Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03705234
Other study ID # CTSU_MDCO_PCS-17-01
Secondary ID
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date October 30, 2018
Est. completion date December 2049

Study information

Verified date October 2023
Source University of Oxford
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

ORION-4 is a research study coordinated by the University of Oxford and co-sponsored by The University of Oxford and Novartis (Protocol: CTSU_MDCO-PCS-17-01 (CKJX839B12301)). The study aims to find out if a new cholesterol-lowering injection (inclisiran) safely lowers the risk of heart attacks and strokes in people who have already had one of these conditions, or who have had an operation or procedure to treat blocked arteries.


Description:

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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 16124
Est. completion date December 2049
Est. primary completion date July 2026
Accepts healthy volunteers No
Gender All
Age group 40 Years and older
Eligibility Inclusion Criteria 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 Exclusion Criteria 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Inclisiran
Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
Placebo
Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).

Locations

Country Name City State
United Kingdom CTSU, University of Oxford Oxford Oxfordshire
United States TIMI Study Group Boston Massachusetts

Sponsors (3)

Lead Sponsor Collaborator
University of Oxford Novartis Pharmaceuticals, The TIMI Study Group

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of participants with a major adverse cardiovascular event (MACE) 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.
Median follow-up of 5-years
Secondary Number of participants with MACE among those recorded to be taking high-intensity statin at baseline Median follow-up of 5-years
Secondary Number of participants with a composite of CHD death or myocardial infarction Median follow-up of 5-years
Secondary Number of participants with cardiovascular death Median follow-up of 5-years
See also
  Status Clinical Trial Phase
Recruiting NCT01572259 - Assessment of the Role of the Growth Hormone (GH) Onthe Intestinal Triglyceride-rich-lipoproteins (TRL) Metabolism Phase 3
Completed NCT05792787 - Association Between Apical Periodontitis and Atherosclerotic Cardiovascular Diseases
Completed NCT03911284 - The Learning Registry
Recruiting NCT06048588 - YN001 in Healthy Subjects and Patients With Coronary Atherosclerosis Phase 1/Phase 2
Completed NCT03096288 - Impact of Evolocumab on the Effects of Clopidogrel in Patients With High On-Treatment Platelet Reactivity Phase 4
Enrolling by invitation NCT05485961 - Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis Phase 2/Phase 3
Completed NCT01663402 - ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab Phase 3
Completed NCT03597412 - Rosuvastatin/Ezetimibe Versus Rosuvastatin in ASCVD Patients With Type 2 DM Phase 4
Completed NCT05974345 - In Silico Study Assessing the Impact of Inclisiran on Major Adverse Cardiovascular Events in Patients With Established Cardiovascular Disease
Active, not recruiting NCT05030428 - Study of Inclisiran to Prevent Cardiovascular (CV) Events in Participants With Established Cardiovascular Disease Phase 3
Completed NCT00185185 - Olmesartan Medoxomil in Atherosclerosis Phase 3
Completed NCT05129241 - Non-interventional Study on the Monthly Administration of 300 mg AliRocumab (PRALUENT®) With the 2 ml SYDNEY Auto-injector
Completed NCT02991118 - Evaluation of Long-Term Efficacy of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia at High Cardiovascular Risk Phase 3
Completed NCT05639244 - Time Restricted Eating and Innate Immunity N/A
Completed NCT02988115 - Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia and Statin Intolerant Phase 3
Recruiting NCT04215237 - How Atorvastatin Affects the Gut Flora and Metabolomics? N/A
Completed NCT05355402 - A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Adults With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease (Established or at Increased Risk for), and/or With Severe Hypertriglyceridemia Phase 2
Recruiting NCT05726838 - The Belgian REAL (BE.REAL) Registry
Active, not recruiting NCT04462159 - The Young Heart Study N/A
Not yet recruiting NCT03505073 - Association Between Dietary Habits and Risk Factors for Atherosclerotic Cardiovascular Diseases in Assiut Governorate

External Links