Phase III trial to assess long term effects of Inclisiran
Research type
Research Study
Full title
A long term 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(ORION 8).
IRAS ID
255663
Contact name
Manish Saxena
Contact email
Sponsor organisation
The Medicines Company
Eudract number
2017-003092-55
Clinicaltrials.gov Identifier
127589, IND
Duration of Study in the UK
3 years, 3 months, 0 days
Research summary
This study will be a long term extension study in up to 3700 subjects with atherosclerotic cardiovascular disease (ASCVD), ASCVD-risk equivalents (eg, diabetes and familial hypercholesterolemia), or heterozygous or homozygous familial hypercholesterolemia (HeFH or HoFH) and elevated low density lipoprotein cholesterol (LDL-C) despite maximum tolerated dose of LDL-C lowering therapies who have completed any of the following inclisiran Phase III lipid lowering studies: MDCO-PCS-17-03 (ORION-9), MDCO-PCS-17-04 (ORION-10), MDCO-PCS-17-08 (ORION-11) or MDCO-PCS-17-02 (ORION-5). The purpose of this extension study is to evaluate the efficacy, safety, and tolerability of long-term dosing of inclisiran. Informed consent will be obtained from subjects before the initiation of any study-specific procedures. The EOS visit in the previous study will be Day 1 in ORION-8.
Subjects completing one of the previously mentioned Phase III inclisiran studies (ORION-9, ORION-10, ORION-11 or ORION-5) and fulfilling all inclusion and exclusion criteria of this study will receive blinded inclisiran sodium 300 milligrams (mg) or blinded placebo on Day 1 in ORION-8. Subjects who received placebo in the previous feeder study will receive blinded inclisiran and subjects who received inclisiran in the previous feeder study will receive blinded placebo at this visit, in order to maintain the blinding of the feeder study until database lock of those studies. Subjects from the open label ORION-5 study will receive no drug administration on Day 1.
After first study drug administration, all subjects will be observed in the clinic for 30 minutes post injection before being discharged.
All subjects will return at Day 90 for the next visit and will receive open label inclisiran sodium 300 mg. Subjects will then return for open label drug administration of inclisiran sodium 300 mg every 180 days until EOS and be observed for 30 minutes at each visit.The duration of each subject is expected to be a maximum of 3 years (or until the investigator’s recommendation of discontinuation, sponsor's recommendation of discontinuation, the subject's decision to discontinue for any reason, until an administrative decision is made to end the study, or until inclisiran has received regulatory approval in the respective country, whichever occurs first). At this time, EOS evaluations will be conducted at the EOS visit.
REC name
London - Central Research Ethics Committee
REC reference
19/LO/0043
Date of REC Opinion
5 Feb 2019
REC opinion
Favourable Opinion