An Extension Trial of Inclisiran Compared to Evolocumab in Participants With Cardiovascular Disease and High Cholesterol

An Open Label, Active Comparator Extension Trial to Assess the Effect of Long Term Dosing of Inclisiran and Evolocumab Given as Subcutaneous Injections in Participants With High Cardiovascular Risk and Elevated LDL-C (ORION-3)

ClinicalTrials.gov Identifier: NCT03060577

Novartis Reference Number: MDCO-PCS-16-01

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

ORION-3 is a Phase II, open-label, non-randomized, active comparator extension trial to assess the efficacy, safety, and tolerability of long-term dosing of inclisiran and evolocumab given as subcutaneous injections in participants with high cardiovascular risk and elevated low-density lipoprotein cholesterol (LDL-C).

Condition 
Atherosclerotic Cardiovascular Disease
Symptomatic Atherosclerosis
Type2 Diabetes
Familial Hypercholesterolemia
Phase 
Phase 2
Overall status 
Active, not recruiting
Enrollment count 
490 participants
Start date 
Mar 24, 2017
Completion date 
Feb 28, 2022
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Inclisiran
Inclisiran is a synthetic, chemically modified small interfering ribonucleic acid (siRNA) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) messenger ribonucleic acid (mRNA) with a covalently attached triantennary N-acetylgalactosamine (GalNAc) ligand.
Drug
Evolocumab
Evolocumab is a fully human monoclonal antibody that inhibits PCSK9.

Eligibility Criteria

Inclusion Criteria:

Completion of Study MDCO-PCS-15-01 and no contraindication to receiving inclisiran or evolocumab.
Willing and able to give written and informed consent before initiation of any study related procedures and willing to comply with all required study procedures.
Willing to self-inject.

Exclusion Criteria:

Any uncontrolled or serious disease, or any medical or surgical condition that may either interfere with participation in the clinical study and/or put the participant at significant risk (according to investigator's [or delegate's] judgment).
An underlying known disease or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate), might interfere with interpretation of the clinical study results.
Serious comorbid disease in which the life expectancy of the participant is shorter than the duration of the trial (for example, acute systemic infection, cancer, or other serious illnesses).
Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver; unexplained alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation greater than 2 times upper limit of normal (ULN); or total bilirubin elevation greater than 1.5 times ULN at study entry visit.

Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least two methods of contraception (for example, oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device) for the entire duration of the study. Exemptions from this criterion are

Women >2 years postmenopausal (defined as 1 year or longer since their last menstrual period) AND more than 55 years of age
Postmenopausal women (as defined above) and less than 55 years old with a negative pregnancy test within 24 hours of enrollment
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 (that is, condom with spermicide).
Treatment with investigational medicinal products other than inclisiran or devices within 30 days or five half˗lives, whichever is longer.
Planned use of investigational medicinal products other than inclisiran or devices during the course of the study.
Participants with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients
Previous or current treatment (within 90 days of study entry) with monoclonal antibodies directed towards PCSK9.

Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to:

Inappropriate for this study, including participants who are unable to communicate or to cooperate with the investigator.
Unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study (including participants whose cooperation is doubtful due to drug abuse or alcohol dependency).
Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (for example, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study).
Involved with, or a relative of, someone directly involved in the conduct of the study.
Any known cognitive impairment (for example, Alzheimer's Disease).

Study Locations

United States
Jacksonville Center for Clinical Research
-
Jacksonville, 32216
Florida
United States
Midwest Institute For Clinical Research
-
Indianapolis, 46260
Indiana
United States
Mount Sinai Icahn School of Medicine
-
New York, 10029
New York
United States
Metabolic And Atherosclerosis Research Center
-
Cincinnati, 45227
Ohio
United States
Sterling Research Group
-
Cincinnati, 45246
Ohio
United States
Wellmont CVA Heart Institute
-
Greeneville, 37745
Tennessee
United States
Amarillo Heart Clinical Research Institute, Inc.
-
Amarillo, 79106
Texas
United States
National Clinical Research, Inc.
-
Richmond, 23294
Virginia
United States
Canada
St. Paul's Hospital
-
Vancouver, V6Z 1Y6
British Columbia
Canada
St. Boniface Hospital
-
Winnipeg, R2H 2A6
Manitoba
Canada
Eastern Regional Health Authority, Patient Research Centre
-
Saint John's, A1B 3V6
Newfoundland and Labrador
Canada
Brampton Research Associates
-
Brampton, L6Z 4N5
Ontario
Canada
Lawson Health Research Institute
-
London, N6A 5A5
Ontario
Canada
St. Michael's Hospital
-
Toronto, M5C 2T2
Ontario
Canada
ECOGENE-21 Clinical Trials Center
-
Chicoutimi, G7H 7K9
Quebec
Canada
Institut de Recherches Cliniques de Montreal
-
Montreal, H2W 1R7
Quebec
Canada
Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke (CIUSSS de l'Estrie - CHUS)
-
Sherbrooke, J1H 5N4
Quebec
Canada
Université Laval Quebec
-
Quebec, G1V 4G5
-
Canada
Clinique des maladies lipidique Quebec
-
Quebec, G1V 4W2
-
Canada
Germany
Medical University Berlin
-
Berlin, 12203
-
Germany
Medical Center Essen
-
Essen, 45355
-
Germany
University Hospital Frankfurt
-
Frankfurt, 60590
-
Germany
Medical University Hospital Heidelberg, Internal Medicine III
-
Heidelberg, 69120
-
Germany
Technical University Munich, German Heart Center
-
Munich, 80636
-
Germany
Netherlands
Amsterdam Medical Center
-
Amsterdam, 1105 AZ
-
Netherlands
Haga Hospital
-
Den Haag, 2545 CH
-
Netherlands
Deventer Ziekenhuis
-
Deventer, 7416 SE
-
Netherlands
Andromed Eindoven
-
Eindhoven, 5611 NV
-
Netherlands
Admiraal de Ruyter Hospital, Cardiology
-
Goes, 4462 RA
-
Netherlands
Bethesda Diabetes Research Center
-
Hoogeveen, 7909 AA
-
Netherlands
Medisch Centrum Gorecht
-
Hoogezand, 9603 AE
-
Netherlands
VOC Hoorn
-
Hoorn, 1624 NP
-
Netherlands
Leids Universitair Medisch Centrum (LUMC)
-
Leiden, 2333 ZA
-
Netherlands
Andromed Rotterdam
-
Rotterdam, 3039 BD
-
Netherlands
Diakonesseshuis, Vascular Policlinic
-
Utrecht, 3582 KE
-
Netherlands
UMC Utrecht
-
Utrecht, 3584 CX
-
Netherlands
VieCurie Venlo, Cardiology
-
Venlo, 5912 BL
-
Netherlands
Albert Schweitzer Hospital, Cardiology
-
Zwijndrecht, 3331 LZ
-
Netherlands
United Kingdom
Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust
-
Birmingham, B15 2TH
-
United Kingdom
Edinburgh Royal Infirmary
-
Edinburgh, EH16 4SA
-
United Kingdom
The Royal Devon and Exeter NHS Trust
-
Exeter, EX2 5DW
-
United Kingdom
Fowey River Practice
-
Fowey, PL23 1DT
-
United Kingdom
Buckinghamshire NHS Trust
-
High Wycombe, HP11 2TT
-
United Kingdom
Oak Tree Surgery
-
Liskeard, PL14 3XA
-
United Kingdom
Royal Free Hospital
-
London, NW3 2QG
-
United Kingdom
Central Manchester University Hospital NHS Foundation Trust
-
Manchester, M13 9WL
-
United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital
-
Newcastle upon Tyne, NE1 4LP
-
United Kingdom
The Alverton Practice
-
Penzance, TR18 4JH
-
United Kingdom
Knowle House Surgery
-
Plymouth, PL5 3JB
-
United Kingdom
Brannel Surgery
-
Saint Austell, PL26 7RL
-
United Kingdom
Rame Medical Ltd (Rame Research)
-
Torpoint, PL11 2TB
-
United Kingdom
Worcestershire Acute NHS Trust
-
Worcester, WR5 1DD
-
United Kingdom

Have a question?

Call 1-999-669-6682 or email [email protected]