ORION-4: A Randomized Trial Assessing the Effects of Inclisiran on Clinical Outcomes Among People With Cardiovascular Disease

Sponsor
University of Oxford (Other)
Overall Status
Recruiting
CT.gov ID
NCT03705234
Collaborator
The TIMI Study Group (Other), Novartis Pharmaceuticals (Industry)
15,000
2
2
373.1
7500
20.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
15000 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
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
Actual Study Start Date :
Oct 30, 2018
Anticipated Primary Completion Date :
Jul 1, 2026
Anticipated Study Completion Date :
Dec 1, 2049

Arms and Interventions

Arm Intervention/Treatment
Experimental: Inclisiran

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

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

Placebo Comparator: Placebo

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

Drug: Placebo
Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
Other Names:
  • Saline solution
  • Outcome Measures

    Primary Outcome Measures

    1. Number of participants with a major adverse cardiovascular event (MACE) [Median follow-up of 5-years]

      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.

    Secondary Outcome Measures

    1. Number of participants with MACE among those recorded to be taking high-intensity statin at baseline [Median follow-up of 5-years]

    2. Number of participants with a composite of CHD death or myocardial infarction [Median follow-up of 5-years]

    3. Number of participants with cardiovascular death [Median follow-up of 5-years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    55 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 TIMI Study Group Boston Massachusetts United States 02115
    2 CTSU, University of Oxford Oxford Oxfordshire United Kingdom OX3 7LF

    Sponsors and Collaborators

    • University of Oxford
    • The TIMI Study Group
    • Novartis Pharmaceuticals

    Investigators

    • Principal Investigator: Louise Bowman, University of Oxford
    • Principal Investigator: Marion Mafham, University of Oxford
    • Principal Investigator: David Preiss, University of Oxford
    • Principal Investigator: Martin Landray, University of Oxford

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    University of Oxford
    ClinicalTrials.gov Identifier:
    NCT03705234
    Other Study ID Numbers:
    • CTSU_MDCO_PCS-17-01
    First Posted:
    Oct 15, 2018
    Last Update Posted:
    Mar 2, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by University of Oxford
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 2, 2022