A Randomized Trial Assessing the Effects of Inclisiran on Clinical Outcomes Among People With Cardiovascular Disease

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

Sponsors

Lead Sponsor: University of Oxford

Collaborator: The Medicines Company
The TIMI Study Group

Source University of Oxford
Brief Summary

ORION-4 is a research study coordinated by the University of Oxford and co-sponsored by The University of Oxford and The Medicines Company. 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.

Detailed 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 55 years or older 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.

Overall Status Recruiting
Start Date October 30, 2018
Completion Date December 2049
Primary Completion Date December 2024
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of participants with a major adverse cardiovascular event Median follow-up of 5-years
Secondary Outcome
Measure Time Frame
Number of participants with a composite of CHD death or myocardial infarction Median follow-up of 5-years
Number of participants with cardiovascular death Median follow-up of 5-years
Enrollment 15000
Condition
Intervention

Intervention Type: Drug

Intervention Name: Inclisiran

Description: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.

Arm Group Label: Inclisiran

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).

Arm Group Label: Placebo

Other Name: Saline solution

Eligibility

Criteria:

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. 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.

Gender: All

Minimum Age: 55 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Overall Contact

Last Name: Louise Bowman

Phone: +44 (0)1865 743743

Email: [email protected]

Location
Facility: Status: Contact: CTSU, University of Oxford Louise Bowman
Location Countries

United Kingdom

Verification Date

November 2019

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Inclisiran

Type: Experimental

Description: Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection at randomization, 3 months and then every 6 months.

Label: Placebo

Type: Placebo Comparator

Description: Placebo will be administered as SC injections of saline solution at randomization, 3 months and then every 6 months.

Acronym ORION-4
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Prevention

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov