

Frankfurt, , Germany

Site Status

Research Site 11049-007

Heidelberg, , Germany

Site Status

Research Site 11049-001

Leipzig, , Germany

Site Status

Research Site 11036-001

Budapest, , Hungary

Site Status

Research Site 11036-004

Debrecen, , Hungary

Site Status

Research Site 11036-002

Hatvan, , Hungary

Site Status

Research Site 11036-003

Zalaegerszeg, , Hungary

Site Status

Research Site 11048-018

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Site Status

Research Site 11048-016

Brzozów, Podkarpackie Voivodeship, Poland

Site Status

Research Site 11048-019

Ruda Śląska, Silesian Voivodeship, Poland

Site Status

Research Site 11048-011

Bydgoszcz, , Poland

Site Status

Research Site 11048-004

Gdansk, , Poland

Site Status

Research Site 11048-017

Gdansk, , Poland

Site Status

Research Site 11048-005

Gdynia, , Poland

Site Status

Research Site 11048-007

Katowice, , Poland

Site Status

Research Site 11048-012

Katowice, , Poland

Site Status

Research Site 11048-014

Krakow, , Poland

Site Status

Research Site 11048-003

Krakow, , Poland

Site Status

Research Site 11048-008

Lublin, , Poland

Site Status

Research Site 11048-001

Poznan, , Poland

Site Status

Research Site 11048-013

Rzeszów, , Poland

Site Status

Research Site 11048-015

Tarnów, , Poland

Site Status

Research Site 11048-009

Warsaw, , Poland

Site Status

Research Site 11048-006

Warszawice, , Poland

Site Status

Research Site 11048-002

Wroclaw, , Poland

Site Status

Research Site 11048-010

Wroclaw, , Poland

Site Status

Research Site 11027-003

Bloemfontein, Free State, South Africa

Site Status

Research Site 11027-005

Johannesburg, Gauteng, South Africa

Site Status

Research Site 11027-001

Cape Town, Western Cape, South Africa

Site Status

Research Site 11027-013

Cape Town, Western Cape, South Africa

Site Status

Research Site 11027-007

Kuils River, Western Cape, South Africa

Site Status

Research Site 11027-004

Somerset West, Western Cape, South Africa

Site Status

Research Site 11027-006

Pretoria, , South Africa

Site Status

Research Site 11027-011

Welkom, , South Africa

Site Status

Research Site - 11380-005

Cherkasy, , Ukraine

Site Status

Research Site - 11380-008

Kharkiv, , Ukraine

Site Status

Research Site - 11380-004

Kiev, , Ukraine

Site Status

Research Site - 11380-009

Kiev, , Ukraine

Site Status

Research Site - 11380-001

Kyiv, , Ukraine

Site Status

Research Site - 11380-002

Kyiv, , Ukraine

Site Status

Research Site - 11380-003

Kyiv, , Ukraine

Site Status

Research Site - 11380-007

Lviv, , Ukraine

Site Status

Research Site - 11380-006

Uzhhorod, , Ukraine

Site Status

Research Site - 11044-006

Edgbaston, Birmingham, United Kingdom

Site Status

Research Site - 11044-022

Sale, Cheshire, United Kingdom

Site Status

Research Site - 11044-023

Sale, Cheshire, United Kingdom

Site Status

Research Site - 11044-021

Timperley, Cheshire, United Kingdom

Site Status

Research Site - 11044-012

Liskeard, Cornwall, United Kingdom

Site Status

Research Site - 11044-009

Exeter, Devon, United Kingdom

Site Status

Research Site - 11044-019

Plymouth, Devon, United Kingdom

Site Status

Research Site - 11044-014

Chorley, Lancashire, United Kingdom

Site Status

Research Site - 11044-004

Waterloo, Liverpool, United Kingdom

Site Status

Research Site - 11044-027

Davyhulme, Manchester, United Kingdom

Site Status

Research Site - 11044-028

Bollington, , United Kingdom

Site Status

Research Site - 11044-026

Bury, , United Kingdom

Site Status

Research Site - 11044-007

Cardiff, , United Kingdom

Site Status

Research Site - 11044-024

Cheadle Hulme, , United Kingdom

Site Status

Research Site - 11044-010

Derby, , United Kingdom

Site Status

Research Site - 11044-001

Glasgow, , United Kingdom

Site Status

Research Site - 11044-008

Hexham, , United Kingdom

Site Status

Research Site - 11044-020

Macclesfield, , United Kingdom

Site Status

Research Site - 11044-025

Manchester, , United Kingdom

Site Status

Research Site - 11044-005

Manchester, , United Kingdom

Site Status

Research Site - 11044-029

Manchester, , United Kingdom

Site Status

Research Site - 11044-003

Reading, , United Kingdom

Site Status

Research Site - 11044-002

Stockton, , United Kingdom

Site Status

Countries

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Czechia Germany Hungary Poland South Africa Ukraine United Kingdom

References

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Wright RS, Ray KK, Landmesser U, Koenig W, Raal FJ, Leiter LA, Conde LG, Han J, Schwartz GG. Effects of Inclisiran in Patients With Atherosclerotic Cardiovascular Disease: A Pooled Analysis of the ORION-10 and ORION-11 Randomized Trials. Mayo Clin Proc. 2024 Jul 5:S0025-6196(24)00167-8. doi: 10.1016/j.mayocp.2024.03.025. Online ahead of print.

Reference Type DERIVED
PMID: 39093262 (View on PubMed)

Dutta S, Shah R, Singhal S, Singh S, Piparva K, Katoch CDS. A systematic review and meta-analysis of tolerability, cardiac safety and efficacy of inclisiran for the therapy of hyperlipidemic patients. Expert Opin Drug Saf. 2024 Feb;23(2):187-198. doi: 10.1080/14740338.2023.2293201. Epub 2023 Dec 19.

Reference Type DERIVED
PMID: 38063346 (View on PubMed)

Ray KK, Wright RS. Plain language summary of results from ORION-10 and ORION-11: two studies to learn how well inclisiran works in people with high cholesterol. Future Cardiol. 2023 Mar;19(4):175-184. doi: 10.2217/fca-2022-0133. Epub 2023 Jun 6.

Reference Type DERIVED
PMID: 37282500 (View on PubMed)

Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, Bisch JA, Richardson T, Jaros M, Wijngaard PLJ, Kastelein JJP; ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020 Apr 16;382(16):1507-1519. doi: 10.1056/NEJMoa1912387. Epub 2020 Mar 18.

Reference Type DERIVED
PMID: 32187462 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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MDCO-PCS-17-08

Identifier Type: -

Identifier Source: org_study_id

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