NCT03705234

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

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 16,124 (actual)
• Sponsor: University of Oxford · Academic / Other
• Sex: All
• Age: 40 Years
• Healthy volunteers: Not accepted

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.

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 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.

Conditions

• Atherosclerotic Cardiovascular Disease

Interventions

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

Timeline

• Start date: 2018-10-30
• Primary completion: 2026-10-01
• Completion: 2049-12-01
• First posted: 2018-10-15
• Last updated: 2025-12-11

Locations

2 sites across 2 countries: United States, United Kingdom

Regulatory

• FDA-regulated drug study