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

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ClinicalTrials.gov Identifier: NCT03705234
Recruitment Status : Recruiting
First Posted : October 15, 2018
Last Update Posted : March 25, 2019
Sponsor:
Collaborators:
The Medicines Company
The TIMI Study Group
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Atherosclerotic Cardiovascular Disease Drug: Inclisiran Drug: Placebo 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 150 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.


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Study Type : Interventional  (Clinical Trial)
Estimated 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 : October 30, 2018
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2049

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Atherosclerosis

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 Name: Saline solution




Primary Outcome Measures :
  1. Number of participants with a major adverse cardiovascular event [ Time Frame: Median follow-up of 5-years ]

    Defined as time to first occurrence 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 a composite of CHD death or myocardial infarction [ Time Frame: Median follow-up of 5-years ]
  2. Number of participants with cardiovascular death [ Time Frame: Median follow-up of 5-years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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, 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03705234


Contacts
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Contact: Louise Bowman +44 (0)1865 743743 orion4@ndph.ox.ac.uk
Contact: Marion Mafham +44 (0)1865 743743 orion4@ndph.ox.ac.uk

Locations
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United Kingdom
CTSU, University of Oxford Recruiting
Oxford, Oxfordshire, United Kingdom, OX3 7LF
Contact: Louise Bowman         
Sponsors and Collaborators
University of Oxford
The Medicines Company
The TIMI Study Group
Investigators
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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

Additional Information:
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Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT03705234     History of Changes
Other Study ID Numbers: CTSU_MDCO_PCS-17-01
First Posted: October 15, 2018    Key Record Dates
Last Update Posted: March 25, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Proposals for substudies must be approved by the Steering Committee. Procedure for accessing the data for this study are available on https://www.ndph.ox.ac.uk/about/data-access-policy
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: After the main study results have been announced and published
Access Criteria: See URL
URL: https://www.ndph.ox.ac.uk/about/data-access-policy

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Oxford:
Inclisiran
PCSK9
Cardiovascular
LDL Cholesterol
Cholesterol
Lipid
RNA interference
Additional relevant MeSH terms:
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Atherosclerosis
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases