Atherosclerotic cardiovascular disease MedDRA version: 20.0 Level: LLT Classification code 10051615 Term: Atherosclerotic cardiovascular disease System Organ Class: 100000004866
Conditions
Sponsors
University of Oxford
The Medicines Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1) Age =55 years (2) History or evidence of at least one of the following: Myocardial infarction Ischaemic stroke Peripheral arterial disease (evident by lower extremity artery revascularization or aortic aneurysm repair) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7500 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7500
Exclusion criteria
Exclusion criteria: (1) Acute coronary syndrome or stroke less than 4 weeks before the Screening visit or during the Run-in period; (2) Coronary revascularization procedure planned within the next 6 months; (3) Known chronic liver disease; (4) Current or planned renal dialysis or transplantation; (5) Previous exposure to inclisiran or participation in a randomized trial of inclisiran; (6) Previous, current or planned treatment with a monoclonal antibody targeting PCSK9, or with a drug known to be contra-indicated with inclisiran; (7) Known to be poorly compliant with clinic visits or prescribed medication; (8) 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); (9) Women of child-bearing potential (unless using adequate contraception); or (10) Current participation in a clinical trial with an unlicensed drug or device. (11) Staff personnel directly involved with the study and any family member of the investigational study staff Those with a capillary blood point-of-care total cholesterol of less than 4 mmol/l at Screening will not be eligible to continue in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: The secondary objectives include the assessment of the effect of inclisiran on; (1) A composite of myocardial infarction (heart attack) or death from coronary disease (2) Cardiovascular death. ;Timepoint(s) of evaluation of this end point: The analysis will be undertaken at the end of the study after an average follow-up of 5 years and will include primary outcomes which have occurred during the scheduled follow-up period. ;Main Objective: The primary objective of ORION-4 is to determine the effect of inclisiran sodium, given 3 times in the first year and then 6 monthly for a total of around 5 years, on 'major adverse cardiovascular events' (defined as any occurrence of non-fatal myocardial infarction [heart attack], death from coronary disease, ischaemic stroke [stroke due to insufficient blood supply rather than bleeding] or urgent coronary revascularization procedure [angioplasty or bypass surgery]) during the scheduled treatment period. ;Primary end point(s): The primary assessment will involve an intention-to-treat comparison among all randomized participants of the effects of allocation to inclisiran versus placebo on time to first occurrence of major adverse cardiovascular events (MACE, defined as coronary heart disease death, myocardial infarction, fatal or non-fatal ischaemic stroke, or urgent coronary revascularization procedure) during the scheduled treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary assessments will involve intention-to-treat comparisons among all randomized participants of the effects of allocation to inclisiran versus placebo during the scheduled treatment period on time to first occurrence of: (i) The composite outcome of coronary heart disease death or myocardial infarction; and (ii) Cardiovascular death. ;Timepoint(s) of evaluation of this end point: The analysis will be undertaken at the end of the study after an average follow-up of 5 years and will include secondary outcomes which have occurred during the scheduled follow-up period. | — |
Countries
United Kingdom, United States
Outcome results
None listed