A Randomized Trial Assessing the Effects of Inclisiran on Clinical Outcomes Among People With Cardiovascular Disease (ORION-4)
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|ClinicalTrials.gov Identifier: NCT03705234|
Recruitment Status : Recruiting
First Posted : October 15, 2018
Last Update Posted : September 16, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Atherosclerotic Cardiovascular Disease||Drug: Inclisiran Drug: Placebo||Phase 3|
The ORION-4 study aims to provide evidence about both the efficacy and safety of inclisiran. Inclisiran is a PCKS9 synthesis inhibitor which has been found to reduce LDL-cholesterol by about 50-60%. ORION-4 will investigate the effects of inclisiran on major adverse cardiovascular events.
The study is intended to be conducted at approximately 180 clinical sites in the UK and the USA. Approximately 15,000 participants aged 40 years or older for men, and 55 years or older for women, with pre-existing atherosclerotic cardiovascular disease will be randomized between inclisiran sodium 300 mg and matching placebo (given by subcutaneous injection on the day of randomization, at 3 months and then every 6-months) in a 1:1 ratio for a planned median duration of about 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15000 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||HPS-4/TIMI 65/ORION-4: A Double-blind Randomized Placebo-controlled Trial Assessing the Effects of Inclisiran on Clinical Outcomes Among People With Atherosclerotic Cardiovascular Disease|
|Actual Study Start Date :||October 30, 2018|
|Estimated Primary Completion Date :||July 2026|
|Estimated Study Completion Date :||December 2049|
Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection at randomization, 3 months and then every 6 months.
Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
Placebo Comparator: Placebo
Placebo will be administered as SC injections of saline solution at randomization, 3 months and then every 6 months.
Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
Other Name: Saline solution
- Number of participants with a major adverse cardiovascular event (MACE) [ Time Frame: Median follow-up of 5-years ]
Defined as time to first occurrence - during the scheduled treatment period - of:
- Coronary heart disease (CHD) death;
- Myocardial infarction;
- Fatal or non-fatal ischemic stroke; or
- Urgent coronary revascularization procedure.
- Number of participants with MACE among those recorded to be taking high-intensity statin at baseline [ Time Frame: Median follow-up of 5-years ]
- Number of participants with a composite of CHD death or myocardial infarction [ Time Frame: Median follow-up of 5-years ]
- Number of participants with cardiovascular death [ Time Frame: Median follow-up of 5-years ]
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:||40 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
History or evidence of at least one of the following:
- Prior MI; or
- Prior ischemic stroke; or
- Peripheral artery disease as evident by prior lower extremity artery revascularization or aortic aneurysm repair.
Minimum age is 40 years for men and 55 years for women
None of the following must be satisfied (based on self-reported medical history):
- Acute coronary syndrome or stroke less than 4 weeks before the Screening visit or during the Run-in period;
- Coronary revascularization procedure planned within the next 6 months;
- Known chronic liver disease;
- Current or planned renal dialysis or transplantation;
- Previous exposure to inclisiran or participation in a randomized trial of inclisiran;
- Previous (within about 3 months), current or planned treatment with a monoclonal antibody targeting PCSK9, or with a drug known to be contra-indicated with inclisiran (none currently known);
- Known to be poorly compliant with clinic visits or prescribed medication;
- Medical history that might limit the individual's ability to take trial treatments for the duration of the study (e.g. severe respiratory disease; cancer or evidence of spread within approximately the last 5 years, other than non-melanoma skin cancer; or history of alcohol or substance misuse) or may put the individual at significant risk in the opinion of the investigator (or their authorised deputy) if he/she were to participate in the trial;
- Women of child-bearing potential, current pregnancy, or lactation;
- Current participation in a clinical trial with an unlicensed drug or device; or
- Staff personnel directly involved with the study and any family member of the investigational study staff.
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): NCT03705234
|Contact: Louise Bowman||+44 (0)1865 firstname.lastname@example.org|
|Contact: Marion Mafham||+44 (0)1865 email@example.com|
|United States, Massachusetts|
|TIMI Study Group||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: David Morrow, MD, MPH 617-278-0145 TIMI@partners.org|
|Contact: Michelle O'Donoghue, MD, MPH 617-278-0145 TIMI@partners.org|
|CTSU, University of Oxford||Recruiting|
|Oxford, Oxfordshire, United Kingdom, OX3 7LF|
|Contact: Louise Bowman|
|Principal Investigator:||Louise Bowman||University of Oxford|
|Principal Investigator:||Marion Mafham||University of Oxford|
|Principal Investigator:||David Preiss||University of Oxford|
|Principal Investigator:||Martin Landray||University of Oxford|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||University of Oxford|
|Other Study ID Numbers:||
|First Posted:||October 15, 2018 Key Record Dates|
|Last Update Posted:||September 16, 2022|
|Last Verified:||September 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||Proposals for substudies must be approved by the Steering Committee. Procedure for accessing the data for this study are available on https://www.ndph.ox.ac.uk/data-access|
Statistical Analysis Plan (SAP)
|Time Frame:||After the main study results have been announced and published|
|Access Criteria:||See URL|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
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