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

NCT03705234 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CTSU_MDCO_PCS-17-01ISRCTN88876914
• Study Type: interventional
• Target: 16,124
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Atherosclerotic Cardiovascular Disease

Keywords

Inclisiran; PCSK9; Cardiovascular; LDL Cholesterol; Cholesterol; Lipid; RNA interference

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Number of participants with MACE among those recorded to be taking high-intensity statin at baseline

  Median follow-up of 5-years

• 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

Study Arms (2)

Inclisiran

EXPERIMENTAL

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

Drug: Inclisiran

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Inclisiran DRUG

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

Inclisiran

Placebo DRUG

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

Also known as: Saline solution

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: collaborator
• University of Oxford: lead
• The TIMI Study Group: collaborator

Study Sites (2)

TIMI Study Group

Boston, Massachusetts, 02115, United States

Location

CTSU, University of Oxford

Oxford, Oxfordshire, OX3 7LF, United Kingdom

Location

Related Publications (1)

• Warden BA, Duell PB. Inclisiran: A Novel Agent for Lowering Apolipoprotein B-containing Lipoproteins. J Cardiovasc Pharmacol. 2021 Aug 1;78(2):e157-e174. doi: 10.1097/FJC.0000000000001053.

  PMID: 33990512 DERIVED

Related Links

• Study website

MeSH Terms

Conditions

Atherosclerosis

Interventions

ALN-PCS; Saline Solution

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Louise Bowman

  University of Oxford

  PRINCIPAL INVESTIGATOR

• Marion Mafham

  University of Oxford

  PRINCIPAL INVESTIGATOR

• David Preiss

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2018
• First Posted: October 15, 2018
• Study Start: October 30, 2018
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2049
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After the main study results have been announced and published
• Access Criteria: See URL

Locations

GB (1); US (1)