Trial to Assess the Effect of Long Term Dosing of Inclisiran in Subjects With High CV Risk and Elevated LDL-C (ORION-8)
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|ClinicalTrials.gov Identifier: NCT03814187|
Recruitment Status : Completed
First Posted : January 23, 2019
Last Update Posted : March 7, 2023
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|Condition or disease||Intervention/treatment||Phase|
|ASCVD Elevated Cholesterol Heterozygous Familial Hypercholesterolemia Homozygous Familial Hypercholesterolemia||Drug: Inclisiran Sodium||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3275 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-label Extension Trial of the Phase III Lipid-lowering Trials to Assess the Effect of Long Term Dosing of Inclisiran Given as Subcutaneous Injections in Subjects With High Cardiovascular Risk and Elevated LDL-C|
|Actual Study Start Date :||April 16, 2019|
|Actual Primary Completion Date :||February 13, 2023|
|Actual Study Completion Date :||February 13, 2023|
Inclisiran sodium 300 milligrams (mg) will be administered as a single SC injection on Day 1*, 90, then every 180 days to Day 990.
*Subjects who received blinded placebo in the feeder study will receive blinded inclisiran and subjects who received blinded inclisiran in the feeder study will receive blinded placebo on Day 1 in ORION-8. Subjects from the open label ORION-3 study will not receive any injection of study drug on Day 1. Their first dose of study medication will be at day 90
Drug: Inclisiran Sodium
Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
- Percentage of subjects achieving prespecified LDL-C targets. [ Time Frame: Day 1080 ]A primary objective of the study is to evaluate the effect of inclisiran treatment on the proportion of subjects achieving prespecified LDL-C targets at end of study.
- Incidence of Adverse Events and Serious Adverse Events [ Time Frame: Baseline, Day 1080 ]Safety assessments include adverse events and serious adverse events for long-term safety profile
- Absolute and percentage change in LDL-C from baseline. [ Time Frame: Baseline, Day 1080 ]A secondary objective of this study is to evaluate the effect of inclisiran on LDL-C levels.
- Absolute and percentage change in other lipids and lipoprotein from baseline. [ Time Frame: Baseline, Day 1080 ]A secondary objective of this study is to evaluate the effect of inclisiran on other lipids and lipoproteins.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Completion on a previously qualifying inclisiran Phase II trial MDCO-PCS-16-01 (ORION-3), or Phase III lipid lowering ORION feeder study [MDCO-PCS-17-03 (ORION-9), MDCO-PCS-17-4 (ORION-10), or MDCO-PCS-17-08 (ORION-11)] meaning the subject received the last dose of study drug and completed the final study visit per applicable protocol.
- On current lipid-lowering therapies (such as a statin and/or ezetimibe) from previous study with no planned medication or dose change during study participation.
- Willing and able to give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures.
- 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 subject at significant risk [according to investigator's (or delegate's) judgment] if he/she participates in the clinical study.
- 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.
- Severe concomitant noncardiovascular disease that carries the risk of reducing life expectancy to less than 3 years,
- Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST), elevation >3x the upper limit of normal (ULN), or total bilirubin (TBIL) elevation >2x ULN at the last recorded visit in the feeder study prior to study entry visit.
Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least one method of acceptable effective contraception (eg, oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, 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.
- Planned use of other investigational medicinal products other than inclisiran or devices during the course of the study.
Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to:
- Subjects 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 subjects whose cooperation is doubtful due to drug abuse or alcohol dependency)
- Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (eg, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study)
- Have any medical or surgical condition, which in the opinion of the investigator would put the subject at increased risk from participating in the study
- Persons directly involved in the conduct of the study.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03814187
|Principal Investigator:||Scott Wright, MD||Mayo Clinic|
|Responsible Party:||Novartis Pharmaceuticals|
|Other Study ID Numbers:||
CKJX839A12306B ( Other Identifier: Novartis Pharmaceuticals )
2017-003092-55 ( EudraCT Number )
|First Posted:||January 23, 2019 Key Record Dates|
|Last Update Posted:||March 7, 2023|
|Last Verified:||March 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Hyperlipoproteinemia Type II
Homozygous Familial Hypercholesterolemia
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn